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Radiation-induced heart disease (RIHD) is a serious side effect of radiotherapy for thoracic tumors. Advanced myocardial fibrosis in the late phase of RIHD can lead to myocardial remodeling, heart function impairing and heart failure, resulting in serious clinical consequences, and its pathogenesis remains vague. DNA methylation is one of the important epigenetic mechanisms which often occurs in response to environmental stimuli and is crucial in regulating gene expression. We hypothesized DNA methylation may contribute to pathogenesis in radiation-induced heart fibrosis (RIHF) and altered DNA methylation patterns probably influenced the genes expression in RIHF. In present study, we found genome-wide differences in DNA methylation status and RNA expression were demonstrated and we screened out 44 genes whose altered expression maybe were regulated by CpG island methylation within the gene promoter in RIHF of Sprague-Dawley rat by employing gene expression arrays and human CpG island microarrays. Gene expression and CpG island methylation levels of several candidate genes were further validated. Our investigation provided a new dimension to reveal the specific mechanisms of RIHF and explore the potential therapeutic targets for it.

Haze is one of the major factors that degrade outdoor images, and dehazing becomes an important issue in many applications. In order to address the problems of being unsmooth and the absence of neighbor information for the transmission estimation under Dark Channel Prior (DCP) framework, we proposed a new improved method using Kernel Regression Model (KRM) on local neighbor data. Firstly, the initial transmission in atmospheric light model is estimated by DCP. Secondly, the transmission is refined according to KRM. Experimental results on synthetic and real images show that our method can address this problem and has better dehazing results than several state-of-the-art methods.

Accurate and reliable assessment of chlorophyll-a (Chl-a) concentration in turbid waters by remote sensing is challenging due to optical complexity of case II waters. Recently, an optimization procedure based on minimizing root mean square error (RMSE) with three-band model was suggested to retrieve the Chl-a concentration in the Pearl River Estuary (PRE) in China. However, it is sensitive to initial values of model parameters and it doesn’t consider other two bands information to determine each optimal band. To estimate the Chl-a concentration according to information of all bands without initial values, we proposed an optimization procedure based on maximizing correlation of the Chl-a concentration in situ and the Chl-a concentration estimated. Firstly, correlations are computed with the three-band model, in which each band varies from the minimal value to the maximal value. Secondly, the sum of correlations for all values of other two bands is computed to find the optimal value for the first band. Lastly, the sum of correlations for all values of other one band with the first optimal band is computed to find the second and third optimal bands. The calibrated three-band model is applied to retrieve the Chl-a concentration from the reflectance data in the PRE on May 16, 2008. RMSE and correlation indices of our method and two state-of-the-art methods in this dataset are shown the effectiveness of our method. These findings imply that the extensive database of remote sensing could be used to quantitatively monitor the Chl-a concentration in the PRE.

To evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) and to investigate the association of the status of KRAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome.Twenty-eight patients with advanced NSCLC were enrolled in this single center, uncontrolled pilot clinical study. All the patients developed drug resistance or disease progression after first-line chemotherapy of either a docetaxel + cisplatin regimen or a vinorelbine + cisplatin regimen and then received nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy. Eight cases were stage IIIB and 20 were stage IV. An i.v. dosage regimen of 200 mg of nimotuzumab was given as a single dose, injected into the patient at days 1, 8 and 15; i.v. gemcitabine was injected at a dose of 1000 mg/mIn total, 28 patients with advanced NSCLC received 101 therapeutic cycles. The mean cycle number was 3.6. Median time to progression was 4.9 (2.5-6.5) months; median overall survival and 1-year survival rate were 9.8 months and 48.5%, respectively. There was one case of complete response, six cases of partial response, 11 cases of stable disease and 10 cases of progressive disease. Response rate was 25%, and clinical benefit rate was 64.3%. Major toxic reactions were bone marrow suppression and gastrointestinal reaction. Only one patient developed grade I acneiform eruption.Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced NSCLC was active and well-tolerated in this setting. Patients with EGFR amplification and KRAS gene wild type had a better prognosis. Prospective, randomized, controlled, large-scale clinical studies are needed to confirm the results.

