Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction.

OBJECTIVES: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). METHODS: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. RESULTS: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. CONCLUSION: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

New sonographic morphology score for the differentiation of malignant from benign ovarian tumors.

AIM: The aim of this study was to explore the efficacy of a new sonographic morphology score (SMS) to differentiate malignant from benign ovarian tumors. METHODS: Data on 84 ovarian tumors in patients hospitalized in our hospital between 2013 and 2014 were retrospectively analyzed. We established a new sonographic morphology score for ovarian tumors based on volume and structure scores. The efficacy of the new SMS was compared with that of Ueland's index (the old SMS). Receiver-operator curves (ROC) of the two SMS were constructed, and the areas under the curve were calculated and compared. The ROC of the new SMS was also compared with those for the patients' CA-125 and CA-72-4 levels. RESULTS: The area under the ROC of the new SMS for ovarian tumors was 0.836, while for the old SMS for ovarian tumors it was 0.709. By Z-test (Z = 2.452, P = 0.0384), there was a significant difference between the new SMS and the old SMS in the diagnosis of ovarian tumors. There was no significant difference in the area under the ROC between the new SMS and CA-125 and CA-72-4 in the diagnosis of ovarian tumors. With a cut-off value of 6, the sensitivity, specificity, positive prognostic value, and negative prognostic value of the new SMS were 0.797, 0.85, 0.944, and 0.567, respectively. CONCLUSION: The new SMS may be used to differentiate malignant ovarian carcinomas from benign tumors except in the case of ovarian thecoma.

Preoperative ultrasound features as prognostic factors for patients with hepatocellular carcinoma.

PURPOSE: Ultrasound is the most common imaging tool used to scan the tumours of hepatic carcinoma patients. However, very few studies have been performed to evaluate ultrasound imaging features for predicting tumour prognosis. Therefore, the goal of the current study was to evaluate preoperative ultrasound characteristics as prognostic factors that could affect survival rate after liver resection for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 104 HCC patients who underwent resection were retrospectively reviewed with regard to their clinical data, preoperative ultrasound characteristics, and survival rate. Preoperative ultrasound parameters included cirrhosis, tumour site, size, echo pattern, portal vein thrombosis, intra-tumour blood flow signal, peak systolic velocity (V max), and resistance index (RI). The Kaplan-Meier method was used to calculate survival. Pre-resection prognostic factors were assessed using univariate log-rank test and a multivariate Cox proportional hazards model. RESULTS: The median survival was 37 months. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 78.85, 53.85, and 26.92 %, respectively, and the overall survival (OS) rates at 1, 3, and 5 years were 85.58, 69.23, and 46.15 %, respectively. On univariate analysis, shorter survival was associated with mixed echo pattern, larger tumour size, portal vein thrombus, affluent flow signal, and higher V max. Application of the Cox multivariate proportional hazards model indicated that tumour size and blood flow signal in the tumours were independent prognostic factors. CONCLUSIONS: The overall survival for HCC patients undergoing hepatic resection can be stratified on a sonographic basis of tumour size and intra-nodular vasculature. These prognostic factors may be useful to determine appropriate treatment for HCC patients.

Common variation rs6983267 at 8q24.1 and risk of colorectal adenoma and cancer: evidence based on 31 studies.

Genome-wide association studies have identified 8q24.21-rs6983267 as a new colorectal cancer (CRC) and colorectal adenoma (CRA) susceptibility locus in populations of European descent. Since then, the relationship between 8q24.21-rs6983267 and CRC/CRA has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency and derive a more precise estimation of the relationship, we conducted a meta-analysis of 31 studies, including 51,293 cases and 58,962 controls for CRC, and 8,148 cases and 17,065 controls for CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio of G variant for CRC was 1.18 (95% CI, 1.16-1.21; P < 10(-5)) and 1.17 (95% CI, 1.11-1.23; P < 10(-5)) for CRA. Significant results were observed using dominant or recessive genetic model for the polymorphism. In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians and Caucasian populations; while no significant associations were detected among African Americans. After stratifying by sample size and control source, significant associations were also obtained. This meta-analysis suggests that the 8q24.21-rs6983267 polymorphism is associated with CRC/CRA susceptibility, but these associations vary in different ethnic populations.

