[Show abstract][Hide abstract] ABSTRACT: ATP-binding cassette (ABC) transporters are associated with poor response to chemotherapy, and confer a poor prognosis in various malignancies. However, the association between the expression of the ABC sub-family G member 4 (ABCG4) and prognosis in patients with non-small-cell lung cancer (NSCLC) remains unclear. NSCLC tissue samples (n = 140) and normal lung tissue samples (n = 90) were resected from patients with stage II to IV NSCLC between May 2004 and May 2009. ABCG4 mRNA and protein expressions were detected by RT-PCR, western blot, and immunohistochemistry. Patients received four cycles of cisplatin-based post-surgery chemotherapy and were followed up until May 31st, 2014. ABCG4 positivity rate was higher in NSCLC than in normal lung tissues (48.6% vs. 0%, P<0.001) and ABCG4 expression was significantly associated with poor differentiation, higher tumor node metastasis (TNM) stage, and adenocarcinoma histological type (all P<0.001). Univariate (HR = 2.284, 95%CI: 1.570-3.324, P<0.001) and multivariate (HR = 2.236, 95%CI: 1.505-3.321, P<0.001) analyses showed that ABCG4 expression was an independent factor associated with a poor prognosis in NSCLC. Patients with ABCG4-positive NSCLC had shorter median survival than ABCG4-negative NSCLC (20.1 vs. 43.2 months, P<0.001). The prognostic significance of ABCG4 expression was apparent in stages III and IV NSCLC. In conclusion, high ABCG4 expression was associated with a poor prognosis in patients with NSCLC treated with cisplatin-based chemotherapy.
PLoS ONE 08/2015; 10(8):e0135576. DOI:10.1371/journal.pone.0135576 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.
Asian Pacific journal of cancer prevention: APJCP 09/2014; 15(17):7097-103. DOI:10.7314/APJCP.2014.15.17.7097 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The expression of novel oncogenic kinase (NOK), a member of the protein tyrosine kinase (PTK) family, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of NOK expression in NSCLC remains unclear.
In this study, NOK expression in tumor cells was assessed using immunohistochemical methods in 191 patients with resected NSCLC. The association of NOK expression with clinicopathological parameters, including the Ki-67 labeling index (LI), was also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of NOK expression on survival.
Data showed that NOK was expressed in 75.4% and 14.1% of cancer lesions and corresponding adjacent non-cancerous tissue, respectively. Out of all the clinicopathological factors analyzed, NOK expression was significantly correlated with the grade of tumor differentiation (P = 0.035), pTNM stage (P = 0.020), lymphatic metastasis (P = 0.005) and high Ki-67 LI (P < 0.001). NOK positive NSCLC patients had a significantly shorter survival time (P = 0.004, Log-rank test) and the prognostic significance of NOK expression was apparent in squamous cell carcinoma patients (P = 0.022). Multivariate analysis indicated that NOK expression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.731; P = 0.043).
Our results indicate that NOK expression is of clinical significance and can serve as a prognostic biomarker in NSCLC.
BMC Cancer 06/2014; 14(1):402. DOI:10.1186/1471-2407-14-402 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Olive oil-based lipid emulsion (LE) and medium chain triglyceride/long chain triglyceride (MCT/LCT) emulsion are both LEs with low ω-6 polyunsaturated fat acids (PUFAs) content. However, which one of these LEs is associated with a lower infection risk in patients receiving parenteral nutrition (PN) remains unclear. The aim of the study was to compare the effects of the two LEs in PN in esophageal cancer patients undergoing surgery.
Patients with resectable esophageal carcinoma were recruited and allocated randomly to two groups. The test group was given enteral nutrition (EN) with PN containing olive oil-based LE after tumor resection for ≥7 days, and the patients in the control group were supported by EN with MCT/LCT emulsion-based PN after surgery for the same time period. Immunological markers and inflammatory indicators were tested and perioperative clinical outcomes were determined. The trial was registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-13003562. 94 Patients were recruited, and grouped (olive oil-based LE, n=46 and MCT/LCT, n=48), matched for sex, age, body mass index, histological type, TNM stage, and nutrition risk screening (NRS) 2002 score.
