MicroRNA-1231 exerts a tumor suppressor role through regulating the EGFR/PI3K/AKT axis in glioma.

PURPOSE: MicroRNAs (miRNAs) have been shown to be involved in the initiation and progression of glioma. However, the underlying molecular mechanisms are still unclear. METHODS: We performed microarray analysis to evaluate miRNA expression levels in 158 glioma tissue samples, and examined miR-1231 levels in glioma samples and healthy brain tissues using qRT-PCR. In vitro analyses were performed using miR-1231 mimics, inhibitors, and siRNA targeting EGFR. We used flow cytometry, CCK-8 assays, and colony formation assays to examine glioma proliferation and cell cycle analysis. A dual luciferase reporter assay was performed to examine miR-1231 regulation of EGFR, and the effect of upregulated miR-1231 was investigated in a subcutaneous GBM model. RESULTS: We found that miR-1231 expression was decreased in human glioma tissues and negatively correlated with EGFR levels. Moreover, the downregulation of miR-1231 negatively correlated with the clinical stage of human glioma patients. miR-1231 overexpression dramatically downregulated glioma cell proliferation, and suppressed tumor growth in a nude mouse model. Bioinformatics prediction and a luciferase assay confirmed EGFR as a direct target of miR-1231. EGFR overexpression abrogated the suppressive effect of miR-1231 on the PI3K/AKT pathway and G1 arrest. CONCLUSIONS: Taken together, these results demonstrated that EGFR is a direct target of miR-1231. Our findings suggest that the miR-1231/EGFR axis may be a helpful future diagnostic target for malignant glioma.

MicroRNA-105 inhibits human glioma cell malignancy by directly targeting SUZ12.

Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. MicroRNAs are a class of small noncoding RNAs that function as regulators of gene expression. Accumulating evidence shows that microRNAs are associated with tumorigenesis and tumor progression. In this study, we found that miR-105 is significantly downregulated in glioma tissues and glioma cell lines. We identified suppressor of Zeste 12 homolog as a novel direct target of miR-105 and showed that suppressor of Zeste 12 homolog protein levels were inversely correlated with the levels of miR-105 expression in clinical specimens. Overexpression of miR-105 inhibited cell proliferation, tumorigenesis, migration, invasion, and drug sensitivity, whereas overexpression of suppressor of Zeste 12 homolog antagonized the tumor-suppressive functions of miR-105. Taken together, our results indicate that miR-105 plays a significant role in tumor behavior and malignant progression, which may provide a novel therapeutic strategy for the treatment of glioma and other cancers.

Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression.

Glioma occurs due to multi-gene abnormalities. Neuropilin-1 (NRP-1), as a transmembrane protein, involves in glioma proliferation, invasion, and migration, as well as tumor angiogenesis. The cytoplasmic protein, GAIP/RGS19-interacting protein (GIPC1), could regulate the clathrin-vesicles trafficking and recycling. Here, we show that NRP-1 co-localizes and co-immunoprecipitates with GIPC1, and the C-terminal SEA-COOH motif of NRP-1 interacts specially with the named from three proteins: PSD-95 (a 95 kDa protein involved in signaling at the post-synaptic density), DLG (the Drosophila melanogaster Discs Large protein) and ZO-1 (the zonula occludens 1 protein involved in maintenance of epithelial polarity) (PDZ) domain of GIPC1 in glioma cells. Knockdown of GIPC1 by small interfering RNA (siRNA) significantly reduces the proliferation and invasion of glioma cells in vitro and increases its apoptosis. Furthermore, si-GIPC1 prevents the action of adaptor proteins adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1) and p130Cas and inhibits the downstream kirsten rat sarcoma viral oncogene homolog (KRAS)-ERK signaling pathway. This study demonstrated that NRP-1/GIPC1 pathway plays a vital role in glioma progression, and it is a potential important target for multi-gene combined therapeutics.

Extraction, Chemical Composition, and Antifungal Activity of Essential Oil of Bitter Almond.