Application Research Progress of Nanomaterial Graphene and its Derivative Complexes in Tumor Diagnosis and Therapy.

Functional nanomaterial graphene and its derivatives have attracted considerable attention in many fields because of their unique physical and chemical properties. Most notably, graphene has become a research hotspot in the biomedical field, especially in relation to malignant tumors. In this study, we briefly review relevant research from recent years on graphene and its derivatives in tumor diagnosis and antitumor therapy. The main contents of the study include the graphene-derivative diagnosis of tumors in the early stage, graphene quantum dots, photodynamics, MRI contrast agent, acoustic dynamics, and the effects of ultrasonic cavitation and graphene on tumor therapy. Moreover, the biocompatibility of graphene is briefly described. This review provides a broad overview of the applications of graphene and its derivatives in tumors. Conclusion, graphene and its derivatives play an important role in tumor diagnosis and treatment.

MRI appearances of stage IA ovarian carcinoma.

OBJECTIVE: To analyze the MRI findings of stage IA ovarian cancer. METHODS: The data on age distribution, clinical symptoms at onset, CA125 detection, MRI findings, including tumor volume, structure, diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and enhancement, etc., of the patients with stage IA ovarian cancer, who were admitted to Nantong tumor Hospital between 2013 and 2020 were analyzed retrospectively. RESULTS: Only 11 cases of stage IA ovarian cancer were recorded. The age of patients was 30-67 (average 52) years. The initial symptoms were mostly lower abdominal distension and abdominal pain. CA125 was 90% positive. MRI features 1. Large pelvic mass with a volume range of 23-2,009 cm3 (average 669 cm3). 2. Five cases of cyst type (with plaque-like, papillary, or mural nodule vegetations), two cases of cystic-solid mixed type (with thickened septum or wall), and four cases of solid type. 3. DWI diffusion was limited, and ADC was reduced on all solid portions (vegetation, septa, and cyst wall). 4. The solid parts were significantly enhanced on T1-enhanced MRI. 5. There was no metastasis in the pelvic cavity, and a few ascites (negative tumor cells) in three patients. CONCLUSIONS: MRI characteristics of stage IA ovarian carcinomas were large tumors, cystic, cystic-solid, or solid; solid portion limited diffusion on DWI and low ADC; enhancement of the cyst wall, vegetation, and septa; no pelvic metastasis.

Real-world treatment patterns and survival for locally advanced esophageal squamous cell carcinoma.

The "real world" treatment mode and clinical efficacy of locally advanced esophageal squamous cell carcinoma (LAESCC) are unclear. Meanwhile, the role of immunotherapy in the clinical practice is also puzzling. We conducted the research to investigate the statue of "real world" LAESCC. The clinical data of patients with locally advanced esophageal squamous cell carcinoma which met the criteria from January 2010 to December 2019 have been retrospectively analyzed, and the distribution of clinical treatment patterns has been analyzed. They cover such aspects as dfferences in survival time and further analysis of the differences in overall survival (OS) and progression-free survival (PFS) between patients who received immunotherapy and those who did not receive immunotherapy. What is more, Cox risk regression model has also been used to evaluate the risk factors affecting the prognosis of LAESCC. The cases of a total of 5328 newly diagnosed patients with esophageal cancer were collected, and a total of 363 patients were included in the study, with a median age of (46.2 ± 7.8) years old; 84 (23.1%) and 279 (76.9%) patients received 1L and ≥ 2L, respectively; Concurrent chemoradiotherapy (74.1%) and paclitaxel combined with platinum-based chemotherapy (14.3%) were the main first-line treatment options; fluorouracil combined with cisplatin regimen-based chemotherapy (63.8%) was the main treatment option for ≥ 2L, of which 69 patients (25.3%) received immunization treatment; OS of patients with 1 line of therapy and ≥ 2L were (22.4 ± 7.2) months and (38.7 ± 8.5) months, respectively, and the comparison between groups was statistically significant (P < .05); among 69 patients with ≥ 2L who received immunotherapy, PFS and The OS was (14.6 ± 6.9) and (45.3 ± 9.7) respectively, and the comparison between the groups was statistically significant (all P < .05). Cox multivariate analysis has shown that clinical stage, immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are the main factors affecting OS. and immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are independent factors affecting PFS. Concurrent chemoradiotherapy is currently one of the standard treatments for LAESCC, and most patients are still willing to receive second-line or above treatments. Adding immunotherapy to standard treatment modalities may further optimize clinical treatment modalities and improve patient outcomes.