There were no differences in perioperative fever (>38 °C), infectious complications, length of hospital stay (>14 days), length of critical care stay (>2 days), time for oral food intake, and in-hospital mortality between the two groups. The test group showed a higher increase in IgG level compared with the MCT/LCT group (p=0.028). There was no difference in other immunological markers and inflammatory indicators between the two groups.
PN containing olive oil-based or MCT/LCT LEs had similar effects on perioperative outcome, cell-mediated immune function and inflammatory response in esophageal cancer patients who had undergone surgery and were receiving EN.
[Show abstract][Hide abstract] ABSTRACT: The vascular structure related compression of esophagus is rather rare. Aberrant right subclavicular artery accounts for the majority of the rare entity, while the thoracic aorta aneurysm is a more dangerous type, called as dysphagia aortica. Delay in diagnosis and treatment of the dysphagia aortica predisposes to rupture and death. Herein, we reported a female patient with thoracic aorta aneurysm. A quick diagnosis by using chest contrast computed tomography (CT) scan and angiography of heart was made, and followed by emergent surgery. In the process, there was no delay on the diagnosis and treatment. The patient is going on well in the follow up.
[Show abstract][Hide abstract] ABSTRACT: Background:
Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice.
Materials and methods:
Sixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge.
Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1β and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues.
This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.
Journal of Surgical Research 11/2012; 182(2). DOI:10.1016/j.jss.2012.10.039 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To reproduce acute respiratory distress syndrome (ARDS) model in rabbit induced by chest blast injury and to analyze the pathogenesis and causes of early death in order to provide the basis for the early diagnosis of lung blast injury and its early warning system to facilitate an early treatment.
Sixty healthy New Zealand white rabbits were divided into six groups according to the different explosion distance with the random number table method. The survival rate and its resulting pathological changes were observed and patho physiological indexes and lung fluid content were determined at sequential time points post explosion.
Shock wave pressure less than 1 210.5 mm Hg (1 mm Hg=0.133 kPa, group A, B) resulted in limited injury to the lung within grade 2 as assessed with the abbreviated injury scale (AIS). The rabbits in these groups recovered soon and survived without any complication. Shock pressure higher than 2 036.1 mm Hg (group D, E) caused severe injuries to the lung, including deep laceration , disruption of lung hilus and large hematoma in the lung, and the injury severity of lungs was assessed above grade 5 as assessed with AIS. All rabbits died within 1 hour post explosion. The groups described above failed to meet the demand of an ARDS model for the present study. Shock wave pressure at 1 917.3 mm Hg (group C) produced extensive contusion from grade 4 to grade 5 as assessed with AIS. The rabbits survived in poor general condition, and arterial partial pressure of oxygen (PaO(2)) lowered within 6 hours . Pathological examination showed extensive and constant multi focal bleeding involving more than four lobes. The alveolar wall was edematous, with partial rupture and alveolar fusion in lung tissues was observed in the group C. Alveoli were filled with inflammatory cells, and hyaline membrane was formed occasionally . Compared with control group, the wet to dry weight ratio (W/D) in lungs increased obviously (6.46±0.24 vs. 3.98±0.19, P<0.01) in group C within 6 hours postinjury. The contents of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) were also increased distinctly compared with the control group [TNF-α (ng/L) in plasma: 328.89±6.26 vs. 62.12±2.98, TNF-α (ng/L) in BALF: 164.87±4.59 vs. 29.51±1.12; IL-6 (ng/L) in plasma: 128.51±4.13 vs. 19.32±1.53, IL-6 (ng/L) in BALF: 94.97±1.14 vs. 22.72±0.19, all P<0.05].