The essential oil from the powder residual of dried bitter almond, a novel and environmentally-friendly fungicide, was successfully extracted in a 0.7% yield by hydro-distillation under optimized conditions. The chemical composition of bitter almond essential oil (BAEO) was analyzed by gas chromatography-mass spectrometry (GC-MS). Twenty-one different components representing 99.90% of the total essential oil were identified, of which benzaldehyde (62.52%), benzoic acid (14.80%), and hexadecane (3.97%) were the most abundant components. Furthermore, the in vitro and in vivo antifungal activities of BAEO against common plant pathogenic fungi were evaluated by the mycelium linear growth rate method and pot test, respectively. It was documented that 1 mg/mL of BAEO could variously inhibit all tested pathogenic fungi with the inhibition rates of 44.8%~100%. Among the tested 19 strains of fungi, the median effective concentration (EC50) values of BAEO against Alternaria brassicae and Alternaria solani were only 50.2 and 103.2 µg/mL, respectively, which were higher than those of other fungi. The in vivo antifungal activity of BAEO against Gloeosporium orbiculare was much higher than Blumeria graminis. The protective efficacy for the former was up to 98.07% at 10 mg/mL and the treatment efficacy was 93.41% at 12 mg/mL. The above results indicated that BAEO has the great potential to be developed as a botanical and agricultural fungicide.

Functional outcome and postoperative complications after the microsurgical removal of large vestibular schwannomas via the retrosigmoid approach: a meta-analysis.

For large (≥30 mm) or giant (≥40 mm) vestibular schwannomas (VSs) for which microsurgical removal is the main treatment option, complete tumour resection and the preservation of acceptable facial nerve function can be safely and successfully achieved via the retrosigmoid approach. We performed a meta-analysis to provide a reliable estimate of functional outcome and postoperative complications for patients treated surgically for large VSs. We conducted a comprehensive search in Pubmed, Embase and the Chinese National Knowledge Infrastructure (CNKI) databases to identify publications that included only patients in whom the VSs were >3.0 cm in maximal diameter and microsurgically removed by a retrosigmoid approach. Pooled estimates of proportions with corresponding 95 % confidence intervals were calculated using the Freeman-Tukey double arcsine transformation. This meta-analysis revealed that the pooled proportion of gross total resections was 79.1 % (95 % CI, 64.2-90.8 %; I (2) = 95.4 %). By combining microsurgical techniques with continuous electrophysiological monitoring, the anatomical preservation of the facial nerve at the end of surgery was achieved in 88.8 % (95 % CI, 83.6-93.2 %; I (2) = 76.1 %) of the patients. The pooled proportion of good postoperative facial nerve function (House-Brackmann (HB) grades I-II) was 62.9 % (95 % CI, 50.0-74.9 %; I (2) = 91.1 %). Cerebrospinal fluid leakage was reported in 7.8 % (95 % CI, 4.8-11.4 %; I (2) = 49.8 %) of the patients. The mortality rate was 0.87 % (95 % CI, 0.22-1.78 %; I (2) = 4.9 %). Our meta-analysis revealed that for large VSs, very favourable results can be obtained using the retrosigmoid approach with minimal mortality, especially with respect to anatomical and functional facial nerve preservation.

Skull base reconstruction using in situ bone flap in patients with pituitary adenomas treated by endoscopic endonasal approach.

Objective: The objective of this study is to study the effect of in situ bone flap (ISBF) repositioning, a recently proposed rigid skull base reconstruction technique, on patients diagnosed with pituitary adenoma undergoing endoscopic endonasal approach (EEA). Method: A retrospective analysis was conducted on 188 patients with pituitary adenomas who underwent EEA from February 2018 to September 2022. Patients were divided into the ISBF group and non-ISBF group, according to whether ISBF was used during skull base reconstruction. Results: Of the 75 patients in the non-ISBF group, 6 had postoperative cerebrospinal fluid (CSF) leakage (8%), while only 1 of 113 patients in the ISBF group (0.8%) had postoperative CSF leakage, indicating that the incidence of postoperative CSF leakage in the ISBF group was significantly lower than that in the non-ISBF group (P = 0.033). In addition, we also found that the postoperative hospitalization days of patients in the ISBF group (5.34 ± 1.24) were significantly less than those in the non-ISBF group (6.83 ± 1.91, P = 0.015). Conclusion: ISBF repositioning is a safe, effective, and convenient rigid skull base reconstruction method for patients with pituitary adenoma treated by EEA, which can significantly reduce the rate of postoperative CSF leakage and shorten postoperative hospital stays.