Clustering gene expression data are an important problem in bioinformatics because understanding which genes behave similarly can lead to the discovery of important biological information. Many clustering methods have been used in the field of gene clustering. This paper proposed a new method for gene expression data clustering based on an improved expectation maximization(EM) method of multivariate Gaussian mixture models. To solve the problem of over-reliance on the initialization, we propose a remove and add initialization for the classical EM, and make a random perturbation on the solution before continuing EM iterations. The number of clusters is estimated with the Quasi Akaike’s information criterion in this paper. The improved EM method is tested and compared with some other clustering methods; the performance of our clustering algorithm has been extensively compared over several simulated and real gene expression data sets. Our results indicated that improved EM clustering method is superior than other clustering algorithms and can be widely used for gene clustering.

Kernel density estimators (KDE) used for many medical image applications only consider the intensity information of each pixel or its neighbors without the ability of expressing the structure and shape of tissues and organs, and they suffer from boundary bias problem. In this paper, we propose a new first-order kernel density estimation (FOKDE) method for 1D intensity information and 2D spatial information of medical image in two steps. First, the FOKDE of intensity information is estimated and applied to medical image segmentation with the multi-thresholding algorithm. Second, we estimate the FOKDE of spatial information on the initial segmentation, which can express the structure and shape of organs and tissues. In order to evaluate the FOKDE and KDE of the 2D spatial information, we apply them to medical image segmentation with the hill-climbing strategy. Density estimation experiments and segmentation application results on the simulated dataset and real abdomen CT images show us that the FOKDE has smaller boundary bias than the KDE, and that it can estimate the structure and shape of tissues and organs with spatial information effectively.

Clustering gene expression data is an important research topic in bioinformatics because knowing which genes act similarly can lead to the discovery of important biological information. Many clustering algorithms have been used in the field of gene clustering. The multivariate Gaussian mixture distribution function was frequently used as the component of the finite mixture model for clustering, however the clustering cannot be restricted to the normal distribution in the real dataset. In order to make the cluster algorithm strong adaptability, this paper proposes a new scheme for clustering gene expression data based on the multivariate elliptical contoured mixture models (MECMMs). To solve the problem of over-reliance on the initialization, we propose an improved expectation maximization (EM) algorithm by adding and deleting initial value for the classical EM algorithm, and the number of clusters can be treated as a known parameter and inferred with the QAIC criterion. The improved EM algorithm based on the MECMMs is tested and compared with some other clustering algorithms, the performance of our clustering algorithm has been extensively compared over several simulated and real gene expression datasets. Our results indicated that improved EM clustering algorithm is superior to the classical EM algorithm and the support vector machines (SVMs) algorithm, and can be widely used for gene clustering.

An important but difficult problem of Gaussian mixture models (GMM) for medical image analysis is estimating and testing the number of components by model selection criterion. There are many available methods to estimate the k based on likelihood function. However, some of them need the maximum number of components is known as priori and data is usually over-fitted by them when log-likelihood function is far larger than penalty function. We investigate the log-characteristic function of the GMM to estimate the number of models adaptively for medical image. Our method defines the sum of weighted real parts of all log-characteristic functions of the GMM as a new convergent function and model selection criterion. Our new model criterion makes use of the stability of the sum of weighted real parts of all log-characteristic functions of the GMM when the number of components is larger than the true number of components. The univariate acidity, simulated 2D datasets and real 2D medical images are used to test and experiment results suggest that our method without any priori is more suited for large sample applications than other typical methods.

Rough-set based multimodal histogram thresholding technique is effective for medical image segmentation. However, it is difficult to obtain the significant peaks and valleys of the roughness measure. Moreover, it is sensitive to the noise for medical image. In this paper, we proposed a new medical image segmentation method using rough set theory and local polynomial regression model to address those disadvantages. Firstly, compute histogram of image intensity information and histon of image intensity and spatial information. Secondly, use the local polynomial regression model to smooth the histogram and histon. The smoothed histogram correlates with lower approximation and the smoothed histon correlates with upper approximation. Lastly, rough measure is calculated with the lower and upper approximations. And then, multimodal thresholding method is applied to medical image segmentation. The local polynomial regression model can obtain a smooth rough measure and has two advantages: first, it is easy to find the real peaks and valleys of the smoothed roughness measure to segment medical image; second, the local polynomial regression reduces the effect of noise and can find the thresholds correctly. The proposed approach is compared with the histogram based approach, histon based approach, and rough set with the histogram and histon based approach. Experimental results demonstrate that our approach can find the real peaks and valleys more easily and yields better segmentation results than those of other three methods.

