Vascular endothelial growth factor (VEGF) is one of the most effective angiogenic factors that promote generation of tumor vasculature. VEGF is usually up-regulated in multiple cancers including osteosarcoma and glioma. To further explore the potential molecular mechanism that inhibits tumor growth induced by interference of VEGF expression, we constructed a Lv-shVEGF vector and assessed the efficiency of VEGF silencing and its influence in U2OS cells. The data demonstrate that Lv-shVEGF has high inhibition efficiency on VEGF expression, which inhibits proliferation and promotes apoptosis of U2OS cells in vitro. Our results also indicate that inhibition of VEGF expression suppresses osteosarcoma tumor growth in vivo and reduces osteosarcoma angiogenesis. We also found that the activations of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) were considerably reduced after osteosarcoma cells were treated with Lv-shVEGF. Taken together, our data demonstrate that VEGF silencing suppresses cell proliferation, promotes cell apoptosis, and reduces osteosarcoma angiogenesis through inactivation of PI3K/AKT signaling pathway.

Squamous cell carcinoma (SCC) is one of the most common skin cancers. In the present study, we explored the effects of depletion of murine double minute gene 2 (MDM2) together with overexpression of N-myc downstream-regulated gene 2 (NDRG2) on cutaneous SCC. In order to achieve high efficiency of gene knockdown and overexpression in SCC-13 cells, recombinant adenovirus carrying siMDM2 and NDRG2 expression construct was produced. We found Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 infections inhibit the growth of SCC-13 cells in vitro, and Ad-siMDM2-NDRG2 infection has the highest inhibitory effect. Subcutaneous injections of Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 into SCC-13 xenograft nude mice resulted in the reduction of tumor volume. Moreover, we found that apoptosis protein caspase 3 was up-regulated in the Ad-siMDM2-, Ad-NDRG2-, and Ad-siMDM2-NDRG2-treated groups. Our data indicate that the adenovirus-mediated MDM2 silencing and NDRG2 overexpression can synergistically inhibit local cancer cell proliferation, induce apoptosis, and further prevent metastases of SCC. Our study provides a promising method that can be further developed as a new therapeutic approach against SCC.

The purpose of the study is to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) with pingyangmycin-lipiodol emulsion for the treatment of symptomatic giant hepatic haemangioma. Four hospitals (The Second Hospital of Shandong University, Qilu Hospital of Shandong University, Shandong Provincial Hospital and Jinan Municipal Hospital) participated in this study during 2002-2012. A total of 836 patients with symptomatic giant haemangioma were treated with pingyangmycin-lipiodol emulsion via selective TACE. The patients were followed-up for 12 months-10 years. The effectiveness of the treatment was evaluated by symptom assessments and upper abdominal magnetic resonance imaging or computed tomography. TACE was successfully performed for a total of 1120 lesions in 836 patients. Success rate of the procedure was 100 %. The mean diameter of the haemangiomas was significantly reduced after the interventional therapy (mean diameter 9.6 ± 0.8 vs. 3.6 ± 0.5 cm; P < 0.05). Symptom relief was achieved in all the patients during the follow-up period. No mortality was identified. TACE with pingyangmycin-lipiodol emulsion is a safe, feasible, and effective treatment for the giant symptomatic hepatic haemangioma.

