Cancer metastasis is composed of a complex cascade that involves a variety of critical steps beginning with detachment from the primary tumor and ending with growth of tumor at a distant site, such as bone. The "seed-and-soil hypothesis" predicts that the bone microenvironment expresses factors through which attract a variety of cancer cells and promote the tumor development. The ending point of tumor development in bone is achieved through the bidirectional and dynamic interaction between tumor cells and the cells in their growth microenvironment. A variety of factors produced by the bone microenvironment, contribute to the pathogenesis of cancer skeletal metastasis. In this review, using prostate cancer (CaP) as an example, some of general mechanisms of cancer metastasis will be summarized. In addition, the current understanding of the interaction between tumor cells and the bone microenvironment will be addressed. Finally, the research directions in the near future will be suggested.

Glioma is the most common form of brain cancer. Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to its infiltrative nature. It has important significance to improve the treatment of glioma through in-depth understanding the intracerebral metabolic characteristics and pharmacokinetics of chemotherapeutics. Brain microdialysis (B-MD), an effective method to monitor central nervous system anticancer drug disposition, conditions of drugs through the blood-brain barrier, basic pathophysiologic metabolism, bioactive compounds and the changes of neurotransmitter in brain, provides the unique opportunity to allow the simultaneous determination of unbound concentrations of drugs in several tissues, and directly measure gliomas biochemistry continuously. B-MD has been able to monitor the change of brain drugs, metabolites and neurotransmitters, dynamic analysis of the drug concentration and pharmacological effect after administration, pharmacodynamic interaction between drugs, receptor mechanism of drug transport, as well as feedback information of internal environment. B-MD is expected to provide reference for clinical individual chemotherapy of glioma, but also provide powerful tools for the evaluation of new anticancer drugs in vivo. In this review, a comprehensive overview of B-MD for studies on glioma is elucidated with special emphasis on its application to neurochemistry and pharmacokinetic studies.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Blood-Brain Barrier ; Brain Neoplasms ; metabolism ; Glioma ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Metabolomics ; methods ; Microdialysis ; methods ; Neurotransmitter Agents ; pharmacokinetics ; Pharmaceutical Preparations ; metabolism ; Positron-Emission Tomography

Objective:To screen out the potential key genes of endotoxin tolerance (ET), and to provide theoretical and experimental evidence for treatment and prognosis of sepsis.Methods:①Experiment 1 (gene chip and bioinformatics analysis): ET related data set GSE47783 was downloaded from the Gene Expression Omnibus (GEO). The data set was obtained from lipopolysaccharide (LPS) stimulated mouse macrophages to establish sepsis model (LPS group) and ET model (ET group). IDEP 0.92 software was used to screen differential expressed gene (DEG) between the two groups, analyze gene ontology (GO), and locate the main functions and signaling pathways of differential genes. The protein-protein interaction (PPI) network of DEG was constructed by the Search Tool for the Retrieval of Interacting Genes Database (STRING) to screen core genes hepatitis A virus cell membrane protein receptor 2 (HAVCR2) for following up validation study. ②Experiment 2 (reproduction of mouse macrophage RAW264.7 model): RAW264.7 cells were cultured in vitro, the ET model (ET group, cells were cultured with 10 μg/L LPS for 24 hours and then with 100 μg/L LPS for 4 hours) and sepsis model (LPS group, cells were cultured with 100 μg/L LPS for 4 hours) were reproduced by LPS stimulation. Phosphate buffer saline (PBS) group was given equal volume of solvent PBS for 4 hours. The mRNA and protein expressions of HAVCR2 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. ③Experiment 3 (RAW264.7 cells transfected with HAVCR2 lentiviral vector): to further clarify whether HAVCR2 was involved in the formation of ET, after knockdown of HAVCR2 in RAW264.7 cells by lentiviral short hairpin RNA (shRNA) technology, the ET model (HAVCR2 --ET group) was constructed again, and the control group (ET group) without knockdown of HAVCR2 was set up. RT-qPCR method was used to detect the mRNA expressions of macrophage polarization key proteins [arginase 1 (ARG1), CD206, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nitric oxide synthase 2 (NOS2)] in cells. Results:①Experiment 1: a total of 1 013 DEG were identified, compared with LPS group, 521 genes were up-regulated and 492 genes were down-regulated in ET group. The function of these DEG was to increase biosynthesis and reduce inflammatory reaction. Signal pathways were mainly enriched in Janus kinase/signal transducers and activators of transcription (JAK/STAT) , NOD like receptor, Toll-like receptor (TLR), TNF, hypoxia inducible factor-1 (HIF-1). The first up-regulated HAVCR2 in the ET group was selected as the target of the study. ②Experiment 2: the results of in vitro experiment showed that the mRNA expression of HAVCR2 after high-dose LPS stimulation was down-regulated as compared with PBS group, and the mRNA expression of HAVCR2 in ET group was significantly higher than that in LPS group (2 -ΔΔCT: 1.10±0.10 vs. 0.60±0.10, P < 0.05). The results of Western blotting were consistent with RT-qPCR results. ③Experiment 3: the mRNA expressions of ARG1 and CD206 in HAVCR2 --ET group were significantly lower than those in ET group [ARG1 mRNA (2 -ΔΔCT): 0.50±0.10 vs. 1.00±0.10, CD206 (2 -ΔΔCT): 0.73±0.10 vs. 1.00±0.10], and the mRNA expressions of TNF-α and IL-1β were significantly higher than those in ET group [TNF-α mRNA (2 -ΔΔCT): 2.20±0.10 vs. 1.00±0.10, IL-1β mRNA (2 -ΔΔCT): 9.00±0.10 vs. 1.00±0.10), with significant differences (all P < 0.05). There was no significant difference in the expression of NOS2 mRNA between the two groups. Conclusion:HAVCR2 is involved in the regulation of inflammatory factors downstream of sepsis and the formation of ET, which is expected to become a new therapeutic target of sepsis.