Objective: To evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) and to investigate the association of the status of KRAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome. Methods: Twenty-eight patients with advanced NSCLC were enrolled in this single center, uncontrolled pilot clinical study. All the patients developed drug resistance or disease progression after first-line chemotherapy of either a docetaxel + cisplatin regimen or a vinorelbine + cisplatin regimen and then received nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy. Eight cases were stage IIIB and 20 were stage IV. An i.v. dosage regimen of 200 mg of nimotuzumab was given as a single dose, injected into the patient at days 1, 8 and 15; i.v. gemcitabine was injected at a dose of 1000 mg/m2 at days 1 and 8 and cisplatin (25 mg/m2 i.v.) at days 1, 2 and 3. Each patient received four or more therapeutic cycles. The efficacy and toxic reactions were evaluated, as well as time to progression and overall survival. Results: In total, 28 patients with advanced NSCLC received 101 therapeutic cycles. The mean cycle number was 3.6. Median time to progression was 4.9 (2.5–6.5) months; median overall survival and 1-year survival rate were 9.8 months and 48.5%, respectively. There was one case of complete response, six cases of partial response, 11 cases of stable disease and 10 cases of progressive disease. Response rate was 25%, and clinical benefit rate was 64.3%. Major toxic reactions were bone marrow suppression and gastrointestinal reaction. Only one patient developed grade I acneiform eruption. Conclusion: Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced NSCLC was active and well-tolerated in this setting. Patients with EGFR amplification and KRAS gene wild type had a better prognosis. Prospective, randomized, controlled, large-scale clinical studies are needed to confirm the results.

To solve the problem of over-reliance on a priori assumptions of the parametric methods for finite mixture models and the problem that monic Chebyshev orthogonal polynomials can only process the gray images, a segmentation method of mixture models of multivariate Chebyshev orthogonal polynomials for color image was proposed in this paper. First, the multivariate Chebyshev orthogonal polynomials are derived by the Fourier analysis and tensor product theory, and the nonparametric mixture models of multivariate orthogonal polynomials are proposed. And the mean integrated squared error is used to estimate the smoothing parameter for each model. Second, to resolve the problem of the estimation of the number of density mixture components, the stochastic nonparametric expectation maximum algorithm is used to estimate the orthogonal polynomial coefficient and weight of each model. This method does not require any prior assumptions on the models, and it can effectively overcome the problem of model mismatch. Experimental performance on real benchmark images shows that the proposed method performs well in a wide variety of empirical situations.

Because of too much dependence on prior assumptions, parametric estimation methods using finite mixture models are sensitive to noise in image segmentation. In this study, we developed a new medical image segmentation method based on non-parametric mixture models with spatial information. First, we designed the non-parametric image mixture models based on the cosine orthogonal sequence and defined the spatial information functions to obtain the spatial neighborhood information. Second, we calculated the orthogonal polynomial coefficients and the mixing ratio of the models using expectation-maximization (EM) algorithm, to classify the images by Bayesian Principle. This method can effectively overcome the problem of model mismatch, restrain noise, and keep the edge property well. In comparison with other methods, our method appears to have a better performance in the segmentation of simulated brain images and computed tomography (CT) images.

The Gaussian mixture models (GMMs) is a flexible and powerful density clustering tool. However, the application of it to medical image segmentation faces some difficulties. First, estimation of the number of components is still an open question. Second, the speed of it for large medical image is slow. Moreover, GMMs has the problem of noise sensitivity. In this paper, the kernel density estimation method is used to estimate the number of components K, and three strategies are proposed to improve the segmentation speed of GMMs. First, a histogram stratification sampling strategy is proposed to reduce the size of the training data. Second, a binning strategy is proposed to search the neighbor points of each center data to compute the approximate density function of the samples. Third, a hill-climbing algorithm with the dynamic step size is designed to find the local maxima of the density function. The kernel density estimation method and sampling technology reduce the effect of noise. Experimental results with the simulated brain images and real CT images show that the proposed algorithm has better performance in generating explainable segmentations with faster speed than the common GMMs algorithm.

