Genetic Fingerprint Concerned with Lymphatic Metastasis of Human Lung Squamous Cancer

Background and objective With the most recent introduction of microarray technology to biology, it becomes possible to perform comprehensive analysis of gene expression in cancer cell. In this study the laser microdissection technique and cDNA microarray analysis were combined to obtain accurate molecular profiles of lymphatic metastasis in patients with lung squamous cell carcinoma. Methods Primary lung squamous cancer tissues and regional lymph nodes were obtained from 10 patients who underwent complete resection of lung cancer. According to the source of lung cancer cells, the samples were classified into three groups: the primary tumor with lymphatic metastasis (TxN+, n=5), the primary tumor without lymphatic metastasis (TxN-, n=5) and matched tumor cells from metastatic lymph nodes (N+, n=5). Total RNA was extracted from laser microdissected tumor samples. Adequate RNA starting material of mRNA from primary tumor or metastatic nodes were labeled and then hybridized into the same microarray containing 6 000 known, named human genes/ESTs. After scanning, data analysis was performed using GeneSpringTM6.2. Results A total of 37 genes were found to be able to separate TxN+ from TxN-. TxN+ have higher levels of genes concerned with structural protein, signal transducer, chaperone and enzyme. TxN- have higher levels of genes coding for cell cycle regulator, transporter, signal transducer and apoptosis regulator. Interestingly, there were no differentially expressed genes between N+ and TxN+. Conclusion The acquisition of the metastatic phenotype might occur early in the development of lung squamous cancer. We raise the hypothesis that the gene-expression signature described herein is valuable to elucidate the molecular mechanisms regarding lymphatic metastasis and to look for novel therapeutic targets

Fluctuation of circulating tumor cells in patients with lung cancer by real-time fluorescent quantitative-PCR approach before and after radiotherapy

Background and Aims: The failure to reduce the mortality of patients with solid tumours is mainly a result of the early dissemination of cancer cells to secondary site, which is usually missed by conventional diagnostic procedures used for tumour staging. The possibility to use easily accessible body fluids as a source for circulating tumour cells (CTCs) detection enables longitudinal observations of the disease. In the study, we evaluated the CTCs in lung cancer following locoregional radiation therapy. Methods: Samples of 5ml peripheral blood was taken from each lung cancer patients (n=15) both before and after the radiotherapy course. Meanwhile tumour size was determined by chest X-ray or computed tomography. Using cytokeratin 19(CK19) as marker,the blood samples were subjected to real time RT-PCR assay. All patients with lung cancer were treated with primary definitive and mediastinal radiotherapy. Results Compare to that of pre-treatment, the value of CK19 mRNA in peripheral blood after therapy decreased dramatically(5.0932\ub11.0628 vs. 4.2493\ub10.8323,t=3.192,P=0.007). The change of CK19 mRNA level before and after radiotherapy was closely related to the type (NSCLC vs. SCLC, 0.5389\ub10.9030 vs. 1.6826\ub10.9467,t=2.1465,P=0.051). Meanwhile, there appeared to be a close link between the grade (Well/Mod vs. Poor) and the change of CK19 mRNA (0.5024 vs. 1.5271,t=2.017,P=0.065). The change of CK19 mRNA level was related to variation of tumour burden during radiotherapy(r=0.0575,P=0.025). Of the 15 cases studied, 12 cases were positive before radiotherapy (12/15,80%). The positive rate was 53%(8/15) after radiotherapy, meaning that four patients converted into negative after radiotherapy. Conclusions: The disseminated circulating cancer cells can be affected by radiotherapy; meanwhile further more systemic adjuvant treatment should be conducted. Due to concordance between molecular response and radiological remission, assessment of the therapeutic response might be possible by serial quantitative of CTCs

Palaeomagnetic constraints from granodioritic plutons (Jiaodong Peninsula): New insights on Late Mesozoic continental extension in eastern Asia.

International audienceMechanism and kinematics of the Late Mesozoic continental extension event of eastern Asia are still debated. In order to better constrain its evolution, two granodioritic plutons of the Jiaodong Peninsula have been chosen as targets for a time-constrained palaeomagnetic study. Indeed, plutons are devoid of visible deformation, did not experience rotation along horizontal axis and are precisely dated by U/Pb and 40Ar/39Ar methods. Multidomain (MD) magnetite has been identified as the principal magnetic remanent carrier. The interpolation of existing and new U/Pb and 40Ar/39Ar ages revealed that characteristic remanent magnetisation was acquired in a narrow range of 116 ± 2 Ma. Twenty out of 27 sites present stable magnetic directions calculated from high-temperature or high-coercive components. The observations of the solo normal magnetic polarity for this palaeomagnetic collection and of the magnetic remanent age consistent with the Cretaceous Normal Superchron (CNS) argue that the characteristic magnetic remanence may be considered as primary. Detailed field observations of the intrusive relationship between the plutons and country rocks and Anisotropy of Magnetic Susceptibility (AMS) study reveal the absence of the subsequent deformation of plutons, or rigid rotation of plutons along a horizontal axis. Two palaeomagnetic poles have been therefore calculated from these plutons. Among 12 out 15 Cretaceous palaeomagnetic poles, including the two new poles provided by this study, from the Jiaodong Peninsula and on both sides of Tan-Lu and Muping-Jimo faults are statistically consistent. As a result, the Jiaodong Peninsula behaved as a rigid block as internal deformation appears negligible. The remaining three derived poles are probably due to the secular variation or/and the vicinity of fault zones near of the palaeomagnetic sampling site. Thus, they can not be applied to the peninsula-scaled tectonics. Comparison of these time52 constrained Cretaceous palaeomagnetic results of the Jiaodong Peninsula with those of North China Block (NCB) indicate that the Jiaodong Peninsula was rigidly attached to NCB since, 3 at least, the Cretaceous as residual difference is clearly insignificant with respect to the error brackets. These new palaeomagnetic results confirm that the relative clockwise (CW) rotation of Eastern Liaoning-Korea Block (ELKB) with respect to NCB does not affect the Jiaodong Peninsula as a rigid block, nevertheless, some tectonic structures have been reactivated since Cenozoic and local rotations could be produced. This palaeomagnetic study reveals that the Late Mesozoic extension in Eastern Asia is heterogeneously expressed in time and space. The complete understanding of the mechanism(s) of this extensional event needs further multidisciplinary investigations

CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra-or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.Peer reviewe

Proteochemometric Modeling of the Antigen-Antibody Interaction : New Fingerprints for Antigen, Antibody and Epitope-Paratope Interaction

Despite the high specificity between antigen and antibody binding, similar epitopes can be recognized or cross-neutralized by paratopes of antibody with different binding affinities. How to accurately characterize this slight variation which may or may not change the antigen-antibody binding affinity is a key issue in this area. In this report, by combining cylinder model with shell structure model, a new fingerprint was introduced to describe both the structural and physical-chemical features of the antigen and antibody protein. Furthermore, beside the description of individual protein, the specific epitope-paratope interaction fingerprint (EPIF) was developed to reflect the bond and the environment of the antigen-antibody interface. Finally, Proteochemometric Modeling of the antigen-antibody interaction was established and evaluated on 429 antigen-antibody complexes. By using only protein descriptors, our model achieved the best performance (R-2 = 0: 91; Q(test)(2) = 0: 68) among peers. Further, together with EPIF as a new cross-term, our model (R-2 = 0: 92; Q(2) test = 0: 74) can significantly outperform peers with multiplication of ligand and protein descriptors as a cross-term (R2Peer reviewe

Building osteogenic microenvironments with a double-network composite hydrogel for bone repair

The critical factor determining the in vivo effect of bone repair materials is the microenvironment, which greatly depends on their abilities to promote vascularization and bone formation. However, implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments. Herein, a double-network composite hydrogel combining vascular endothelial growth factor (VEGF)-mimetic peptide with hydroxyapatite (HA) precursor was developed to build an osteogenic microenvironment for bone repair. The hydrogel was prepared by mixing acrylated β-cyclodextrins and octacalcium phosphate (OCP), an HA precursor, with gelatin solution, followed by ultraviolet photo-crosslinking. To improve the angiogenic potential of the hydrogel, QK, a VEGF-mimicking peptide, was loaded in acrylated β-cyclodextrins. The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes, such as Flt1 , Kdr , and VEGF , in bone marrow mesenchymal stem cells. Moreover, QK could recruit bone marrow mesenchymal stem cells. Furthermore, OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration. The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity. The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats, due to perfect synergistic effects of QK and OCP on vascularized bone regeneration. In summary, improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair

TaSnRK2.9, a Sucrose Non-fermenting 1-Related Protein Kinase Gene, Positively Regulates Plant Response to Drought and Salt Stress in Transgenic Tobacco

Sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family members play crucial roles in plant abiotic stress response. However, the precise mechanism underlying the function of SnRKs has not been thoroughly elucidated in plants. In this research, a novel SnRK2 gene, TaSnRK2.9 was cloned and characterized from common wheat. The expression of TaSnRK2.9 was upregulated by polyethylene glycol (PEG), NaCl, H2O2, abscisic acid (ABA), methyl jasmonate (MeJA), and ethrel treatments. TaSnRK2.9 was mainly expressed in wheat young root, stamen, pistil, and lemma. Overexpressing TaSnRK2.9 in transgenic tobacco enhanced plants’ tolerance to drought and salt stresses both in young seedlings and mature plants with improved survival rate, seed germination rate, and root length. Physiological analyses suggest that TaSnRK2.9 improved antioxidant system such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione (GSH) to reduce the H2O2 content under drought or salt stress. Additionally, TaSnRK2.9 overexpression plants had elevated ABA content, implying that the function of TaSnRK2.9 may be ABA-dependent. Moreover, TaSnRK2.9 increased the expression of some ROS-related, ABA-related, and stress-response genes under osmotic or salt treatment. TaSnRK2.9 could interact with NtABF2 in yeast two-hybrid assay, and increased the expression of NtABF2 under mannitol or NaCl treatment in transgenic tobacco plants. In conclusion, overexpression of TaSnRK2.9 in tobacco conferred plants tolerance to drought and salt stresses through enhanced ROS scavenging ability, ABA-dependent signal transduction, and specific SnRK-ABF interaction