In an airtight environment, rabbit ARDS model can be reproduced successfully by blast injury with 1 917.3 mm Hg explosion pressure; TNF-α and IL-6 are involved in the pathogenesis and development of ARDS in blast injury. Pneumothorax as a result of lung rupture is the chief reason for early death and dysfunction of circulatory system is also an important reason in producing early death.
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 04/2011; 23(4):243-6.
[Show abstract][Hide abstract] ABSTRACT: Non-small cell lung cancer (NSCLC) cells are relatively resistant to ionizing radiation (IR). The phosphatidylinositol 3 (PI3) kinases are members of a family of lipid kinases that mediate cellular functions, including cell growth, proliferation and DNA repair, which may contribute to radioresistance. We studied whether inhibition of PI3 kinases could increase the response of NSCLC cells to γ-irradiation. The results showed that pretreatment of PI3 kinase inhibitor wortmannin dose-dependently radiosensitized NSCLC A549 and H1650 cells by inhibiting colony formation, which was due to enhanced G2/M arrest and apoptosis by wortmannin. The accelerated apoptosis was accompanied by increased loss of mitochondrial membrane potential (MMP) and cytochrome c release to the cytoplasm. In addition, wortmannin pretreatment significantly increased caspase-3 activation, which was associated with the repression of X-linked inhibitor of apoptosis protein (XIAP). The radio-sensitizing effect of wortmannin was correlated with the inhibition of phosphorylated PKB/Akt level. Furthermore, wortmannin down-regulated the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) which is involved in DNA double stand break (DSB) repair, as a result, leading to the inhibition of DSBs rejoining, as indicated by increased level of γ-H2AX at 24 h after IR. Taken together, our results demonstrate that wortmannin acts as a powerful radiosensitizer in NSCLC cells by inhibiting PI3K/Akt survival signaling and DNA repair protein DNA-PKcs, suggesting that PI3 kinase inhibitors may represent a novel strategy for overcoming resistance to IR-induced apoptosis in NSCLC cells.
[Show abstract][Hide abstract] ABSTRACT: The development and progression of esophageal cancer is associated with multiple alterations in the genome, including loss of the tumor suppressor phosphatase and tensin homolog deleted from the chromosome 10 (PTEN) gene. The purpose of this study was to determine the effects of adenovirus-mediated MMAC/PTEN expression on the growth and survival of human esophageal cancer cells in vitro and in vivo. We found that compared to control cells, overexpression of PTEN significantly suppressed growth and induced apoptosis in esophageal cancer cell lines Eca-109 and TE-1 via downregulation of Bcl-2 expression and changes in cell-cycle progression. Adenovirus PTEN also inhibited the growth of subcutaneous tumor xenografts by significantly reducing tumor size in vivo. Thus our results confirm the proposed functional role of MMAC/PTEN as a regulator of esophageal cancer progression in vivo and in vitro. PTEN might be an important biological marker and potential therapeutic target in the treatment of human esophageal cancer.
[Show abstract][Hide abstract] ABSTRACT: Roscovitine, a cyclin-dependent kinases (CDKs) inhibitor, has been reported to have anti-tumor effects in some cancer cell lines by inducing apoptosis. However, the exact underlying mechanisms are not fully understood. Here, we report that roscovitine induces expression and cleavage of the universal CDK inhibitor p21Waf1/Cip1 in non-small cell lung cancer (NSCLC) A549 cells in a dose-dependent manner. Western blots of roscovitine-treated cells undergoing apoptosis consistently demonstrated a 15 kDa band that was not detected in control cultures. CDK2 activity and PCNA expression were repressed with increasing dose of roscovitine. Accompanying these molecular changes was a progressive arrest of G2 phase and decreasing of 5-bromo-2-deoxyuridine (Brdu) incorporation of S phase cells. Caspase-3 inhibitor z-DEVD-fmk almost completely abolished roscovitine-induced apoptosis, as well as the appearance of 15 kDa band, indicating that p21Waf1/Cip1 cleavage was mediated by caspase-3 activity. Furthermore, this band was predominant in the floating apoptotic cells, while weakened in the adherent cells which were vital and pre-apoptotic. We also showed that roscovitine induced an enhanced expression of gamma-H2AX, which was blocked by caspase-3 inhibition, suggesting that p21Waf1/Cip1 cleavage may interfere with DNA repair, leading to increased frequency of double strand breaks (DSBs) and enhanced apoptosis. Here we show, for the first time, that p21Waf1/Cip1 cleavage, which is mediated by caspase-3 activity, is involved in roscovitine-induced apoptosis.
