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

Background Long-term administration of glucocorticoid drugs induces ocular hypertension in susceptible individuals probably.It has been verified that 1 1β-hydroxysteroid dehydrogenase type 1 (11β-HSD1),glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) can affect the generating of aqueous humor,but how they play the role in glucocorticoid-induced ocular hypertension is unclear.Objective This study was to investigate the relationship of expressions of 11β-HSD1 and steroids receptors in ciliary body and steroid-induced ocular hypertension.Methods Thirteen 12-16 week-old New Zealand albino rabbits were randomized to control group (5 rabbits) and experimental group (8 rabbits).Steroid-induced glaucoma models were induced by administration of subconjunctival injection of 5 mg dexamethasone solution(1 ml) and 0.5％ dexamethasone eye drops on alternate days in the left eyes for consecutive two months in the experimental group,and the equal volume of sterile normal saline solution was used in the same way in the control group.The successful criteria of model eyes was defined as rising of intraocular pressure (IOP) to ≥ 18 mmHg for over one week.Then,the animals were sacrificed by excessive anesthesia and the ciliary tissues were isolated for the assay of expressions of 1 1β-HSD1 protein by immunochemistry,and the expressions of 11β-HSD1 mRNA,GR mRNA and MR mRNA in ciliary body were semi-quantitatively detected by reverse transcription-PCR (RT-PCR).The experimental results were compared between the two groups.Results The IOP was normal in the first two weeks after administration of drugs,and no significant difference was found in IOP between the first week and the second week in the experimental group (q =0.469,P ＞0.05).From 3 through 5 weeks after injection,the IOP was gradually elevated,with the highest value of (18.87±0.77) mmHg in the fifth week.Significant differences were seen between the two groups at mentioned-above time points (q =10.535,20.353,28.681,all at P ＜ 0.01).11β-HSD1 protein was positively expressed in nonpigmented epithelial cells of ciliary tissue of rabbits in both groups,however,the expression intensity was weaker in the experimental group compared with the control group.The relative expressional values of MR mRNA,GR mRNA and 11β-HSD1 mRNA in the ciliary tissue were 2.22±0.78,0.64±0.11 and 0.47±0.16 in the experimental group,and those in the control group were 0.94±0.27,1.88±0.74 and 2.68±1.28,with significant differences between the two groups (t =6.070,P =0.004 ; t =5.170,P =0.007 ; t =5.540,P =0.005).Conclusions Corticosteroidinduced glaucoma probably is associated with the up-regulation of MR level and down-regulations of GR and 11β-HSD1 in ciliary body.

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.

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.

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 0.16μM and 3.2μM. 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 investigate the effects of Working Memory Training System on working memory impairment after brain injury. Methods From November, 2013 to March, 2015, 20 patients of brain injury with impairment of working memory were divided into training group (n=10) and control group (n=10). The training group was trained with the Working Memory Training System for four weeks, while the control group did not accept any cognitive rehabilitation. They were tested with digital forwards/backwards, space forwards/backwards, n-back test and Everyday Memory Questionnaire before and after training. Results All of the tests improved more in the training group than in the control group (Z>2.014, P<0.05), except that of digital forwards, as well as the score of Everyday Memory Questionnaire (Z=1.970, P=0.049). Conclusion Application of Working Memory Training System can improve the ability of memory in patients with brain injury, both the working memory and everyday memory.

Objective To study the effects of prokaryotic ubiquitin-like protein ( Pup)-proteasome system on the growth of Mycobacterium strains.Methods The genes encoding Pup ( pup gene) and protea-someβsubunit ( prcB gene) were respectively knocked out from Mycobacterium smegmatis ( M.sm) strains by homologous recombination.The growth and viability of the wild-type and mutant strains of M.sm were an-alyzed under normal culture condition and under hypoxia as well as anaerobic conditions.Results The pup and prcB genes were completely and precisely knocked out from M.sm strains and the mutant strains were named △SM-Pup and△SM-prcB, respectively.The△SM-Pup strains grew faster than the wild type ( WT) and△SM-prcB strains.No significantly differences in the growth of M.sm were found between the WT and△SM-prcB strains.Conclusion The Pup-proteasome system was involved in the growth of M.sm, espe-cially the pup gene.There was difference between pup and prcB genes in regulating the growth of M.sm.The functions and influences of Pup-proteasome system still need further investigation.

Objective To evaluate the effect of nutrition support on nutritional status and clinical outcome of patients at nutritional risk in internal medical departments.Methods 148 patients at nutritional risk as identified by Nutritional Risk Screening 2002 were numbered according to the order of admission and divided into standard care group (control group,odd numbers,n =75) and individualised nutrition support group (intervention group,even numbers,n =73).Intervention consisted of encouraging food intake,designing food plan,and assuring implementation of food prescription.Energy and protein intake,body weight,length of hospital stay,hospitalization expenses and complications were compared between the two groups.Results In the interventions group,protein intake was significantly higher than that in the control group [(45.1 ± 2.2) g/d vs.(54.8±2.5) g/d,P=0.004],and energyintake higher than that in the control group [(4 180.0± 227.4) kJ/d vs.(4 589.6 ± 150.5) kJ/d,P =0.135] but without statistical significance.Intervention led to an intake of ≥75％ of requirements in 46.6％ patients in the intervention group,significantly higher than the proportion in the control group (30.7％) (P =0.047).The change of body weight was significantly smaller in the intervention group than in the control group [(-0.4 ± 0.2) kg vs.(-1.1 ± 0.2) kg,P =0.025].The length of hospital stay,hospitalization expenses,and incidence of complications showed no significant differences between the control group and the intervention group [(13.5 ±0.9) d vs.(12.4 ±0.6) d,P=0.310;(17834±1824) yuanvs.(16099±1243) yuan,P=0.435;12.8％ vs.8.1％,P=0.184].Conclusions Patients at nutritional risk in internal medical departments could benefit from nutrition support in terms of protein intake and body weight maintenance.A large-scale randomized controlled trial is necessary to confirm the effect of nutrition support on clinical outcomes of patients at nutritional risk.