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ABSTRACT: Because of their important roles in mediating the stabilization and expression of p53, we hypothesized that high-risk genotypes of polymorphisms in p53-related genes, including p53, p73, p14(ARF), MDM2, and MDM4, may be associated with an increased risk of second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). We analyzed data from a cohort of 1,283 patients with index SCCHN who were recruited between 1995 and 2007 at MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for nine polymorphisms of p53-related genes. A log-rank test and Cox models were used to compare SPM-free survival and risk. Our results demonstrated that each p53-related polymorphism had a moderate effect on increased SPM risk, but when we combined risk genotypes of these nine polymorphisms together, we found that SPM-free survival was significantly shorter among risk groups with a greater number of combined risk genotypes. SPM risk increased with increasing number of risk genotypes (P< 0.0001 for trend). Compared with the low-risk group (0-3 combined risk genotypes), both the medium-risk (4-5 combined risk genotypes) and high-risk (6-9 combined risk genotypes) groups had significantly increased SPM risk (HR, 1.6; 95% CI, 1.0-2.6, and HR, 3.0; 95% CI, 1.8-5.0, respectively). Moreover, such significant associations were even higher in several subgroups. Our findings suggest that combined risk genotypes of p53-related genes may jointly modify SPM risk, especially in patients who are smokers and those with index non-oropharyngeal cancers. However, larger studies are needed to validate our findings.
Carcinogenesis 03/2013; · 5.70 Impact Factor
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ABSTRACT: The survivin gene is highly expressed in pancreatic cancer. The purpose of this study was to design and synthesize functionalized magnetic iron oxide nanoparticles (MNPs) targeting survivin gene for the detection of pancreatic cancer. The pancreatic cancer cell line BxPC-3 with survivin gene expression was selected in this study. The healthy lung fibroblast cell was used as a control. Chitosan-coated MNPs (CS@MNPs) and antisense oligodeoxynucleotide of survivin gene were conjugated to MNPs to give Sur-MNPs. Fourier transform infrared spectroscopy was performed to confirm the conjunction of chitosan. The interactions of MNPs, CS@MNPs, and Sur-MNPs in BxPC-3 cells were observed, recorded and analyzed. The size, morphology, cell uptake, cytotoxicity and stability of those particles were assessed by transmission electron microscope, Prussian blue staining, MTT assay and agarose gel electrophoresis. The magnetic resonance signal intensities of pancreatic cells labeled with CS@MNPs and MNPs, and Sur-MNPs, were compared on T(2) -weighted images. The results demonstrated that the level of cellular uptake of CS@MNPs was higher than that of naked MNPs. The Sur-MNPs had a suitable size (12 nm sized core), high stability, no cytotoxicity and good water dispersion. Sur-MNPs did not accumulate in healthy lung fibroblast cells, while being taken up by BxPC-3 cells. The Sur-MNPs in BxPC-3 cells could be visualized on T(2) -weighted images, which suggested that Sur-MNPs could be used to detect the expression of survivin gene. Thus, Sur-MNPs may be a potential molecular imaging probe targeting survivin gene for early detection of pancreatic cancer cells. Copyright © 2012 John Wiley & Sons, Ltd.