A genetic linkage map of Brassica rapa ssp. pekinensis was constructed with 186 AFLP (amplified fragment length polymorphism) markers by using a doubled-haploid (DH) population with 183 individuals. The individuals were derived from F 1 which was developed by crossing a bolting resistant DH line Y-177-12 and an easy bolting DH line Y195–93a. AFLPs were generated by the use of restriction enzymes EcoR I and Mse I. The segregation of each marker and linkage was analyzed by using JoinMap version 3.0. Mapped markers were aligned in ten linkage groups which covered 887.8 cM with an average marker interval of 4.47 cM. Markers showing skewed segregation ratio were clustered in six LGs. Quantitative trait loci (QTL) were mapped for bolting resistance by using MAPQTL 4.0 package. Four QTLs explaining from 7.0 to 9.4% of the total variation were detected, all of them increase bolting resistance. These mapped QTLs could be used to develop a marker assisted selection programme for bolting resistance breeding.

The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis.Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value0.05 was considered to be significant.The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P0.001), clinical stage (P0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR =2.244, P=0.028).The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC.

In the present work we undertook the complete mitochondrial genome sequencing of an important cholangiocarcinoma model inbred rat strain for the first time. Its mitogenome was 16,312 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. A total of 96 SNPs were examined when compared to reference BN sequence.

This paper focuses on the research on how to determine the attribute layout in integrated query interfaces. Our algorithm is low in time complexity and easily expandable. In this paper, the structure of query interfaces are modelled into a tree before an integrated query interface tree is built by mining frequent pattern sub-tree so that it can satisfy structural constraints and sequence constraints between attributes to the maximum. Experiment results which integrate query interfaces of eight domains have proved that the algorithm proposed in this paper is effective.

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation-inducible sequence CC(A/T)(6) GG (known as CArG elements).Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo.The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer-specific characteristics. The chimeric promoter was better at driving radiation-inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter-mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice.The current results indicated that a combinational cancer-specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment.

There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.MBC patients aged65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy.The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%).Capecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.

Gaussian Mixture Models (GMMs) have interesting properties that make them useful for many different image applications because they have powerful probabilistic statistical theory basis. However, the application of GMMs to medical image segmentation faces some difficulties. First, many typical model selection criterions become invalid when they estimate the number of components of medical images. Second, the convergence function of GMMs suffers slow convergence. In this paper, a novel medical image segmentation method based on characteristic function of GMMs is proposed. First, a new model selection criterion using characteristic function of GMMs is proposed to estimate the number of components in medical image. Second, a new convergence function using characteristic function of GMMs is proposed to estimate the parameters of GMMs. The experimental results of CT image segmentation show that our algorithm achieves better results than those from many derivatives of GMMs and needs less computation time.

To evaluate the Angelica Sinensis as a protecting agent affecting the radiation-induced pulmonary fibrosis in an animal model,The thoraces of C57BL/6 mice were exposed to either sham irradiation or single fraction of 12 Gy. Four groups were defined: that received neither irradiation nor Angelica Sinensis (N group), that received Angelica Sinensis but no irradiation (A group), that underwent irradiation without Angelica Sinensis (NX group) and that received both Angelica Sinensis and irradiation (AX group). Mice were sacrificed at 1, 24, 72 hours and 1, 2, 4, 8, 16, 24 weeks post-irradiation. The lungs tissue were removed and processed for definitive analysis, including hydroxyproline content, HE and Masson staining, and the TGF-beta1, (Transforming Growth Factor beta1, TGF-beta1) mRNA expressions.Compared with N and A group, there was some differences in the AX group, but a significant histological and pathologic changes in NX group. Non-irradiated groups (N and A group) exhibited low levels of hydroxyproline (0.775 +/- 0.024) microg/mg and (0.751 +/- 0.034) microg/mg, and there was a significantly elevated level of hydroxyproline in NX group (0.875 +/- 0.009) microg/mg (P0.05). AX group (0.782 +/- 0.010) microg/mg was in between the non-irradiated groups (N and A group) and the radiation-only group (NX group), and the difference between AX group and NX group was significant (P0.01). The results of real-time quantitative RT-PCR showed that the relative mRNA expressions of cytokine TGF-beta1 in NX group(249.655 +/- 16.320) was significantly higher than that in group A (1.254 +/- 0.061) and N (1.324 +/- 0.057) (P0.01), and that in AX group (108.076 +/- 9.870) decreased than that of NX group (P0.01).An animal model of mice with radiation-induced lung injure was established successfully. This study has demonstrated that Angelica sinensis in Hibits the progress of radiation-induced pulmonary fibrosis, Possibly by down-regulating the expression of the proinflammatory cytokine Tgfb1. These data suggest that Angelica sinensis maybe useful in preventing and/or treating radiation-induced pulmonary fibrosis in the clinic.