[Show abstract][Hide abstract] ABSTRACT: Roscovitine has been reported to have anti-proliferative properties and is in process of undergoing clinical trials. In addition to its intrinsic anticancer properties, it has recently been suggested that roscovitine may also enhance the activity of traditional chemo- and radio- therapies in certain cancer cell lines. The purpose of this study was to define the activity of roscovitine in increasing radiosensitivity of human non-small cell lung cancer (NSCLC) cell line A549 cells in vitro. A549 cells were exposed to ionizing radiation (IR) of gamma-ray with or without roscovitine pretreatment. Clonogenic assay was performed and cell cycle and apoptosis were analyzed by flow cytometry. Expression of PARP, Ku70 and Ku80 proteins was detected by Western blot. The active form of caspase-3 positive cells were measured by flow cytometry. Our results showed that roscovitine caused dose-dependent apoptosis in A549 cells. Pretreatment with minimally toxic concentration of roscovitine significantly radiosensitized A549 cells by inhibiting colony formation. We then examined potential mechanisms that may contribute to the enhanced radiation response induced by roscovitine. Our results showed that the combination treatment significantly induced apoptosis in A549 cells compared to roscovitine or IR treatment alone. Meanwhile, in the co-treatment group, the percentage of cells with the active form of caspase-3 was markedly increased, while roscovitine or IR alone had little effect. Roscovitine decreased S phase cells when used alone or in sequential combination with IR. Furthermore, this combination treatment blocked DNA repair process after IR, indicated by down regulation of Ku70 and Ku80 proteins, while the singly used treatment did not. Taken together, these results suggest that roscovitine has the potential to act as a radio-sensitizer in A549 cells by promoting caspase-3 activity and increasing apoptosis, affecting cell cycle distribution and impairing DNA repair process.
Journal of Radiation Research 09/2008; 49(5):541-8. DOI:10.1269/jrr.08024 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyze a 30-year historical series of patients treated in our hospital, who ingested corrosive substances, and to assess the effectiveness of surgical therapy administered in patients with strictures after caustic injury in esophagus during this period.
A total of 79 cases of caustic burns in esophagus were treated in Tangdu Hospital from 1971 to 2001. Their clinical and pathological data were reviewed, and collected from the medical records of patients and interviews with them.
More men (n = 61) than women (n = 18) ingested caustic substances with a sex ratio of 3.4:1 during the 30-year period. The caustic materials were liquid lye and acids (54 cases and 25 cases, respectively). Sixty-eight patients were given esophageal replacement in more than three months after caustic injury with no postoperative death, of which 17 cases developed postoperative complications making a complication rate of 25%. The most common one was cervical anastomotic leakage. All patients had improvement in swallowing afterwards.
The presence and severity of injuries are correlated with the amount of caustic substances ingested. Surgical treatment is a good option in patients with severe strictures, and colonic interposition might be the best surgical process. The most important factors to guarantee a successful outcome for surgery are good vascular supply and absence of tension in the anastomosis.
World Journal of Gastroenterology 11/2004; 10(19):2846-9. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the protective role of ischemic preconditioning (IPC) during lung ischemia-reperfusion (I/R) injury and its influence on inflammatory cytokine production.