KRAS mutation is one of the most frequent driver gene mutations found in patients with non-small cell lung cancer (NSCLC). KRAS-mutant NSCLC is highly heterogeneous. Various mutation types and different co-mutational signatures affect tumor biological behavior and therapeutic responses. NSCLC patients with KRAS mutations could relatively benefit from immunotherapy, while the effects of KRAS mutations on chemotherapy are still controversial. The treatment methods of KRAS-mutant lung cancer have followed the therapy of NSCLC without driver gene mutation for a long time. With the introduction of novel KRAS G12C inhibitors in the clinic, the therapeutic landscape has begun to change and has made the preliminary advance, and the combined therapies resulted in encouraging signals of efficacy both in preclinical and early phase trials. This paper reviews the biological and clinical characteristics as well as the latest treatment progress of KRAS-mutant NSCLC.

A novel biosensor for aflatoxin B1 detecting has been reported. The biosensor electrode for AFB1 detecting was assembled by immobilized aflatoxin-oxidoreductase using open-ended multi-walled carbon nanotubes as matrix. Its linear range was between 0.16?M and 3.2?M. And if the specific anti-aflatoxin B1 antibody and aflatoxin oxidoreductase were both immobilized on the electrode with Multi-Walled carbon nanotubes, the detection limit of the modified electrode could be 16 nM with a 10 times improved sensitivity. The aflatoxin enzyme biosensor assembled this way strode one step forward its practical application.

Objective To establish a rapid method having great capability for enrichment and anti-interference, higher sensitivity and good precision for determination of trace silver in drinking water. Methods The conditions of determination such as the definition of peak potentials, the selection of auxiliary electrolytes, the selection of kind and amount of oxidants and anti-interference test were carried out by MP-1 potentiometer using glass-carbon electrode. Results The lowest detection limit, average recorery rate and average relative standard deviation were 0.004 ug/ml, 100.3% and 2.73% respectively. Conclusion This method was suitable for determination of trace silver in drinking water.

Objective To evaluate the surgical technique of titanium miniplates in reconstruction of laminar roof after a posterior approach in intraspinal tumor surgery. Methods From August, 2007 to March, 2009, 11patients underwent intraspinal tumor surgery with osteotomy and reconstruction of laminar roof, titanium miniplates were used for fixing in the re-implantation. There were 2 intramedullary tumors,9 extramedullary tumors. The target of surgery was the cervical spine in 2 cases, the cervicothoracic spine in 4 cases, the thoracic spine in 2 cases, the thoracolumbar spine in 2 cases, and the lumbar spine in 1 cases. The patitens were followed up for 6 months to 2years. Local pain,bony healing and spinal malformation were assessed. Results In the 11 patients, there was no case of dural, nerve root, or spinal cord injury due to laminar roof reconstruction. One patient complained of moderate to severe local pain during follow-up and 2 patients complained of occasional slight pain at the surgical site. No limitation of activity occurred. Bony healing was confirmed radiologically or CT scan in 9 patients. There were no patients demonstrated a new spinal malalignment, and no patients developed stenosis of the spinal canal. Conclusions The reconstruction of the laminar roof using titanium miniplates will benefit the recovery of normal structure of spine,and maintain the stability of spine,and avoid the occurrence of stenosis of the spinal canal.