The objective of this study was to analyze the predictive significance of different prognostic factors associated with recurrence and metastasis after the radical resection in patients with hepatolithiasis complicated by intrahepatic cholangiocarcinoma (HLA/IHCC). A total of 138 patients with HLA/IHCC admitted during April 2006-April 2009 were selected for this study and they were divided into two groups, with and without recurrence/metastasis. After a radical resection surgery, the patients were followed up for 5 years to monitor the recurrence and/or metastasis. The general and clinical data of the two groups were analyzed to evaluate the relevant risk factors. The study showed that recurrence/metastasis occurred in 48 patients with a rate of 34.8 %. Recurrence in liver accounted for 85.4 % (41 cases), whereas in lung and bone metastases occurred at rates of 8.3 % (4 cases) and 6.3 % (3 cases), respectively. Univariate analysis revealed that CA19-9, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage of the recurrence/metastasis group were significantly different from those of the non-recurrence/metastasis patients (p < 0.05). The multivariate analysis showed that CA19-9 > 200 U/mL, tumor diameter >5 cm, presence of multiple tumors, lymphatic metastasis, and III-IV AJCC stages were independent risk factors of tumor recurrence and metastasis after the radical surgery (p < 0.05). During the 5 years of follow-up, 65 patients (47.1 %) died, including 31 in the recurrence/metastasis and 34 in the non-recurrence/metastasis groups, accounting for 64.5 % (31/48) and 37.8 % (34/90) of mortality in the two groups, respectively. Thus, the 5-year mortality in the recurrence/metastasis group was significantly higher than that in the non-recurrence/metastasis group (p < 0.05). The CA19-9 antigen, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage were significantly associated with increased risk of post-resection recurrence and metastasis of HLA/IHCC. The massive lymphadenectomy during the surgery and perioperative control of inflammation decreased the risk of recurrence/metastasis and further improved the disease prognosis.

The present study intends to explore the influence of Lgr5 as a marker of tumor stem cells after siRNA interference on the proliferation and invasion of colorectal carcinoma (CRC) and its mechanism. The tissue samples were taken for biopsy from 32 cases of patients and 32 cases of normal subjects by colonoscopy. Real-time quantitative PCR was used to detect the differential expression of Lgr5. After siRNA interference of Lgr5 in CRC cell line CT-26 cells, RT-PCR method was used to detect the mRNA expression level of Lgr5 after interference of CT-26 cells. CCK8 method was used to observe the influence of Lgr5 interference on the proliferation, colony formation, and invasion of CT-26 cells. RT-PCR and Western blot were used to detect the E-cadherin mRNA and protein levels in CT-26 cells. Lgr5 expression level in CRC tissue was significantly higher than that in the corresponding para-carcinoma tissue and the control group, and the differences were statistically significant (P < 0.05). Lgr5 mRNA expression level in tissue with lymph node metastasis was significantly higher than that in the tissue without lymph node metastasis, and the difference was statistically significant (P < 0.05). Compared with the control group, CT-26 cell proliferation, colony formation, and migration capability after Lgr5 siRNA transfection were all significantly reduced, and the differences were statistically significant (P < 0.05). CT-26 cells after Lgr5 interference were found with significantly reduced E-cadherin mRNA and protein levels. Lgr5 facilitates the cell proliferation, colony formation, and migration of colorectal carcinoma, which may be closely related to the expression level of E-cadherin.

Malignant gliomas are rarely curable malignant tumors in the central nervous system. Chlorotoxin (CTX) is a peptide derived from scorpion venom, which can selectively target malignant gliomas. Onconase (Onc) is a small cytotoxic ribonuclease derived from frogspawn that exhibits cytotoxicity against some tumor cells. In the present study, we found that CTX-conjugated Onc (CTX-Onc) shows better anti-tumor effect than the physical mixture of CTX and Onc (CTX + Onc) on the nude mice carrying subcutaneous glioblastoma cell-derived tumor. However, CTX-Onc does not show dose-dependent anti-tumor effect. In addition, apoptosis in tumor tissue does not show significant difference between the treatment groups. Our results confirmed that CTX-Onc has better anti-tumor effect than CTX + Onc and suggest that it can be potentially used for glioma therapy.