CTHRC1 is upregulated by promoter demethylation and transforming growth factor-ß1 and may be associated with metastasis in human gastric cancer.

The gene, collagen triple helix repeat containing 1 (CTHRC1), has been reported to increase in several kinds of human solid cancers and is associated with tumor invasion and metastasis. To date, the expression and function of CTHRC1 in gastric cancer (GC) have not been reported. The aim of this study was to investigate the expression levels and regulatory transcription mechanisms of CTHRC1 in GC. Immunohistochemical analysis revealed that CTHRC1 expression was markedly increased in carcinoma compared with normal gastric mucosa, chronic atrophic gastritis, and intestinal metaplasia (P < 0.05 for all), and this overexpression in tumor was related to depth of tumor invasion. Moreover, RNA interference-mediated knockdown and ectopic expression of CTHRC1 showed that CTHRC1 promoted tumor cell invasion in vitro. We then investigated the mechanisms underlying the aberrant expression of CTHRC1 in GC and found that CTHRC1 expression was restored after GC cell lines were treated with the demethylating agent, 5-aza-2'-deoxycytidine. Transforming growth factor-ß1 led to an increase in levels of CTHRC1 mRNA and protein. Overall, our data revealed that the upregulated expression of CTHRC1 in gastric carcinogenesis contributes to tumor cell invasion and metastasis, and promoter demethylation and transforming growth factor-ß1 may co-regulate the expression of CTHRC1.

CT Imaging Research Progress in COVID-19.

The highly contagious novel Coronavirus Disease 2019 (COVID-19) broke out at the end of 2019 and has lasted for nearly one year, and the pandemic is still rampant around the world. The diagnosis of COVID-19 is on the basis of the combination of epidemiological history, clinical symptoms, and laboratory and imaging examinations. Among them, imaging examination is of importance in the diagnosis of patients with suspected clinical cases, the investigation of asymptomatic infections and family clustering, the judgment of patient recovery, rediagnosis after disease recurrence, and prognosis prediction. This article reviews the research progress of CT imaging examination in the COVID-19 pandemic.

Genetic Variation and Preliminary Indications of Divergent Niche Adaptation in Cryptic Clade II of Escherichia.

The evolution, habitat, and lifestyle of the cryptic clade II of Escherichia, which were first recovered at low frequency from non-human hosts and later from external environments, were poorly understood. Here, the genomes of selected strains were analyzed for preliminary indications of ecological differentiation within their population. We adopted the delta bitscore metrics to detect functional divergence of their orthologous genes and trained a random forest classifier to differentiate the genomes according to habitats (gastrointestinal vs external environment). Model was built with inclusion of other Escherichia genomes previously demonstrated to have exhibited genomic traits of adaptation to one of the habitats. Overall, gene degradation was more prominent in the gastrointestinal strains. The trained model correctly classified the genomes, identifying a set of predictor genes that were informative of habitat association. Functional divergence in many of these genes were reflective of ecological divergence. Accuracy of the trained model was confirmed by its correct prediction of the habitats of an independent set of strains with known habitat association. In summary, the cryptic clade II of Escherichia displayed genomic signatures that are consistent with divergent adaptation to gastrointestinal and external environments.

HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level.

Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.

[Effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors: a meta-analysis].

OBJECTIVE: To investigate the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors. METHODS: A search of studies in PubMed and MedLine (from 1999 to 2008) was performed to assess the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors. The articles were retrieved with the entries of "gastrointestinal stromal tumors", "imatinib", "c-kit" and "mutation". A meta-analysis was performed to assess the data included. RESULTS: A total of 15 articles were collected in this analysis. No significant differences was found in incidence of mitoses (> 5/50 HPF) between the patients with wild type c-kit (wild type group) and the ones with mutated c-kit (mutation group) (P = 0.710); tumor recurrence and metastasis rate after surgery was significant higher in the mutation group than that in wild type group (P = 0.010); as for imatinib response with different c-kit mutation types, the results showed the incidence of clinical response (complete response + partial response) was significantly higher in mutation group than that in wild type group (P = 0.009), but the imatinib resistance rate was lower in mutation group (P = 0.000); three studies provided data for imatinib resistance with c-kit second mutations, the results showed the second mutations mainly focus on exon 13, 14, 17. CONCLUSIONS: C-kit mutation is related closely with the incidence of recurrence and metastasis in GIST after surgery. The mutations of c-kit influences the therapeutic effects of imatinib.

Combination of Sonographic Morphology Score and Tumor Markers for Detecting Postoperative Recurrent Pelvic Ovarian Carcinoma: Compared With MRI Assessment.

To assess the efficacy of the combination of sonographic morphology score (SMS) with CA125 and HE4 for detecting recurrent pelvic ovarian carcinoma (OC). Data of 58 OC patients treated in our hospital between 2014 and 2016 were analyzed. After cytoreductive surgery and routine chemotherapy, all patients were followed up by transvaginal ultrasound examination (SMS for pelvic masses based on volume and structure scores) and tumor marker (serum CA125 and HE4) detection. Clinical diagnosis of recurrent OC was based on physical examination, magnetic resonance imaging, and punctured pathology for pelvic masses. Receiver operating characteristic (ROC) curves of SMS and the tumor markers were generated, and areas under the curve (AUC) values were assessed. There were 26 patients with tumor recurrence and 32 cases with no recurrence. Magnetic resonance imaging had 100% sensitivity and specificity. The areas under the ROC curves of SMS, CA125, HE4, and SMS-CA125-HE4 were 0.816, 0.825, 0.737, and 0.903, respectively. There was no significant difference in AUC values between SMS and CA125 or HE4. There were significant differences in AUC values between SMS-CA125-HE4 and SMS (Z = 2.48, P = 0.042), CA125 (Z = 2.38, P = 0.046), and HE4 (Z = 6.48, P = 0.016), respectively. With a cutoff value of SMS, 5; CA125, 35 U/mL; HE4, 105 pmol/L, the sensitivity, specificity, positive prognostic value, and negative prognostic value of SMS-CA125-HE4 for recurrent OC assessment were 0.9231, 0.8438, 0.8276, and 0.931, respectively. SMS-CA125-HE4 was correlated with recurrent OC (χ = 30.7428, P < 0.0001). Ultrasound combined with tumor markers may improve the diagnostic efficiency of recurrent OC.

CD36 inhibits ß-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis.

The diverse expression pattern of CD36 reflects its multiple cellular functions. However, the roles of CD36 in colorectal cancer (CRC) remain unknown. Here, we discover that CD36 expression is progressively decreased from adenomas to carcinomas. CD36 loss predicts poor survival of CRC patients. In CRC cells, CD36 acts as a tumor suppressor and inhibits aerobic glycolysis in vitro and in vivo. Mechanically, CD36-Glypcian 4 (GPC4) interaction could promote the proteasome-dependent ubiquitination of GPC4, followed by inhibition of ß-catenin/c-myc signaling and suppression of downstream glycolytic target genes GLUT1, HK2, PKM2 and LDHA. Moreover, disruption of CD36 in inflammation-induced CRC model as well as ApcMin/+ mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-ß-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.