Contrast Media & Molecular Imaging 03/2013; 8(2):101-7. · 3.33 Impact Factor
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ABSTRACT: Genetically determinedcapacity for NER may modulate both cancer risk and prognosis. Thus, we evaluated associations of seven selected variants in the NER core genes with recurrence risk in 658SCCOP patients treated principally by radiation. The sevenpolymorphisms in the core NERgenes (XPC-rs2228000, XPC-rs2228001, XPD-rs1799793, XPD-rs13181, XPG-rs17655, ERCC1-rs3212986, and XPA-rs1800975)were genotyped using PCR-RFLP methodand log-rank test and multivariable Cox models were used to evaluate the associationsin both dominant and recessive genetic models. In a dominant model, we found that polymorphisms of XPC-rs2228000,XPD-rs1799793, and XPG-rs17655were significantly associated with disease-free survival(log-rank,P =0.014; P = 0.00008; and P = 0.0007, respectively),and these polymorphisms were significantly associated with recurrence risk of SCCOP (HR = 1.6, 95% CI, 1.1-2.3 for XPC-rs2228000; HR =0.4, 95%, 0.3-0.6 for XPD-rs1799793; and HR =0.5, 95% CI, 0.4-0.8 for XPG-rs17655)after multivariable adjustment. Moreover, the borderline significant or significant associations were also found for these three polymorphisms in HPV16/18-positive SCCOP patients (HR= 1.6, 95% CI, 1.0-4.1 for XPC-rs2228000; HR = 0.2, 95%, 0.1-0.5 for XPD-rs1799793; and HR = 0.1, 95% CI, 0.0-0.9 for XPG-rs17655). However, similarly significant associations were not found for these polymorphisms in a recessive model. These findings suggest that polymorphisms of XPC-rs2228000,XPD-rs1799793, and XPG-rs17655in the NER core genes may contribute to recurrence risk of SCCOP, particularly HPV-positive SCCOP, in a dominant but not in a recessive model. However, validation of these results is warranted.
International Journal of Cancer 01/2013; · 5.44 Impact Factor
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ABSTRACT: Both and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition, affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that polymorphisms modify the association between HPV16 seropositivity and OSCC risk.
Four single-nucleotide polymorphisms in were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models.
Overall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9-1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8-5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3-9.4). Similar results were found for rs2292832, rs11614913, and rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers.
Our results indicate that polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings.
PLoS ONE 01/2013; 8(2):e56622. · 4.09 Impact Factor
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ABSTRACT: Lymphatic vessels in primary tumor tissue play an important role in lymphatic metastasis. Lymphatic metastasis of malignant neoplasms is significantly related to prognosis, influencing both recurrence and survival. The aim of this study was to investigate the correlation of intra-tumoral lymphatic vessel density (iLVD) and peri-tumoral lymphatic vessel density (pLVD) with biological behavior and prognostic parameters in pancreatic carcinoma (PC) and other pancreatic tumors. Lymphangiogenesis was examined using the D2-40 monoclonal antibody in 33 cases of PC, 7 neuroendocrine tumors of the pancreas (NETP), 7 solid pseudopapillary tumors of the pancreas (SPTP) and 3 cystadenomas of the pancreas (CP). Positively-stained microvessels were counted at magnification x400 in dense lymphatic vascular foci (hotspots). The LVD of PC was compared to 3 other pancreatic tumors. The relationships among the LVD, the extent of differentiation, lymphatic invasion, lymph node metastasis and other clinicopathological parameters of PC were analyzed. There was no difference in the iLVD among PC, NETP, SPTP and CP. The pLVD of NETP was markedly higher than that of PC, SPTP and CP. The pLVD of PC was significantly higher than that of SPTP and CP, but there was no difference between SPTP and CP. The pLVD of PC was significantly associated with the extent of differentiation, lymphatic invasion and lymph node metastasis, whereas it was not associated with age, gender, tumor size, tumor location and peri-pancreatic invasion. The iLVD of PC was not correlated with these clinicopathological parameters. There was no difference in iLVD and no marked difference in pLVD among the pancreatic tumors. Detection of pLVD is of greater importance than detecting iLVD in these pancreatic tumors, as pLVD can be utilized for the prediction of lymph node metastasis, thus aiding in the evaluation of patient prognosis.
Molecular Medicine Reports 04/2012; 5(4):959-63. · 0.42 Impact Factor
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ABSTRACT: Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).
A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.
We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (Ptrend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6).
These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.