Non-homologous end joining (NHEJ) is one of the pathways used to repair the DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as lung cancer susceptibility genes such as the LIG1. However, some studies have generated conflicting results. The aim of this review and meta-analysis was to investigate the association between the LIG1 gene polymorphism and lung cancer risk. Studies focusing on the relationship between the LIG1 gene polymorphisms and susceptibility to lung cancer were selected from several electronic databases, with the last search up to October 25, 2014. Data were extracted by two independent reviewers, and the meta-analysis was performed with STATA version 12.0 software, calculating odds ratios (ORs) with 95 % confidence intervals (95 % CIs). According to the inclusion criteria, we included ten studies with a total of 4012 lung cancer cases and 5629 healthy controls in the meta-analysis. The results showed that the rs156641 polymorphism was significantly associated with lung cancer risk (dominant model: OR 0.694, 95 % CI 0.549-0.878; homozygote model: OR 0.677, 95 % CI 0.526-0.871; heterozygote model: OR 0.712, 95 % CI 0.556-0.913; additive model: OR 0.859, 95 % CI 0.767-0.962), whereas no association was found between rs3730931/rs439132/rs20579 polymorphisms and lung cancer. Our meta-analysis suggested that the rs156641 polymorphism in the LIG1 gene might be associated with an increased risk of lung cancer.

A large proportion of malignant cancers of the stomach are gastric adenocarcinoma type. In spite of many studies, the molecular basis for this cancer is still unclear. Deregulated cell proliferative signaling via Wnt/β-catenin and Hedgehog pathways is considered important in the pathogenesis of many cancers including the gastric cancer. Recent studies identified ZnRF3 protein, which is a E3-ubiquitin ligase and which is either deleted or mutated in cancers, to inhibit Wnt signaling. However, the significance of ZnRF3 in the control of gastric cancer and whether it also regulates Hedgehog signaling pathway, is not known. In the present study, we assessed the expression of ZnRF3 in gastric tumors and paracancerous tissues from 58 patients (44 male and 14 female) of different ages and related this to patient survival. We observed a clear relationship between ZnRF3 expression in paracancerous tissue and tumor size. Also, ZnRF3 expression was much higher in tumors from aged patients. Male patients showed higher mortality than the females. Mechanistic studies using normal gastric cells (GES1) and gastric cancer cells (MGC-803) infected with either AdZnRF3 or AdGFP viral vectors, revealed that ZnRF3 overexpression causes significantly more apoptosis and lowered proliferation of cancer cells. ZnRF3 overexpression led to greatly reduced levels of Lgr5, a component of Wnt signaling and also Gli1, a component of Hedgehog signaling. Thus, ZnRF3 negatively influences both the Wnt and Hedgehog proliferative pathways, and probably this way it negatively regulates cancer progression. These results suggest the importance of normal ZnRF3 function in checking the progression of cancer cell growth and indicate that a lack of this protein can lead to poorer clinical outcomes for gastric cancer patients.

The objective of this study is to determine the diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) in patients with recurrent or residual prostate cancer (PCa) after radical prostatectomy. Studies were systematically searched in the PubMed, EMBASE, Cochrane library, SCI, CBM, CNKI, VIP, Wan Fang, and other databases. Additional studies were manually searched using the references of the retrieved articles. The retrieved deadline was Sep. 6th, 2014. Selection of eligible studies for inclusion was based on the inclusion and exclusion criteria, and the quality of the studies was reviewed based on the QUADAS criteria. The Meta Disc 1.4 and Stata 12.1 software were used for meta-analysis, and a summary receiver operating characteristic curve was constructed. The patient-based pooled weighted estimates of the sensitivity, specificity, diagnostic odds ratio, and 95 % confidence interval were calculated. Seven articles (12 studies) were included in the meta-analysis. The pooled estimates of the sensitivity, specificity, and the area under the curve were 0.88 (95 % CI 0.84-0.91), 0.87 (95 % CI  0.81-0.92), and 0.9391, respectively. The diagnostic odds ratio (DOR) was 50.4 (95 % CI 26.0-97.6) and Q* was 0.8764. DCE-MRI has high sensitivity and specificity in the evaluation of locally recurrent or residual PCa after radical prostatectomy.