The contribution of the ABCG2 C421A polymorphism to cancer susceptibility: a meta-analysis of the current literature.

BACKGROUND: ABCG2, also known as BCRP, is a half ATP-binding cassette (ABC) transporter that localizes to plasma membranes. Recently, a number of studies have investigated the relationship between the C421A polymorphism in ABCG2 and cancer risk in multiple populations and various types of cancers; however, this relationship remains unclear. Therefore, we performed a meta-analysis to further explore this association. METHODS: The meta-analysis incorporated 10 studies involving a total of 3593 cases and 5875 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on the date extracted from the studies to evaluate the strength of association. We also analyzed the heterogeneity and sensitivity of each report and the publication bias of the studies. RESULTS: Overall, our results showed that there appeared to be a significant association between the ABCG2 C421A polymorphism and decreased cancer susceptibility (heterozygote-AC versus CC: OR = 0.759, 95%CI = 0.620-0.930; dominant effects model-AA/AC versus CC: OR = 0.771, 95%CI = 0.634-0.938; additive effects model-A allele versus C allele: OR = 0.809, 95%CI = 0.687-0.952). Similarly, decreased cancer risk was also found after stratification of the SNP data by cancer type, ethnicity and source of controls in heterozygote model, dominant effects model and additive effects model. CONCLUSIONS: We found that the ABCG2 C421A polymorphism is a protective factor for developing cancer. The same relationship was found when the studies were stratified by cancer type, ethnicity and source of controls.

The TERT rs2736100 polymorphism and cancer risk: a meta-analysis based on 25 case-control studies.

BACKGROUND: The association between the TERT rs2736100 single nucleotide polymorphism (SNP) and cancer risk has been studied by many researchers, but the results remain inconclusive. To further explore this association, we performed a meta-analysis. METHODS: A computerized search of PubMed and Embase database for publications on the TERT rs2736100 polymorphism and cancer risk was performed and the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis and assessment of bias were performed in our meta-analysis. RESULTS: A significant association between the TERT rs2736100 polymorphism and cancer susceptibility was revealed by the results of the meta-analysis of the 25 case-control studies (GG versus TT: OR = 1.72, 95% CI: 1.58, 1.88; GT versus TT: OR = 1.38, 95% CI: 1.29, 1.47; dominant model-TG + GG versus TT: OR = 1.47, 95% CI: 1.37, 1.58; recessive model-GG versus TT + TG: OR = 1.37, 95% CI 1.31, 1.43; additive model-2GG + TG versus 2TT + TG: OR = 1.30, 95% CI: 1.25, 1.36). Moreover, increased cancer risk in all genetic models was found after stratification of the SNP data by cancer type, ethnicity and source of controls. CONCLUSIONS: In all genetic models, the association between the TERT rs2736100 polymorphism and cancer risk was significant. This meta-analysis suggests that the TERT rs2736100 polymorphism may be a risk factor for cancer. Further functional studies between this polymorphism and cancer risk are warranted.

Genetic oxidative stress variants and glioma risk in a Chinese population: a hospital-based case-control study.