Molecular Cancer 03/2012; 11:17. · 3.99 Impact Factor
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ABSTRACT: p53 and p73 interact with human papillomavirus (HPV) E6 and E7 oncoproteins. The interplay between p53 and p73 and HPV16 may lead to deregulation of cell cycle and apoptosis, through which inflammation/immune responses control the HPV clearance and escape of immune surveillance, and subsequently contribute to tumor HPV16 status. In this case-case comparison study, HPV16 status in tumor specimens was analyzed and p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms were genotyped using genomic DNA from blood of 309 oropharyngeal cancer patients. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in univariate and multivariable logistic regression models to examine the association. The results from this study showed both p53 variant genotypes (Arg/Pro+Pro/Pro) and p73 variant genotypes (GC/AT+AT/AT) were significantly associated with HPV16-positive tumor in oropharyngeal cancer patients (OR, 1.9, 95% CI, 1.1-3.3 and OR, 2.1, 95% CI, 1.2-3.8, respectively), while the combined variant genotypes (p53 Pro carriers and p73 AT carriers) exhibited a significantly greater association with HPV16-positive tumor (OR, 3.2, 95% CI, 1.4-7.4), compared with combined wild-type genotypes (p53 Arg/Arg and p73 GC/GC), and the association was in a statistically significant dose-effect relationship (p = 0.001). Moreover, such association was more pronounced among several subgroups. These findings suggest that variant genotypes of p53 and p73 genes may be individually, or more likely jointly, associated with tumor HPV16-positive oropharyngeal cancer patients, particularly in never smokers. Identification of such susceptible biomarkers would greatly influence on individualized treatment for an improved prognosis.
PLoS ONE 01/2012; 7(4):e35522. · 4.09 Impact Factor
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ABSTRACT: Increased plasma free fatty acid (FFA) level is a hallmark of type 2 diabetes. However, the underlying molecular basis for FFA-caused hyperglycemia remains unclear. Here we identified plasma 5'-adenosine monophosphate (pAMP) markedly elevated in the plasma of type 2 diabetic mice. High levels of FFAs induced damage in vein endothelial cells and contributed to an increase in pAMP. Administration of synthetic 5'-AMP caused hyperglycemia and impaired insulin action in lean wild-type mice. 5'-AMP elevated blood glucose in mice deficient in adenosine receptors with equal efficiency as wild-type mice. The function of pAMP was initiated by the elevation of cellular adenosine levels, directly stimulating G-6-Pase enzyme activity, attenuating insulin-dependent GLUT4 translocation in skeletal muscle, and displaying a rapid and steep increase in blood glucose and a decrease in hepatic glycogen level. It was followed by an increase in the gene expression of hepatic Foxo1 and its targeting gene Pepck and G6Pase, which was similar to diabetic phenotype in db/db mice. Our results suggest that pAMP is a potential upstream regulator of hyperglycemia in type 2 diabetes.
AJP Endocrinology and Metabolism 11/2011; 302(3):E325-33. · 4.75 Impact Factor
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ABSTRACT: To explore the role of polymorphisms of p53-related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16-associated oral cancer in a case-control study with 325 cases and 335 cancer-free controls. We found that HPV16 seropositivity alone was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6]. After combining genotypes of seven polymorphisms and using the low-risk group (0-3 combined risk genotypes) and HPV16 seronegativity as the reference group, the medium-risk (4 combined risk genotypes) and high-risk groups (5-7 combined risk genotypes) and HPV16 seronegativity were associated with only an OR of 1.6 (95% CI, 1.1-2.5) and 1.2 (95% CI, 0.7-1.9) for oral cancer risk, respectively, whereas the low-risk, medium-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.1 (95% CI, 1.2-3.6), 4.0 (95% CI, 1.8-9.1) and 19.1 (95% CI, 5.7-64.2), respectively. Notably, such effect modification by these combined risk genotypes was particularly pronounced in young subjects (aged < 50 years), never smokers and patients with oropharyngeal cancer. Taken together, these findings suggest that the combined risk genotypes of p53-related genes may modify risk of HPV16-associated oral cancer, especially in young patients, never-smokers and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.