Objective To evaluate the efficacy and adverse effects of gefitinib as the first line treatment in elderly patients with lung adenocarcinoma.Methods 81 elderly patients of previously untreated advanced lung adenocarcinoma,who were non-smokers and unsuitable for chemotherapy,received gefitinib treatment until disease progression or intolerable toxicities occurred.The curative effect performance status of improvement and adverse effects were observed.Results All of the patients were evaluable.Partial response rate and stable disease rate of gefifinib were 25.9 ％ (21/81) and 48.1％ (39/81),respectively.55.5 ％ (45/81)of patients had performance status improved after treatment.Conclusion Gefitinib has curative effect and is well tolerated in the treatment of elderly patients with previously untreated advanced lung adenocarcinoma.

Objective To explore the association of dietary behavior of children with Tourette syndrome (TS) and tic symptoms.Methods 207 TS children and their 264 corresponding controls,who visited our hospital during the period of November 2008 to October 2010,were investigated with children' s dietary behavior questionnaire,under the guidance of professional staff,and the TS tic symptom severity was also evaluated according to The Yale Global Tic Severity Scale (YGTSS).Kruskal-Wallis H rank-sum test was applied for univariate analysis and multinominal logistic regression for further multivariate analysis,with values of odds ratio (OR) and population attributable risk (PAR) obtained to demonstrate the relation strength between dietary behavior and tic symptom severity.Results Results of univariate analysis showed that western fast meal,barbecues,cream food,cold food,and spicy food were related to TS tic symptom severity (P＜0.05).Results of multivariate analysis demonstrated that western fast meal,fruits and vegetables,cream food and spicy food were risk factors for mild TS compared with control group,with OR and 95％ CI of 3.282 (1.922,5.064),2.239 (1.298,3.861),2.341 (1.355,4.046),2.118 (1.327,3.380) and their corresponding PAR of 0.306,0.464,0.169,0.250 respectively.As to moderate and severe TS,the risk factors included western fast meal,fruits and vegetables,and spicy food,with their respective OR and 95％ CI of 2.581 (1.322,5.038),2.364 (1.166,4.795),1.822 (1.014,2.272) and PAR of 0.234,0.487,0.197.Conclusion Dietary behavior,especially western fast meal,fruits and vegetables,cream food and spicy food,are considered to be associated with TS tic symptom severity.Therefore it' s obligatory to rectify undesirable dietary behaviors for TS children.

BACKGROUND:Injection of isoproterenol is known to induce proliferation and hypertrophy of acinar cells in rodent salivary glands. However, the clonal proliferation ability of stem/progenitor cells of salivary glands by isoproterenol remains unclear.
OBJECTIVE:To study the proliferation and activation ability of stem/progenitor cells of submandibular gland with colony assay by intraperitoneal injection of isoproterenol.
METHODS:Sprague-Dawley rats were randomly divided into two groups, isoproterenol and control groups, respectively intraperitonal y injected with isoproterenol and normal saline for 5 consecutive days. The gland tissues were harvested, and the stem/progenitor cells of submandibular gland were obtained by enzyme digestion in vitro. The number of clonal colonies of each group was analyzed. The larger colony cells were col ected for immunohistochemistry staining with CD90.1, laminin andα6β1.
RESULTS AND CONCLUSION:The number of middle and low proliferative potential colony-forming cells was less but high proliferative potential colony forming cells were significantly more in isoproterenol group compared with control group (P<0.05). However, there was no significant difference in the total number of the colonies between two groups (P>0.05). The high proliferative potential colony forming cells were positive for CD90.1, laminin andα6β1. Results showed that isoproterenol treatment model cannot increase the cellnumber, but enhance the proliferation ability of stem/progenitor cells from the submandibular gland.