BACKGROUND: The oxidative stress mechanism is of particular interest in the pathogenesis of glioma, given the high rate of oxygen metabolism in the brain. Potential links between polymorphisms of antioxidant genes and glioma risk are currently unknown. We therefore investigated the association between polymorphisms in antioxidant genes and glioma risk. METHODS: We examined 16 single nucleotide polymorphisms (SNPs) of 9 antioxidant genes (GPX1, CAT, PON1, NQO1, SOD2/MnSOD, SOD3, and NOS1*2*3) in 384 glioma and 384 control cases in a Chinese hospital-based case-control study. Genotypes were determined using the OpenArray platform, which employs the chip-based Taq-Man genotyping technology. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression. RESULTS: Using single-locus analysis, we identified four SNPs (SOD2 V16A, SOD3 T58A, GPX1 -46 C/T, and NOS1 3'-UTR) that were significantly associated with the risk of glioma development. To assess the cumulative effects, we performed a combined unfavourable genotype analysis. Compared with the reference group that exhibited no unfavourable genotypes, the medium- and high-risk groups exhibited a 1.86-fold (95% CI, 1.30-2.67) and a 4.86-fold (95% CI, 1.33-17.71) increased risk of glioma, respectively (P-value for the trend < 0.001). CONCLUSIONS: These data suggest that genetic variations in oxidative stress genes might contribute to the aetiology of glioma.

Application of dural suturing in the endoscopic endonasal approach to the sellar region.

Objectives: The endoscopic endonasal approach (EEA) is widely used in the treatment of cranial base tumors. Skull base reconstruction is a crucial part of EEA, which has a great impact on patients' prognosis. In this study, we report our experience with sellar dural suturing in cranial base reconstruction and retrospectively analyze its effect. Methods: The clinical data of 134 patients who suffered intraoperative CSF leakage and underwent EEA surgery in the Department of Neurosurgery of the First Affiliated Hospital of Nanjing Medical University from October 2018 to November 2020 were retrospectively collected and analyzed. According to whether sellar dural suturing was performed during the operation, they were divided into a suture group (55 cases) and a control group (79 cases). Results: The results showed that dural suturing of the sellar floor effectively reduced the postoperative hospitalization duration (p = 0.026) and the use rates of lumbar drainage (p = 0.047), autologous fat transplantation (p = 0.038), and pedicled nasoseptal flaps (p = 0.026). Conclusion: Sellar dural suturing under endoscopy is a promising and effective method for cranial base reconstruction in EEA surgery and is worthy of clinical application.

[Effect of osteopontin silencing by lentivirus-mediated delivery of siRNA on glioma cell invasion and apoptosis].

OBJECTIVE: To investigate the effect of osteopontin silencing on the invasion and apoptosis of U251 cells. METHODS: The invasion, apoptosis and levels of uPA, MMP-2 and MMP-9 were determined by invasion assay, flow cytometry, Western blot and real-time fluorescence quantitative PCR respectively. RESULTS: Osteopontin small interference RNA (siRNA) inhibited osteopontin expression and cell invasion, promoted apoptosis in U251 cells. In addition, the expression of Bcl-2, uPA, MMP-2 and MMP-9 was decreased, while Bax level was elevated. CONCLUSION: Osteopontin siRNA can inhibit U251 cells invasion via the down-regulation of uPA, MMP-2 and MMP-9 levels, and promote apoptosis through induction of Bax expression and inhibition of Bcl 2 level. It suggests that osteopontin plays an important role in human glioma progression.

[Construction and screening an effective anti-miR-221 RNAi vector in vitro].

OBJECTIVE: To construct and screen an effective anti-miR-221 vector of siRNA. METHODS: Four hairpin structure of siRNA transcript templates targeting miR-221 and a negative control were synthesized, then ligated with pGCSIL-GFP vector and a pEGFP-miR-221 which express pre-miR-221 was also constructed. All the recombinants were sequenced. The confirmed pGCSIL-GFP recombinants by combining with pEGFP-miR-221 were transfected into 293T cells seperately. The expressed Flag protein was detected by Western blot to evaluate the inhibition effect of targeting sequences. Then a recombinant with the highest anti-miR-221 effect was screened and transfected into U87 glioma cell, and its anti-tumor effect was evaluated by MTT and FCM. RESULTS: The resulting recombinants were confirmed by sequencing which demonstrated that the recombinant plasmids contained the correct sequences of designed transcript templates. The results of Western blot indicated the expression of Flag of No 1 recombinant plasmid group was inhibited heavily with a 34.3% expression level by compared with control group. The proliferation inhibition and induced apoptosis by this recombinant with an apoptosis ratio of 21.89% in U87 cell were also observed. CONCLUSION: The anti-miR-221 expression siRNA espression recombinants were constructed successfully, and one sequence with the highest inhibition efficiency was screened out, which could inhibit U87 cell proliferation and induce cell apoptosis, and could be used to suppress target gene for further study in tumor biology.