High-speed photographic observation of the sonication of a rabbit carotid artery filled with microbubbles by 20-kHz low frequency ultrasound.

The aim of this study is to assess the physical damage of cavitation effects induced by low frequency ultrasound and microbubbles (MBs) to an in vitro vessel. A rabbit carotid artery filled with SonoVue MBs and methylene blue was irradiated with 20-kHz ultrasound, and the results were recorded by high-speed photography at 3000 frames per second. The carotid artery filled with MBs experienced a slight tremor during ultrasonication. Six intermittent blue flow events occurred in two places on the artery wall during the 5-s process. The duration of each leakage event was 90-360ms with an average of 200ms. Hematoxylin-eosin (H-E) staining demonstrated the separation of the carotid artery elastic membrane, local blood vessel wall defects and hole formation, and the surface of the ruptured area was rough and irregular. Another carotid artery was filled with a 0.9% NaCl solution and methylene blue as a control and irradiated with 20-kHz ultrasound. No blue liquid flow was seen, and no holes in the vessel were observed. H-E staining revealed intact vascular endothelial cells and smooth muscles with no vascular wall defects. Low-frequency ultrasound combined with MBs can cause a vessel to rupture and holes to form in a short time. High-speed photography is useful for observing transient changes caused by the effects of ultrasound cavitation on an in vitro vessel.

Spiral computed tomography evaluation of rabbit VX2 hepatic tumors treated with 20 kHz ultrasound and microbubbles.

The aim of the present study was to explore the therapeutic effect of 20 kHz ultrasound (US) and microbubbles (MBs) on rabbit VX2 liver tumors by spiral computed tomography (CT) scanning. A total of 16 New Zealand rabbits with hepatic VX2 tumors were divided into four groups: Control, MB, low-frequency US and US + MB. The treatment effect was evaluated by spiral CT scanning prior to, during and following treatment (at 0 weeks and the end of 1 and 2 weeks). The tumor growth rate was recorded. The specimens of VX2 tumors were collected for histological examination and transmission electron microscopy (TEM). No significant differences were observed between tumor areas measured by CT and pathology after 2-week treatment (P>0.05). The mean tumor growth rates in the control, MB, US and US + MB groups after 2 weeks of treatment were 385±21, 353±12, 302±14 and 154±9%, respectively (P<0.05, US + MB vs. the other three groups). Hematoxylin and eosin staining in the US + MB group revealed coagulation necrosis, interstitial hemorrhage and intravascular thrombosis. In the control, MB and US groups, tumor cells exhibited clear nuclear hyperchromatism. TEM of US + MB revealed vascular endothelial cell wall rupture, widened endothelial cell gaps, interstitial erythrocyte leakage and microvascular thrombosis, while intact vascular endothelial cells and normal erythrocytes in the tumor vessels were observed in the control, MB and US groups. A combination of 20 kHz US and MBs may effectively inhibit rabbit VX2 tumors. Spiral CT scanning is an ideal method to evaluate the US treatment on rabbit tumors.

The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and microbubbles on rabbit hepatic tumors.