To construct an eukaryotic expression vector of human telomerase reverse transcriptase (hTERT) gene specific shRNA, and investigate the effect of pshRNA-hTERT combined with gamma-irradiation on cell survival and telomerase activity.According to the coding sequence of hTERT mRNA, the target of RNAi was designed, and recombinant expression plasmid pshRNA-hTERT was constructed. The vector was transfected into Hep-2 cells. The radiosensitivity of Hep-2 cells was determined by clonogenic assay. Telomeric repeat amplification protocol (TRAP-PCR-ELISA) was used to observe the telomerase activity in each group. Results Recombinant expression vector pshRNA-hTERT was successfully transfected into Hep-2 cells. The hTERT expression inhibition rate reached 60. 8%. pshRNA-hTERT not only inhibited telomerase activity of Hep-2, but also inhibited the raise of telomerase activity induced by gamma-irradiation. Exposure of Hep-2 cells to pshRNA-hTERT for 24 hrs before irradiation resulted in a decrease in mean surviving fraction of Hep-2 cells compared with cells of group with irradiation alone (67. 7% vs 85. 7%, P0. 05) .RNAi showed a significant inhibitory effect to the expression of hTERT. The results indicate that pshRNA-hTERT can effectively inhibit telomerase activity of Hep-2 cells treated or untreated with 2 Gy gamma-irradiation and significantly enhance the radiosensitivity of Hep-2 cells in vitro. The role of radiosensitization of pshRNA-hTERT may be related with the inhibition of telomerase activity.

Texture and color are important features in analyzing images of natural scenes. Fractal descriptors based on quaternion Fourier transform and local polynomial regression are proposed for color texture image analysis. First, considering the relation between the power spectrum and frequency in the quaternion Fourier transform domain, we proposed fractal dimensions of a color image using a fast quaternion Fourier transform. Second, local polynomial regression is applied to estimate log(spectrum)–log(frequency) curve, which is not usually linear in a natural texture image. Finally, a local polynomial regression curve is defined as fractal descriptors for the color image classification problem with multiclasses. The experimental results show that our proposed approach is more effective than other color texture analysis methods both in the correct classification rate and the duration.

Radiotherapy of thoracic cancer often causes pulmonary inflammation leading to pneumonitis and fibrosis. We favor the hypothesis that cytokine-mediated multicellular interactions may result in the overexpression of proinflammatory cytokines such as TNF-alpha and TGF-beta1, which promotes progressive radiation-induced lung injury. The root of Angelica sinensis, known as 'Danggui' in Chinese medicine, is widely used to treat radiation-induced pneumonitis in humans and shows clinical efficacy and low/no toxicity with an unclear mechanism. Using quantitative RT-PCR and immunohistochemistry (IHC) methods, we investigated radiation-induced lung injury in a mouse model. C57BL/6 mice were assigned to 4 groups: no treatment (NT), Angelica Sinensis treatment only (AS), X-ray irradiation only (XRT, single fraction of 12 Gy irradiation to the thoraces) and AS treatment plus XRT (AS/XRT). Mice in NT and AS groups exhibited low TNF-alpha and TGF-beta1 mRNA levels and few positive cell counts for TNF-alpha (8-17 cells per field, x400 magnification) and TGF-beta1 (9-31 cells per field), respectively. In XRT mice, there were increased inflammatory cells positive for TNF-alpha and TGF-beta1 in lung tissue compared with NT mice (P0.01). However, when XRT mice received AS treatment (AS/XRT), the number of inflammatory cells in lung tissue positive for both TNF-alpha and TGF-beta1 was decreased compared with XRT-only mice (P0.01) accompanied by moderately decreased mRNA levels of TNF-alpha and TGF-beta1. We conclude that radiation induces expression of TNF-alpha and TGF-beta1 in the inflammatory cells of irradiated lung tissue during the pneumonic phase. The predominant localization of TNF-alpha and TGF-beta1 in inflammatory cell infiltrates suggests these cytokines' involvement in the process of radiation-induced pneumonitis. Moreover, effective down-regulation of TNF-alpha and TGF-beta1 in irradiated lung tissue by Angelica Sinensis is, at least in part, indicative of its clinical efficacy in treating radiation-induced pneumonitis.