This study tried to dissect BAFF/BAFF-R-mediated non-canonical NF-κB signaling in the drug resistance of B-cell non-Hodgkin's lymphoma. FQ-PCR was employ to determine the mRNA expression of BAFF, BAFF-R, Bcl-xL, and RIPK2 in the circulating blood of B-cell non-Hodgkin's lymphoma patients. Further correlation studies were performed with the gene expression in the circulating blood and tumor tissue. MTT assay as used to determine BAFF's role on lymphoma cell proliferation. Western blot was employed to determine protein expression after BAFF stimulation. The mRNA expression of BAFF, BAFF-R, Bcl-xL, and RIPK2 in the circulating blood of the resistant group was higher than that of the non-resistant group, which was statistically significant. The mRNA expression of the target genes was positively correlated. The mRNA expression was positively correlated with disease progression, which was statistically significant. The Bcl-xL mRNA expression in the resistant group was relatively higher than that in the non-resistant group, which was also statistically significant. However, the mRNA expression of other genes only showed increased tendency compared with non-resistant group. There was no significant change between target genes in different tumor tissues. With increased BAFF concentration and prolonged exposure, the proliferation of the tumor cells increased significantly, which was statistically significant. Western blot showed the expression of BAFF, BAFF-R, Bcl-xL, and RIPK2 all increased with increased BAFF concentration, which was also statistically significant. In B-cell, non-Hodgkin's lymphoma, BAFF may activate non-canonical NF-κB signaling to regulate drug resistance.

Gastric cancer has high morbidity and mortality. Identification of patients with high gastric cancer risk at early stage will improve patient prognosis. In this study, we examined two single nucleotide polymorphism (SNP) sites of COX-2 gene in gastric cancer patients and explored the effect of the SNPs on the morbidity of gastric cancer. We found that the SNPs COX-2-1195G/A and COX-2-8473T/C are correlated with the occurrence of gastric cancer, and the patients with variants A and C of the SNPs are liable to have gastric cancer. Our study provides a potential method for screening of susceptible population of gastric cancer for early-stage intervention in patients.

Our objective is to explore the tumor-specific mutated genes by transcriptome sequencing of patients with acute myeloblastic leukemia. 96 patients with subtype M2 acute myeloid leukemia (AML), admitted during January 2007 to January 2012, were selected. Bone marrow and peripheral blood samples from the patients after the first visit and the patients who were improved or alleviated, were subjected to high-throughput sequencing to compare the gene expression. The single nucleotide mutation related to subtype M2 AML was detected. Meanwhile, real-time fluorescent quantitation RT-PCR was used to detect the AML1/ETO fusion gene and its correlation with prognosis after treatment. Among 96 patients, AML1-ETO fusion gene was positive in 52 cases, the positive rate was 54.17 %. The complete relief (CR) rate of AML1-ETO fusion gene positive patients was 84.62 %, and the CR rate of AML1/ETO fusion gene negative patients was 77.27 %; the CR rate of AML1-ETO positive patients was higher than that of patients without the fusion gene, however there was no statistical difference. In the analysis of recurrent gene mutation in AML-M2 patients, IDH2, ASXL1, TET2, JAK1 and JAK2 gene expressions were not significantly different before treatment and after CR, however, IDHI, JAK3, ABL1 and BCR gene expressions were significantly different. In the study of transcriptome in AML-M2 patients, high-throughput sequencing could effectively detect the difference of the gene expression before treatment and after CR. Furthermore, positive expression of AML1-ETO fusion gene had effect on the prognosis of patients.

The aim of this study is to explore the expression and significance of urokinase-type plasminogen activator (u-PA) and vascular endothelial growth factor (VEGF) in gastric cancer, providing a novel insight for the diagnosis and treatment of gastric cancer. The gastric cancer specimens, which were excised from 87 patients and confirmed during July, 2012-July, 2014, were selected as observation group, and the normal tissue next to the tumor (more than 5 cm from the edge of the tumor) from 45 patients were randomly selected as control. u-PA and VEGF were detected by immunohistochemistry for the analysis of the correlation of u-PA and VEGF in two groups. The positive rates of u-PA and VEGF in gastric cancer tissue were 81.61 and 79.31 %, respectively, which were 6.67 and 8.89 % in the control group, respectively. The positive rates in the observation group were obviously higher than those in the control group, and the difference was statistically significant (P < 0.05). Among the 87 gastric cancer tissue samples from the observation group, the positive rates of u-PA and VEGF in the gastric cancer with poor differentiation, lymphatic metastasis, invasion up to serosal layer, and TNM stage III + IV were obviously higher than those in the gastric cancer with high differentiation, non-lymphatic metastasis, invasion not up to the serosal layer, and TNM stage I + II, and the difference was statistically significant (P < 0.05). Among the 87 gastric cancer tissue samples from the observation group, u-PA and VEGF were found to be positive in 60 cases and negative in 7 cases. By comparing the two groups, u-PA and VEGF were positively correlated in gastric cancer tissue (P < 0.05). u-PA and VEGF were highly expressed in gastric cancer tissue, which could be used as the molecular biological indicators to predict the invasion and metastasis potential of gastric cancer. The combination of two factors plays a guiding role in early diagnosis and treatment of gastric cancer.