International Journal of Cancer 11/2011; 131(3):E251-8. · 5.44 Impact Factor
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ABSTRACT: Carbon tetrachloride (CCl(4) ) is a well-established model for screening hepato-protective drugs. The aim of the present study was to evaluate the potential protective effects of a novel soluble β-glucan salecan on acute liver injury induced by CCl(4) in mice and to further explore the underlying mechanisms. Mice were given salecan (40 mg kg(-1) ) or phosphate-buffered saline for 3 days prior to treatment with a single intraperitoneal dose of CCl(4) (1 ml kg(-1) body weight). Animals were sacrificed at 0, 12, 24, 48, 72 and 96 h post-injection of CCl(4) . Serum liver enzyme levels, histology, lipid peroxidation, glutathione (GSH) content, expression of antioxidant enzymes and hepatocyte proliferation were subsequently evaluated. The serum levels of hepatic enzyme markers were markedly reduced in the salecan pretreatment group compared with the control group. Histopathological examination of the livers revealed that hepatocellular degeneration and necrosis were significantly attenuated at an early stage during CCl(4) intoxication and liver recovery was markedly accelerated at a later stage in salecan pre-administered mice. Furthermore, salecan administration remarkably alleviated lipid peroxidation and restored GSH depletion. Meanwhile, the expression of antioxidant genes was significantly elevated in the salecan-treated group. Interestingly, the administration of salecan remarkably enhanced hepatocyte proliferation in the recovery phase after CCl(4) injection. Taken together, these results demonstrated that salecan exhibits a protective action on acute hepatic injury induced by CCl(4) through attenuating oxidative stress and accelerating hepatocyte regeneration.
Journal of Applied Toxicology 07/2011; 32(10):796-803. · 2.48 Impact Factor
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ABSTRACT: This investigation was designed to determine the effect of a novel soluble beta-glucan salecan on acute alcohol-induced hepatic injury in mice. Mice were given salecan (15 or 30 mg/kg) or PBS for 4 d. Ethanol (6 g/kg) was administered orally 1 h after the last injection. The animals were sacrificed at 10 h after alcohol administration. Pretreatment with salecan significantly ameliorated the hepatic damage induced by ethanol, as evidenced by markedly reduced serum aminotransferase activities and hepatocyte steatosis. Salecan administration remarkably alleviated the formation of thiobarbituric acid-reactive substances and counteracted glutathione depletion. The mRNA level of peroxisome proliferator activated receptor alpha, a major gene responsible for fatty acid oxidation, was significantly increased after salecan pretreatment. The expression of diacylglycerol acyltransferase 1, an important gene responsible for triacylglycerol synthesis, was markedly decreased after salecan was administrated. These findings suggest that salecan might represent a novel protective strategy against alcoholic liver injury.
Bioscience Biotechnology and Biochemistry 01/2011; 75(10):1990-3. · 1.28 Impact Factor
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ABSTRACT: Increasing evidence from behavioral and neuroimaging studies suggests that mesial temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain function. However, the alteration of coherent neural activities in such a default-mode network (DMN) in mTLE has yet to be investigated. The present study analyzed the resting-state functional MRI data from two groups of mTLE patients with left and right hippocampal sclerosis using independent component analysis. In comparison with healthy controls, decreased functional connectivity in the dorsal mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was observed in these two patient groups. Moreover, the right but not left mTLE patients showed bilaterally decreased functional connectivity in the mesial temporal lobe and increased functional connectivity in the posterior cingulate cortex. The decreased functional connectivity of the mesial temporal lobe was related to the epilepsy duration, suggesting that the posterior cingulate cortex may play a compensatory role for the altered DMN in the right mTLE. These findings indicate that the DMN is widely affected even if a single network node is impaired. An extensive regional overlap between the DMN and the previously described epileptic network suggests that the widespread functional impairments in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN between the left and right mTLE support a view that there are different pathological mechanisms underlying these two types of epilepsies.