To investigate the relationship between the signal transducer and activator of transcription 6 (STAT6) and human colon cancer.Four STAT6-specific recombinant plasmid vectors, pshRNA-STAT6-1, 2, 3, and 4 were constructed and transfected into the cultured human colon cancer cells of the line HT-29. Seventy-two hours later RT-PCR was used to detect the mRNA expression of STAT6 and the apoptosis-related genes Bcl-2 and Bax, flow cytometry (FCM) was used to detect the protein expression of phopho-STAT6 (pSTAT6). HT-29 cells were inoculated into a plate and transfected with pshRNA-STAT6-1 or pshRNA-STAT6-4, and HT-29 cells without transfection were used as controls. Seventy-two hours later FCM was used to observe the cell apoptosis. Another HT-29 cells were inoculated into a plate and transfected with pshRNA-STAT6-1 or pshRNA-STAT6-4, or blank liposome as controls. Seventy-two hours later. Western blotting was used to detect the protein expression of Bcl-2 and Bax genes.The p-STAT6 protein expression rate was 3.2% +/- 0.6% in the pshRNA-STAT6-1 group, significantly lower than that of the blank control group (18.2% +/- 0.9%, P0.01) with an inhibition rate of 82.4%, and was 7.9% +/- 0.4% in the pshRNA-STAT6-4 group, significantly lower than that in the blank control group too (P0.01) with an inhibition rate of 56.6%. And the p-STAT6 protein expression rates of the pshRNA-STAT6-2 and pshRNA-STAT6-3 groups were 16.6% +/- 0.5% and 17.1% +/- 0.7% respectively, both not significant different from that of the blank control group (both P0.05). The early cell apoptosis rates of the pshRNA-STAT6-1 and pshRNA-STAT6-4 groups were 13.0% and 8.8% respectively, both significantly higher than that of the blank control group (0.4%, both P0.05). The mRNA expression of Bcl-2 was significantly lower and the mRNA expression of Bax was significantly higher in the pshRNA-STAT6-1 and pshRNA-STAT6-4 groups than in the blank control and blank liposome groups (all P0.01). The protein expression patterns of Bcl-2 and Bax was consistent with that of their protein expression.STAT6 signaling pathway inhibits the apoptosis of colon cancer cells by regulation of the Bcl-2 and Bax genes.

Transcription factor Snail mediates epithelial-mesenchymal transition (EMT), and is associated with tumor metastasis. This study was designed to observe the enhancive effect of Snail and the reverse effect of antisense-Snail on EMT of tumor cells, and explore the role of Snail in tumor metastasis.Snail cDNA was transfected into canine renal epithelial cell line MDCK; antisense-Snail was transfected into human breast cancer cell line MDA-MB231. The expression of epithelial markers E-cadherin, beta-catenin and Cytokeratin 18, mesenchymal marker Fibronectin, metastasis-related marker matrix metalloproteinase-2 (MMP-2), and RhoA were detected by Western blot. The metastatic potential of tumor cells was examined by in vitro cell wound model and Boyden chamber invasion assay.The invasion potential of MDCK cells was enhanced after transfection of Snail. The expression of E-cadherin, beta-catenin, and Cytokeratin 18 was significantly lower in Snail-transfected MDCK cells than in control cells (P0.05); the expression of Fibronectin, MMP-2, and RhoA was significantly higher in Snail-transfected cells than in control cells (P0.05). Inhibiting the expression of Snail with antisense-Snail in MDA-MB231 cells led to opposite results.Snail promotes EMT in normal epithelial cells, and inhibiting the expression of Snail may reverse EMT and suppress tumor metastasis.

