BACKGROUND:The tumor tissue engineering can build an integrated culture model to ful y simulate the in vivo microenvironment of tumor growth, which can be used to study tumor developmental dynamics and related treatment strategies.
OBJECTIVE:To review the three-dimensional culture of tumor cells using tumor engineering technology.
METHODS:PubMed database was retrieved for articles related to tumor engineering, three-dimensional culture of tumor cells, biological scaffold materials and tumor microenvironment published from January 1992 to March 2013.
RESULTS AND CONCLUSION:Three-dimensional culture, because of its reproducible tissue and cellgrowth in vivo, has become an important platform for study of tumor resistance, invasiveness and tumor microenvironment. The three-dimensional culture has showed a trend to gradual y replace the flat culture technique in many fields, and provides a research platform which is very close to in vivo environment. In recent years, with the development of tumor engineering, a variety of new polymer materials have been used in the three-dimensional culture of tumor cells. Three-dimensional culture technology is becoming a hotspot in the field of tumor biology, in which, using a variety of methods and materials, the cells show a growth in the spatial manner to form a biological support or matrix similar to in vivo growth environment. Biomaterials have become the soil on which seed cells can grow wel , and plays an alternative to the extracellular matrix or the matrix of tissues and organs in the tumor engineering. Therefore, the three-dimensional cellculture has been widely used in cancer research, which has become a powerful tool to tumor drug resistance, angiogenesis, cel-cellinteraction, signal transduction, stem cells and other research.

Objective To investigate the expression of FOXO3a and MMP 9 in colorectal cancer tissues and their relationship . Methods Tissue microarray and immunohistochemical SP methods were used to detect the expression of FOXO 3a and MMP 9 in 78 cases of colorectal cancer tissues and 69 cases of corresponding normal intestinal mucosa tissues ,then analyze the relation be-tween their expression and the clinicopathologic parameters of the patients ,and the relation between the expression of FOXO3a and MMP 9 .Results (1)The positive expression rate of FOXO3a in 78 cases of colorectal cancer tissues and 69 cases of normal intesti-nal mucosa tissues are 57 .69% (45/78)and 95 .65% (66/69) ,the positive expression rate of MMP 9 in 78 cases of colorectal cancer tissues and 69 cases of normal intestinal mucosa tissues are 85 .90% (67/78) and 15 .94% (11/69) ,and the difference is significant (P=0 .000) .(2)The decreased expression of FOXO3a and the increased expression of MMP 9 in colorectal cancer are significantly correlated with the depth of tumor invasion ,tumor histological differentiation ,metastasis of lymph node and TNM stage (P<0 .05) ,but there is no significant relationship with patients′age ,gender and tumor size (P>0 .05) .(3)There was a negative corre-lation between the expression of FOXO3a and MMP 9 (r=0 .272 ,P<0 .05) .Conclusion The decreased expression of FOXO3a and the increased expression of MMP 9 may be closely related with carcinogenesis ,invasion and metastasis of colorectal cancer ,and their combination may be an important indicator to evaluate the malignant degree and prognosis of the colorectal cancer .

This study aims to save cost of sampling for estimating the area under the amlodipine plasma concentration versus time curve in 24 hours (AUC(0-24 h)). Limited sampling strategy (LSS) models was developed and validated by mutiple regression model within 4 or fewer amlodipine concentration values. Absolute prediction error (APE), root of mean square error (RMSE) and visual predict check were used as criterion. The results of Jackknife validation showed that fifteen (9.4%) of the 160 LSS based on regression analysis were not within an APE of 15% by using one concentration-time point. 156 (97.5%), 159 (99.4%) and 160 (100%) of the 160 LSS model were capable of predicting within an APE 15% by using 2, 3, 4 points, separately. Limited sampling strategies have been developed and validated for estimating AUC(0-24 h) of amlodipine. The present study indicated that the implemention of both 5 mg and 10 mg dosage could enable accurate predictions of AUC(0-24 h) by the same LSS model. This study shows that 12, 4, 24, 2 h after administration are key sampling time points. The combination of (12, 4), (12, 4, 24) or (12, 4, 24, 2 h) might be chosen as sampling hours for predicting AUC(0-24 h) in practical application according to requirement.