Brain research 04/2010; 1323:152-60. · 2.46 Impact Factor
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ABSTRACT: Temporarily pulmonary hilum clamping is available for the trauma surgeon to deal with serious pulmonary injuries, but the physiologic influence needs further evaluation. This study was to establish a temporary pulmonary hilum clamping model for thoracic damage-control surgery and determine the safety time latitude of this manipulation.
After anesthetized and catheter instrumented, the left pulmonary hilus of pigs were clamped with a urethral catheter after thoracotomy maintained for three different time period, 90 minutes (C90), 120 minutes (C120), and 150 minutes (C150), and then unclamped. Hemodynamic data were recorded and serum samples were collected for d-dimer detection and other hematology analysis, as well as 1 cm3 pulmonary tissue was obtained for histologic study before clamping, at the end of clamping, and at 0.5, 1, 1.5, 2, and 4 hours after unclamping.
There were 100% of C90, 83.3% of C120, and 33.3% of C150 pigs survived. Animals of C150 group suffered highest blood pressure and heart rate, respiratory index, pulmonary dynamic compliance, and cardiac output. Pulmonary vascular resistance, platelet count, and D-dimer showed minor significant changes between C90 and C120 groups, whereas a marked changes in C150 animals during the study. There were much more serious histologic changes in C150 group compared with C90 and C120 groups.
We established a pulmonary hilum clamping animal model for pulmonary damage investigation. It was determined that 120 minutes was the longest safety time for hilum clamping without lethal pulmonary injury in porcine.
The Journal of trauma 04/2010; 68(4):810-7. · 2.48 Impact Factor
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ABSTRACT: An experimental model of cardiopulmonary bypass in rats with pulmonary hypertension is necessary to understand underlying mechanisms and develop protective strategies. Male Sprague-Dawley rats were randomly divided into a sham group, cardiopulmonary bypass group, pulmonary hypertension group, and pulmonary hypertension with cardiopulmonary bypass group. Both groups with pulmonary hypertension received a subcutaneous injection of monocrotaline 60 mg x kg(-1) on day 0. Cardiopulmonary bypass was instituted in one of them 21 days later. The sham and pulmonary hypertension control groups underwent cannulation only. Cardiopulmonary bypass was conducted for 60 min at a flow rate of 100 mL x kg(-1) x min(-1). Hemodynamic investigations, blood gas analysis, interleukin-6, tumor necrosis factor-alpha, and survival studies were performed subsequently. Time-dependent increases of serum interleukin-6 and tumor necrosis factor-alpha were found after cardiopulmonary bypass in both groups. This model allows the study of multiple organ pathophysiological processes after cardiopulmonary bypass in rats with pulmonary hypertension, as well as the evaluation of possible protective strategies.
Asian cardiovascular & thoracic annals 07/2009; 17(3):285-90.
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ABSTRACT: To establish a temporary pulmonary hilum clamping model for thoracic damage control surgery, as well as to determine the safety time latitude of this manipulation.
Pigs were anaesthetised and instrumented with a thermodilution cardiac output catheter. The left pulmonary hilum was clamped with a urethral catheter after thoracotomy, maintained for three different time periods (n=6 for each group), 90min (C90), 120min (C120) and 150min (C150) and then unclamped. Haemodynamic data were recorded and the serum samples were collected for D-dimer detection and other haematological analysis. A 1-cm(3) pulmonary tissue of the left lower lobe was also obtained for histological study before clamping, at the end of clamping and at 0.5, 1, 1.5, 2 and 4h after unclamping.