The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

The Genea052 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through CGH and STR analysis. Pluripotency of Genea052 was demonstrated with 85% of cells expressing Nanog, 87% Oct4, 60% Tra1-60 and 97% SSEA4, a PluriTest Pluripotency score of 27.21, Novelty score of 1.2 and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and any visible contamination.

The Genea047 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea047 was demonstrated with 88% of cells expressing Nanog, 95% Oct4, 59% Tra1-60 and 99% SSEA4, a PluriTest Pluripotency score of 30.86, Novelty score of 1.23 and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and any visible contamination.

Aggressive adult granulosa cell tumor (AGCT) of the ovary remains uncommon. We report a case of aggressive AGCT of the ovary who had rapid recurrence at two months after surgery. A patient was referred for further examination of a pelvic tumor. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. In the areas showing a sarcomatoid pattern, the mitotic count were 25/10 HPFs, and the mitoses were most prominent in foci composed of pleomorphic cells with enlarged and bizarre nuclei. In some areas, tumor cells with relatively uniform nuclei proliferated in a trabecular pattern. The mitotic count was 4/10 HPFs. Tumor cells were diffusely positive for α-inhibin. She was diagnosed as having aggressive AGCT. The Ki-67 labeling index in the sarcomatoid AGCT was higher (40%) than that in the areas of typical AGCT (3%). Immunostaining for p53 in the sarcomatoid AGCT was almost strongly positive, but that in typical AGCT was negative. Two months later after the initial surgery, a recurrent abdominal 12 cm-sized mass developed after performing adjuvant chemotherapy consisting of paclitaxel and carboplatin. She died of the disease at 3 months after initial surgery. A markedly higher mitotic count, a higher Ki-67 labeling index, and strong immunoreactivity of p53 in AGCT suggests highly malignant potential. In such a case, a careful follow-up is warranted due to the possibility of rapid recurrence.

Pheochromocytoma is a tumor originating in the chromaffin cells. These tumors secrete catecholamines which act on target organs and cause hypertensive crises. They are rare during pregnancy, and a differential diagnosis must be carried out mainly with pregnancy-induced hypertension.

The ovaries accessories, ectopic and supernumerary represent a rare gynecological disorder; incidence ranges from 129,000 to 1:700,000 cases.

Cystic hepatic metastases arising from malignant melanoma are extremely rare, with the few such cases reported in the literature to date describing indeterminate imaging findings, being focused more on computed tomography. To the best of our knowledge, there is no prior report describing contrast-enhanced ultrasound findings of a solitary cystic liver metastasis from a primary rectal melanoma. We herein describe a case of a 41-year-old patient with a rectal melanoma, in whom the first manifestation of disease was a solitary complex cystic liver metastasis incidentally detected by ultrasound. On admission, our patient was free of specific symptoms and his laboratory test was normal. In this setting, contrast-enhanced ultrasound showed some distinctive features that helped us to make the correct diagnosis, confirmed subsequently by FNAC examination, thus allowing to provide the correct management for our patient. Although cystic metastases are rare, knowledge of CEUS imaging findings will be invaluable for radiologists and other medical subspecialties that may face such cases in the future in helping to provide adequate management for affected patients.