Objective To investigate the diagnostic efficacy of fecal calprotectin(FC) on assessing endoscopic disease activity in colonic or ileo-colonic Crohn disease (CD) and CD-related surgery patients .Methods Totally 56 colonic or ileo-colonic CD pa-tients ,25 CD-related surgery patients and 25 irritable bowel syndrome (IBS) patients with previously confirmed diagnosis of CD and IBS were enrolled into this study .Fecal samples were collected from 1 to 3 day before bowel preparation and FC was measured by ELISA .Endoscopic activity was determined for colonic or ileo-colonic CD with Simple Endoscopic Score for Crohn′s Disease (SES-CD) and CD-related surgery patients with the Rutgeerts′ score .Results Among colonic or ileo-colonic CD patients ,the levels of FC in endoscopic active patients had significantly higher than that of endoscopic remission patients and IBS patients(P < 0 .01) ,there was significant correlation between levels of FC and the SES-CD (r= 0 .802 ,P< 0 .01) .FC threshold of 250 μg/g was tested to in-dicated active endoscopic disease with 97 .1% sensitivity and 71 .4% specificity .Among CD-related surgery patients ,FC level in IBS patients were significantly lower than that of endoscopic remission patients and endoscopic active patients ,but the FC in endoscopic remission patients and endoscopic active patients had no statistic difference(P> 0 .05) ,FC cutoff level of 250 μg /g gave a sensitivity and specificity of 50 .0% ,66 .7% ,respectively .Conclusion FC is a surrogate marker for the evaluation of colonic or ileo-colonic CD endoscopic disease activity .The FC ,however ,can not distinct remission period and active period after CD surgery .

Objective To evaluate the clinical significance of CK20 mRNA expression in the blood of gastric cancer patients. Methods Expression of CK20 mRNA was detected by FQ-PCR in preoperative peripheral blood, tumour drainage blood and postoperative peripheral blood in 55 gastric patients and 60 blood donors.Results There was no positive expression of CK20 mRNA of peripheral blood in 60 healthy blood donors.The expression rate of CK20 mRNA was 45.45% in preoperative peripheral blood.The expression rate was higher in stage Ⅲ Ⅳ than stage ⅠⅡ patients ( P

AIM: To evaluate the relationship between uPA and NF-?B p65 expression and its clinical significance in breast cancer. METHODS: The uPA mRNA was measured by real-time fluorescent quantitative PCR in 46 cases of breast cancer tissues and their adjacent counterparts. NF-?B p65 were measured using immunohistochemistry. RESULTS: The expression of uPA gene was elevated in 63% of cases, and there was a strong correlation between NF-?B p65 and uPA expression (r=0.451,P

Objective:To explore the traits of functional connectivity of resting-state networks in patients of schizophrenia with auditory verbal hallucinations (AVH) by using independent component analysis (ICA).Methods:All patients were met the Diagnostic and Statistical Mannal of Mental Disorders,Fourth Edition,Text Revision (DSM-IV-TR) diagnostic criteria for schizophrenia.Thirty schizophrenia patients with frequent AVH (AVH),24 schizophrenia patients without AVH (non-AVH) and 60 healthy controls (HC) matching with age and gender were analyzed by resting functional magnetic resonance imaging.The AVH were assessed by using Hoffman auditory hallucination scale.By using ICA,auditory network (AUN),language network (LAN),salience network (SAN),right front-parietal network (RFP) and default mode network (DMN) were selected as interesting networks for further analyses.Covariance analysis was used to compare the activity and functional connectivity of multiple resting state networks between three groups,and correlation analysis was used to evaluate the relations between abnormalities of brain and the severity of hallucination.Results:Compared to non-AVH,AVH group showed increased activity in left superior temporal gyrus (STG) and left postcentral gyrus (LPG) in the AUN,and showed decreased activity in right anterior cingulate cortex (ACC) in the SAN (P ＜ 0.05,FDR corrected).The severity of AVH group was associated with activity of the left STG (r =0.43,P ＜0.05) and the right ACC (r =-0.48,P ＜0.01).Furthermore,compared to non-AVH group,there were decreased connectivity between LAN and AUN [(-0.29 ±0.21) vs.(-0.16 ± 0.17),P ＜ 0.05,uncorrected],decreased connectivity between SAN and LAN [(-0.09 ± 0.22) vs.(-0.06 ± 0.18),P ＜ 0.05,uncorrected],increased connectivity between SAN and AUN [(0.30 ± 0.18) vs.(0.15 ± 0.24),P ＜ 0.05,uncorrected] in AVH group.Conclusion:There may be aberrant functional connectivities of AUN,LAN and SAN in schizophrenia patients with frequent AVH,and the occurrence of AVH seems to be related to brain areas involved in language production,speech perception and self-monitoring.