Postoperative survival rate in each group of the pigs was as follows: 100% (all six) of C90, 83.3% (five of six) of C120, and 33.3% (two of six) of C150. Blood pressure (BP) and heart rate (HR) increased after clamping and gradually declined after unclamping. The animals of C150 group suffered highest BP and HR, respiratory index, pulmonary dynamic compliance and cardiac output. Platelet count showed no significant changes between the C90 and C120 groups, whereas a decline was noticed in the C150 group. Pulmonary vascular resistance increased significantly after pulmonary hilum clamping; when unclamped, there were minor changes in animals of C90 and C120 groups while there was a persistent elevation in the C150 group. An elevated D-dimer was detected in the C150 group, whereas it was normal in the C90 and C120 groups. There was significantly serious inflammatory cell infiltration, perivascular oedema and haemorrhagic infiltration in the C150 group compared with the C90 and C120 groups.
We established a pulmonary hilum clamping animal model for investigating pulmonary damage. By studying the haemodynamic and lung function changes of three different unilateral pulmonary hilum clamping time, it was determined that 120min was the longest safety time for hilum clamping without lethal pulmonary injury in porcine models.
Injury 07/2009; 40(9):956-62. · 1.98 Impact Factor
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ABSTRACT: The detection of circulating nucleic acids has long been explored for the diagnosis of a variety of clinical conditions. The aim of this study was to detect the cell-free mRNA expression of BIRC5 in patients with effusions and assess its potential diagnostic value. Pleural fluids and ascites samples were collected prospectively from 112 patients. The cell-free RNA was extracted from effusions and the mRNA expression of BIRC5 was detected using real-time RT-PCR. The expression of carcinoembryonic antigen (CEA) and biochemical markers in effusions was also assayed. Effusions were classified as benign or malignant on the basis of their definitive pathologic or cytologic diagnoses. The expression of cell-free BIRC5 mRNA was statistically significantly higher in the malignant group than in the benign group. BIRC5 mRNA was also significantly different between patients with Stage III and Stage IV non-small cell lung cancers. The sensitivity and diagnostic accuracy of BIRC5 were 79.0 and 81.3%, whereas a combination of CEA and BIRC5 reached 86.4% sensitivity and 88.4% accuracy. These results indicate that effusions with higher levels of cell-free BIRC5 mRNA are more likely to be malignant. Determination of BIRC5 and CEA in effusions could enhance diagnostic value in the diagnosis of malignant effusions.
International Journal of Cancer 05/2009; 125(8):1921-5. · 5.44 Impact Factor
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ABSTRACT: Acute renal dysfunction is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to evaluate the potential protective effect of melatonin on CPB-induced renal damage in a rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: sham, control (CPB + placebo), low dose of melatonin (CPB + 10 mg/kg melatonin) and high dose of melatonin (CPB + 20 mg/kg melatonin). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2, 3, and 24 hr postoperation. Serum creatinine and blood urea nitrogen levels were assayed. Rats were killed 24 hr after surgery, the histologic appearance of the kidney and malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) contents were determined. The expression levels of hemeoxygenase-1 (HO-1) protein and gene were determined using western blotting and real-time PCR, respectively. In the control group, CPB surgery significantly increased urea, creatinine levels in serum, MDA and MPO levels in tissues, while decreasing SOD and CAT activities in tissues. Histopathologic findings of the control group confirmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. These changes were markedly reversed in both low dose of melatonin and high dose of melatonin groups. Furthermore, HO-1 gene transcript and protein were significantly upregulated in the kidney tissues after melatonin treatment compared with the placebo treatment. Our findings show that melatonin was effective in preventing CPB-induced renal damage probably through its antioxidant function and upregulation of HO-1.
Journal of Pineal Research 05/2009; 46(3):248-54. · 5.79 Impact Factor
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ABSTRACT: An increasing number of patients were undergoing cardiac surgery with cardiopulmonary bypass (CPB) and more attention had been paid to hepatic injury after CPB. This study was designed to study how CPB could induce and aggravate the hepatic injury in a rat model. Male Sprague-Dawley rats were randomly divided into two groups (n=12): sham and CPB groups. Blood samples were collected at the beginning, at the cessation of CPB, and at 0.5, 1, 2, 3 and 24 h post-operation. Liver samples were harvested at 24 h after operation. In CPB group, the levels of serum liver enzymes and tumor necrosis factor-alpha, activities of inducible nitric oxide synthase, malondialdehyde and myeloperoxidase in liver tissue were significantly increased. In addition, swollen hepatocytes, vacuolization and congestion in sinusoids were observed. On the contrary, the activities of liver antioxidative enzymes and the concentration of glutathione (GSH) decreased remarkably. All results indicated that CPB would induce and aggravate hepatic injury by facilitating oxidative stress and the systemic inflammatory response.