Glioma cells enhance endothelial progenitor cell angiogenesis via VEGFR-2, not VEGFR-1.

Although potential contribution of endothelial progenitor cells (EPCs) to angiogenesis in glioma has been proposed, the molecular mechanisms of EPCs recruitment to vasculature have not been fully elucidated. Here, we show that the supernatant from glioma cells promotes EPCs angiogenesis via VEGFR-2, not VEGFR-1. Moreover, VEGFR-2 siRNA inhibits VEGFR-2 expression in EPCs, tube formation on matrigel and cell migration. MMP-9 activity and expression and the Akt and ERK phosphorylations are decreased by VEGFR-2 siRNA. Thus, these results indicate that glioma cells enhance EPC angiogenesis via VEGFR-2, not VEGFR-1, mediated by the MMP-9, Akt and ERK signal pathways.

[The construction of lentivirus-mediated RNAi vector containing hTERT].

OBJECTIVE: To construct a recombinant lentivirus RNA interference (RNAi) vector carrying hTERT gene, and to obtain the titer of the lentiviral stock for investigating the expression in the eukaryotic cells and the effect on the hTERT gene silencing in the eukaryotic cells. METHODS: Two complimentary oligos of small interference RNA (siRNA) with hairpin structures targeting the hTERT gene and a negative control were synthesized, then ligated with pLVTHM vector and sequenced. The recombinant vectors were then transfected with viral packaging mix into T293 cells, viral supernatant was harvested to determine the titer. U87 cells infected by virus were harvested and the expression of hTERT, telomerase activity and apoptosis were detected by reverse transcription-PCR(RT-PCR), TRAP assay and flow cytometry separately. RESULTS: Sequencing data showed that the constructed plasmids contained the correct sequences of hTERT siRNA transcript templates. A vector producing cell line T293 was established, and the titer for transfection was obtained. RT-PCR and TRAP flow cytometry analyses demonstrated that hTERT shRNA expression construct could suppress the expression of hTERT and telomerase activity and induce apoptosis. CONCLUSION: A lentivirus RNAi vector targeting hTERT gene was successfully constructed, which decreased the expression of hTERT and telomerase activity effectively and induced apoptosis. It has set up a research platform for the gene therapy of tumors which take hTERT as the target.

Lentiviral vector mediated siRNA knock-down of hTERT results in diminished capacity in invasiveness and in vivo growth of human glioma cells in a telomere length-independent manner.

Glioma cells are characterized by their invasiveness and resistance against conventional therapeutics. Telomerase activity has been suggested to be an important target for glioma treatment. Here we assessed the anticancer effects and its potential mechanisms of lentiviral vector mediated siRNA knock-down of the human telomerase reverse transcriptase (hTERT) in U87MG human glioblastoma cells. Stable expression of anti-hTERT siRNA reduced the hTERT expression and TRAP assay telomerase activity to barely detectable levels. Injection of lentiviral vectors encoding anti-hTERT siRNA significantly inhibited the growth of pre-established macroscopic xenograft tumors, which was in contrast to the finding that no obvious effects on cell growth, cell cycle progression and telomere length were observed in anti-hTERT siRNA expressing U87MG cells during short-term in vitro cultures. The in vivo glioma growth inhibition effect was already evident in the period coincided with no detectable telomere length changes, suggesting that hTERT inhibition may hinder glioma cell growth in a telomere length-independent manner. Importantly, transwell migration assay showed profound inhibitory effect on the invasive capacity of U87MG cells following short-term anti-hTERT siRNA expression. Thus, efficient knock-down of hTERT can inhibit glioma cell proliferation and migration prior to its effect on telomere length.