In vivo I/R injury of rabbit was induced by blocking hilum of the left lung. The wet/dry ratio of the lung, lung permeability index and neutrophils percentage in bronchoalveolar lavage fluid (BALF) were detected as indexes of the lung injury. Serum levels of tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were also detected using enzyme-linked immunosorbent assay. The protective role of IPC and its influence on inflammatory cytokine production were observed.
The wet/dry ratio of the lung, lung permeability index and neutrophils percentage in BALF of I/R group were 9.73 +/- 1.14, (41.62 +/- 5.77) x 10(-4) and (58.1 +/- 10.0)% respectively. The IPC group indexes were 6.23 +/- 0.69, (20.31 +/- 4.03) x 10(-4) and (23.8 +/- 5.2)% respectively. There was a significant difference between the two groups (P < 0.01). Serum levels of TNFalpha, IL-6 and IL-8 of I/R group were (0.9078 +/- 0.1062), (0.2137 +/- 0.0598) and (0.7211 +/- 0.0979) ng/ml respectively. The IPC group indexes were (0.7478 +/- 0.0843), (0.1271 +/- 0.0089) and (0.5903 +/- 0.0746) ng/ml respectively, significantly lower than that of I/R group (P < 0.01).
Lung IPC has a marked protection effect against I/R injury. The effect was related to its inhibition of inflammatory cytokines such as TNFalpha, IL-6 and IL-8, thus reducing activation and infiltration of neutrophils.
Zhonghua wai ke za zhi [Chinese journal of surgery] 07/2003; 41(7):545-7.
[Show abstract][Hide abstract] ABSTRACT: To detect the factors relevant to stenosis of tracheal graft and to find feasible methods to solve this problem.
Sixteen mongrel dogs were divided into groups A and B randomly and equally. Five-ring-length tracheal segments were allotransplanted. All grafts and anastomotic sites were covered with omental pedicles. In group A, no immunosuppressant was given and in group B, the recipients were treated with cyclosporine. The animals were sacrificed 4 weeks after operation, and their postmortem specimens were examined grossly and histologically. All allografts were assessed by percent patency. Epithelial regeneration and morphology of the cartilage were semiquantitatively evaluated.
Structural integrity of the allografts were maintained better in group B than in group A. Tracheal stenosis was found to be more serious in group A. The scores of epithelial regeneration and cartilage morphology were higher in group B than in group A, and in each group positive correlation was found between the percent patency and the score of epithelial regeneration or cartilage morphology.
Immunosuppressive drugs are necessary to maintain the structure of allografts. Tracheal stenosis is correlated closely with epithelial regeneration and morphological maintenance of the cartilage.
Zhonghua wai ke za zhi [Chinese journal of surgery] 04/2003; 41(3):222-4.
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is necessary for the growth and metastasis of malignant tumor and is closely related to vascular endothelial growth factor (VEGF) and nitric oxide (NO). This investigation was aimed to detect the serum levels of VEGF and NO in squamous carcinoma patients and analyze the clinical significance for prognosis evaluation.
Serum VEGF and NO levels were detected by enzyme-linked immunosorbant assay (ELISA) and spectrophotometry, respectively, and their clinical significance was analyzed.
Serum levels of VEGF and NO in squamous carcinoma patients were significantly higher than that of in normal persons (P < 0.01). There was a positive correlation between serum VEGF, NO levels and tumor pathological phases, histological grades and lymph node metastasis (P < 0.01). There was also a positive correlation between serum VEGF level and serum NO level (P < 0.01).
Serum levels of VEGF and NO in squamous carcinoma patients were significantly correlated to the growth, development and malignant behavior of tumor and thus may serve as the indexes for clinical prognosis evaluation.
Ai zheng = Aizheng = Chinese journal of cancer 11/2002; 21(11):1248-50. · 2.16 Impact Factor