PURPOSE: This study is intended to investigate the effects of plants or plant-derived antioxidants on prevention of osteoporosis through the maintenance of reactive oxygen species (ROS) at a favorable level. MATERIALS AND METHODS: In this study, a novel antioxidant, namely 3,4,5-Trihydroxy-N-[4-(5-hydroxy-6-methoxy-pyrimidin-4-ylsulfamoyl)-phenyl]-benzamide (ZXHA-TC) was synthesized from gallic acid and sulfadimoxine. Its effect on osteoblast metabolism was investigated via the detection of cell proliferation, cell viability, production of ROS, and expression of osteogenic-specific genes including runt-related transcription factor 2 (RUNX2), bone sialoprotein (BSP), osteocalcin (OCN), alpha-1 type I collagen (COL1A1), and osteogenic-related proteins after treatment for 2, 4, and 6 days respectively. RESULTS: The results showed that ZXHA-TC has a stimulating effect on the proliferation and osteogenic differentiation of primary osteoblasts by promoting cell proliferation, cell viability, and the expression of genes BSP and OCN. Productions of bone matrix and mineralization were also increased by ZXHA-TC treatment as a result of up-regulation of COL1A1 and alkaline phosphatase (ALP) at the early stage and down-regulation of both genes subsequently. A range of 6.25x10(-3) microg/mL to 6.25x10(-1) microg/mL is the recommended dose for ZXHA-TC, within which 6.25x10(-2) microg/mL showed the best performance. CONCLUSION: This study may hold promise for the development of a novel agent for the treatment of osteoporosis.
Alkaline Phosphatase/metabolism ; Bone Morphogenetic Proteins/pharmacology ; Cell Differentiation/*drug effects ; Cell Proliferation/*drug effects ; Collagen Type I/genetics ; Core Binding Factor Alpha 1 Subunit ; Down-Regulation ; Gallic Acid ; Osteoblasts/*drug effects ; Osteocalcin/metabolism ; Osteogenesis/drug effects ; Osteoporosis/*prevention & control ; Reactive Oxygen Species ; Up-Regulation

OBJECTIVETo investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesis and progression of gastric cancer.

METHODSWe studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and primary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopathological features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.

RESULTSMMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113), less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancer was positively correlated with tumor size, invasive depth, metastasis and TNM staging (P<0.05), but not with differentiation or growth pattern of gastric cancer (P>0.05). Positive correlation of mean MVD with tumor size, invasive depth, metastasis and TNM staging was found (P<0.05), despite no relationship between mean MVD and differentiation of gastric cancer (P>0.05). Mean MVD was dependent on MMP-7 expression in gastric cancer (P<0.05).

CONCLUSIONUpregulated expression of MMP-7 played an important role in carcinogenesis and progression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 expression could be regarded as an effective and objective marker to reflect the biological behaviors of gastric cancer.

Biomarkers, Tumor ; metabolism ; Humans ; Lymphatic Metastasis ; Matrix Metalloproteinase 7 ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; pathology

Neuro-osteological interactions have an important role in the regulation of bone metabolism and regeneration. Neuropeptides combined with porous biphasic calcium phosphates (BCP) using protein adsorption may contribute to the acceleration of bone formation. In the present study, we investigated the effect of BCP combined with nerve growth factor (NGF) on the growth of osteoblasts in vitro and the combinational therapeutic effect on the repair of calvarial defects in vivo. NGF was separated and purified from Chinese cobra venom using a simplified three-step chromatography method. BCP combined with NGF exerted a potent effect on osteoblast differentiation, as evidenced by enhanced cell proliferation, increased ALP activity and the up-regulated expression of osteogenesis-related genes and proteins. Further, combinational therapy with BCP and NGF improved calvarial regeneration, which was superior to treatment with therapy alone, as observed using imageological and morphological examination and histological and immunohistochemical staining. The results confirmed the effect of neuro-osteological interactions through combinatorial treatment with NGF and BCP to promote osteogenesis and bone formation, which may provide an effective and economical strategy for clinical application.
Acceleration ; Adsorption ; Asian Continental Ancestry Group ; Calcium Phosphates ; Cell Proliferation ; Ceramics* ; Chromatography ; Cobra Venoms ; Elapidae* ; Humans ; In Vitro Techniques ; Metabolism ; Methods ; Nerve Growth Factor* ; Neuropeptides ; Osteoblasts ; Osteogenesis ; Regeneration ; Therapeutic Uses*