Interactive cardiovascular and thoracic surgery 03/2008; 7(1):18-22.
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ABSTRACT: Accumulating evidence reveals that statins possess direct anti-inflammatory properties through inhibition of proinflammatory cytokine and chemokine secretion in addition to their antioxidant effects, which may contribute to amelioration of ischemia-reperfusion injury. This study tested the hypothesis that perioperative treatment of simvastatin suppresses the cardiac isograft ischemia-reperfusion injury by down-regulation of CC chemokine receptor-2 expression in an inbred rat model of cardiac transplantation.
Donor hearts from Lewis rats were heterotopically transplanted to Lewis rat recipients. Recipients were orally treated with simvastatin (1 mg/kg) or vehicle every morning 3 days before the surgery until the harvest day. Rats were killed at 6 hours and at 1, 3, and 7 days after transplantation. Injury was assessed by infarct size measurement, histologic and immunohistochemical examination, and intragraft myeloperoxidase activity assay. Monocyte chemoattractant protein-1 levels in serum and graft were analyzed by enzyme-linked immunosorbent assay, and intragraft CC chemokine receptor-2 expression was measured by quantitative real-time polymerase chain reaction.
The infarct size and macrophage infiltration were all significantly reduced in the simvastatin-treated group compared with those of the control group at 1 day after transplantation. Neutrophil accumulation was significantly suppressed until 3 days after transplantation, whereas myeloperoxidase activity had been significantly diminished at 1 day after transplantation. Both monocyte chemoattractant protein-1 concentrations in serum and graft were remarkably decreased at 6 hours after transplantation. Intragraft CC chemokine receptor-2 expression was also down-regulated at 1 day and 3 days after transplantation.
Perioperative treatment of simvastatin could suppress the isograft ischemia-reperfusion injury through retarding intragraft monocyte chemoattractant protein-1 accumulation and CC chemokine receptor-2 expression.
The Journal of thoracic and cardiovascular surgery 10/2007; 134(3):780-8. · 3.41 Impact Factor
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ABSTRACT: To evaluate the diagnosis value of integrated positron emission tomography and computed tomography (PET/CT) with lung masses, this study emphasized the correlation between tumor size and maximum standardized uptake value (SUVmax) in selected regions of interest (ROI) of lung masses.
A retrospective analysis was performed on 85 patients with solid pulmonary lesions, all verified by pathology. The morphology, edge (speculated margins and lobule), size, density of pulmonary masses, and on-chest CT images were reviewed. The SUVmax in ROI of pulmonary masses was calculated.
Among the 85 patients with lung masses, 59 patients presented with pulmonary malignant neoplasm and 26 patients with benign lesions. The sensitivity, specificity, and accuracy were 89.8%, 61.5%, 81.2%, respectively, for PET measurement only, 88.1%, 65.4%, 81.2% for CT only, and 96.6%, 80.8%, 91.8% for PET/CT. The size of pulmonary malignant neoplasm in the 59 patients was apparently correlated with the ROI's SUVmax (r=0.617, P<.001). However, the size of pulmonary benign mass in the 26 patients was not correlated with the SUVmax.
PET/CT is of greater value in characterization of lung masses than PET and CT performed separately. The examination of lung tumor can be further specified by the correlation between the size of pulmonary malignant neoplasm and the ROI's SUVmax.
International Journal of Biomedical Imaging 01/2007; 2007:17131.