OBJECTIVE: Low-frequency ultrasound (US) in combination with microbubbles (MBs) is able to inhibit the growth of VX2 rabbit liver tumors. In this study, we investigated the feasibility of using percutaneous ethanol injection (PEI) followed by low-frequency ultrasound and microbubbles (USMB) to inhibit VX2 tumor growth. METHODS: Eighteen New Zealand rabbits with hepatic VX2 tumors were divided into three groups: PEI, low-frequency ultrasound and MBs followed by PEI (USMB + PEI), and PEI followed by USMB (PEI + USMB). PEI was performed by ultrasound-guided injection of 95% anhydrous alcohol into internal liver tumors in rabbits twice a week for 2 weeks. The US parameters were 20 kHz, 2 W/cm(2), 40% duty cycle, 5 min, and once every other day for 2 weeks. Magnetic resonance imaging (MRI) was used to observe tumors before and after treatment, to examine changes in the tumors, and to measure the diameters of the tumors. All animals were followed up for 180 days after tumor implantation. Autopsy was performed at the end of the scheduled follow-up or immediately after death. Anatomically observed metastatic sites included the liver, lung, abdomen, and pelvic cavity. The survival time of all rabbits was recorded. RESULTS: After 4 weeks of treatment, on MRI, the tumor diameters in the PEI, USMB + PEI, and PEI + USMB groups were 8.33 ± 1.83, 19 ± 2.61, and 4.5 ± 1.22 mm, respectively. There was a significant difference in tumor size indicated by MRI in the three groups. Tumor size was smaller in the PEI + USMB group than in the PEI and USMB + PEI groups, with t = 4.54, p = 0.0062, and t = 16.38, p < .0001, respectively. The PEI + USMB group showed the fewest metastasis sites (χ(2) = 11.7333, p = 0.0194) and the longest survival period (χ(2) = 7.448, p = 0.0241). CONCLUSION: Percutaneous ethanol injection followed by low-frequency ultrasound and microbubbles can be effective in inhibiting rabbit liver tumors and prolonging survival time.

[TALEN-mediated MYH9 Knock-down and its influence on cell cycle and apoptosis of MGC803 cell line].

OBJECTIVE: To construct a MYH9 gene knockout model in MGC803 cell line using transcription activator-like effector nuclease (TALEN) and observe its effect on cell cycle and apoptosis. METHODS: According to FastTALE(TM) TALEN Kit, we designed TALEN pairs and constructed the plasmids targeting to MYH9 gene. After detecting their activity in MGC803 cells by plasmid transfection, DNA sequencing, RT-PCR and western blot, we selected the monoclonal cells and studied the changes in the cell cycle and apoptosis. RESULTS: MYH9 gene could not be knocked out but knocked down in selected MGC803 monoclonal cells, which caused cell cycle arrested at G2/M phase (P<0.05) and a significant increase in the cell number with early apoptosis (P<0.01). CONCLUSION: We successfully generated a MYH9 knockdown model in MGC803 cell lines by TALEN, which could be in favor of MYH9 function study in gastric cancer.

Analysis of the predictive efficiency of S100P on adverse prognosis and the pathogenesis of S100P-mediated invasion and metastasis of colon adenocarcinoma.

Elevated expression of S100P has been detected in several tumor types. To analyze the potential use of S100P for the prediction of colorectal cancer (CRC) metastasis and prognosis, S100P expression was detected in 125 patients with colon adenocarcinoma by immunohistochemistry, followed by correlation and survival analysis. High S100P expression was correlated with metastasis, as demonstrated by clinically relevant data, and predicted poor survival more effectively than preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in colon adenocarcinoma. Stable S100P knockdown CRC cell lines were established to elucidate the relationship between S100P expression and tumor progression in vitro and in vivo. S100P knockdown resulted in reductions in the invasiveness and metastasis of CRC cells. Xenograft growth in nude mice also demonstrated that down-regulated S100P dramatically inhibited peritoneal metastasis of CRC cells. S100P promoted the invasion and metastasis of CRC by activating RAGE/ERK signaling and promoting the epithelial-mesenchymal transition (EMT). RAGE was found to be crucial for S100P-mediated EMT in colon cancer. Knockdown of RAGE in S100P-overexpressing colon cancer cells dramatically suppressed EMT process. Our results indicate that overexpression of S100P is related with an invasive and metastatic phenotype of CRC which is EMT-involved and RAGE dependent.