Many studies showed that telomere length and telomerase activity closely correlate with proliferation and malignant degree of tumor cells, and both of them might be involved in the repair of radiation-induced DNA damage. So it was speculated that telomere length and telomerase activity maybe correlate to radiosensitivity of carcinoma cells. This study was designed to investigate the correlations of telomere length and telomerase activity to radiosensitivity of human laryngeal squamous carcinoma cell line Hep-2.Hep-2 cells were irradiated with 0, 2, 4, 8, or 12 Gy of gamma-ray for 3 times. Survival cells were subcultured for 20 generations. Radiosensitivity index, survival fraction at 2 Gy (SF(2)), was measured by clone formation assay. Telomere length (mean length of telomere restriction fragments, TRF) was examined by Southern blotû telomerase activity (TA) was detected by polymerase chain reaction-based telomeric repeat amplification protocol (PCR-TRAP) coupled with ELISA.After different doses of irradiation, SF(2) of Hep-2 cells was 0.47-0.64; TRF was 3.76-9.43 kb; TA was 1.761-2.606. Each parameter had significant differences among the survival progenies (P0.05). SF(2) was positively correlated with TRF (r=0.921, P0.01), and negatively correlated with TA (r=-0.929, P0.01); TRF was negatively correlated with TA (r=-0.944, P0.01).Radiosensitivity of Hep-2 cells negatively correlates with telomere length, and positively correlates with telomerase activity, which suggest that both telomere length and telomerase activity may be used to predict cellular radiosensitivity.

Fusion of the egg and the sperm cells in plants produces a zygote that develops into an embryo. Screening of ethyl methanesulfonate-mutagenized populations of Arabidopsis led to the identification of EMBRYONIC FACTOR 1 (FAC1), a locus that gives a zygote-lethal phenotype when mutated. The FAC1 gene was identified by positional cloning and confirmed by a genetic complementation test against a T-DNA insertion allele. It encodes an AMP deaminase (AMPD) that is known in human and yeast to convert AMP to IMP to maintain the energy potential. Expression of FAC1 in a yeast AMPD mutant after removal of its N-terminal putative transmembrane domain complemented the mutant phenotype, suggesting a functional conservancy but a structural divergence through evolution. Although a low level of FAC1 expression was observed in all organs tested, using a reporter construct we observed a significantly increased FAC1 expression in the zygote, early embryo and endosperm. Furthermore, during somatic embryogenesis, a high level of FAC1 expression was observed in developing embryos including putative embryogenic cells. FAC1, therefore, represents one of the earliest expressed genes known in plants. It may act through AMP depletion to provide sufficient energy for the zygote to proceed through development.

A full length cDNA clone encoding invertase inhibitor was isolated by RT-PCR combined with 5' RACE from potato (S. tuberosum) tubers of cv. JH and designated as St-inh. The encoding region of St-inh is of 663bp encoding a protein of 221 amino acids. The DNA fragment including St-inh cDNA was cloned into the vector pET28a (+) and expressed successfully in E. coli. Co-incubation of the proteins produced by St-inh in E. coli and the invertase extracts from potato tubers of cv. E1, JH and tomato fruits showed that the invertase activities of potato tubers and tomato fruits decreased by 34.3%, 21% and 33.8% respectively. These results indicated that products of St-INH protein had a function of invertase inhibitors. The analysises of the nucleotide and amino acid sequences using BLAST and T-COFFEE demonstrated that St-inh cDNA was of over 95% homologous to Kunitz-type C and there was a typical domain of Kunitz-type protein [L, I, V, M]-X-D-X-[E, D, N, T, Y-[D, G]-[R, K, H, D, E, N, Q]-X-[L, I, V, M]-X(5)-Y-X-[L, I, V, M. Therefore, it was conjectured that St-inh could be a member of Kunitz-type gene family.

Suppression subtractive hybridization (SSH) was applied in the search of the genes induced during the interaction between Phytophthora infestans and horizontal resistance potato (R-gene-free). A subtractive library of potato, which highly enriches for resistance-related genes to P. infestans, was constructed. The potato leaves after inoculating 48 h with mixture of P. infestans races were used as "tester" and uninoculated leaves as "control" in the experiments. Total 150 of 840 randomly chosen cDNA clones were identified with the reveres Northern dot-blot screening method. The sequencing results of 26 clones indicated that several fragments were previously shown to be activated during resistance responses. Seven differentially expressed fragments had significant homologous with EST of potato leaves inoculated with P. infestans. The sequences of nucleotide or amino acids of partial cDNA fragments shared identity with tomato, tobacco and Arabidopsis while four cDNA fragments that had no significant homology with EST in GenBank were expected to be new genes involved in the disease response.