MicroRNA-625 inhibits the proliferation and increases the chemosensitivity of glioma by directly targeting AKT2.

Glioma is a malignant tumor for which new therapies are needed. Growing evidence has demonstrated that microRNAs (miRNAs) have a major effect on glioma development. Here, we aimed to characterize a novel anti-cancer miRNA, miR-625, by investigating its expression, function, and mechanism of action in glioma progression. The expression of miR-625 and its target mRNA in human glioma tissues and cell lines was assessed by real-time PCR, western blotting, and immunohistochemistry. Functional significance was assessed by examining cell cycle progression, proliferation, apoptosis, and chemosensitivity to temozolomide in vitro, and by examining growth of subcutaneous glioblastoma in a mouse model in vivo. We found that miR-625 expression was significantly lower in human glioma samples and cell lines than in normal brain tissue and human astrocytes. Furthermore, miR-625 overexpression not only suppressed glioma cell proliferation in culture and in the tumor xenograft model but also induced cell cycle arrest and apoptosis. AKT2 was identified as a direct miR-625 target in glioma cell lines, and AKT2 overexpression reversed the suppressive effects of miR-625 in the cell lines and the tumor xenograft model. Finally, we found that the sensitivity of glioma cells to temozolomide was increased by miR-625 overexpression, and this was reversed by concomitant AKT2 expression. In conclusion, our findings suggest that the miR-625-AKT2 axis could be a new prognostic marker and diagnostic target for gliomas.

[Study on combined gene therapy for malignant gliomas transfected with antisense hTERT/PTEN in vitro and in vivo].

OBJECTIVE: To study inhibitory efficacy of combined gene therapy for malignant gliomas transfected with antisense human telomerase reverse transcriptase (hTERT)/PTEN in vitro and in vivo. METHODS: To construct two adenovirus recons which contained antisense hTERT and wild-type PTEN respectively with high performance homologous recombination system in bacteria. The two adenovirus recons were transfected into U251 human malignant glioma cells combinedly or respectively in vitro and in vivo. U251 cell proliferation in vitro was determined by MTT assay and flow cytometry, tumor growth in vivo was measured by the volume of glioma in nude mice. Telomerase activity was detected by telomeric repeat amplification protocol (TRAP) assay. Expression of hTERT and PTEN protein was detected by Western blotting methods. RESULTS: After transfection in vitro, the growth of U251 cells was inhibited significantly. The inhibitory effect was time-dependent. The strongest inhibition was observed in combined transfection group, at the 6th day, the survival rate was 37.6%, telomerase activity (only 28.8TPG) was inhibited significantly, hTERT protein expression was inhibited significantly too, which was 0.2106, but PTEN protein expression was increased significantly, which was 0.9630. In vivo, the growth of tumors was also effectively inhibited. CONCLUSION: Growth of malignant glioma cells is effectively inhibited after transfection with combined antisense hTERT and PTEN in vitro and in vivo.

The effects of ABCC2 G1249A polymorphism on the risk of resistance to antiepileptic drugs: a meta-analysis of the literature.

AIMS: The G1249A variant of the multidrug resistance-associated protein 2 (ABCC2) gene may be associated with the development of antiepileptic drug (AED) resistance. Although numerous studies have investigated the association between the G1249A variant and the risk of drug resistance in epilepsy, the results of these studies have been inconclusive. To assess the role of G1249A polymorphism in drug resistance in epilepsy, a meta-analysis was performed. MATERIALS AND METHODS: We systematically reviewed relevant studies retrieved by the PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on the date extracted from the studies to evaluate the strength of association. We also analyzed the heterogeneity and sensitivity of each report and the publication bias of the studies. RESULTS: A total of 6 published studies, involving 2213 patients (1100 patients with drug-resistant epilepsy and 1113 controls with drug-responsive epilepsy) were reviewed in the present meta-analysis. The overall results indicated that the variant genotypes were associated with a significantly decreased risk of AED resistance (AA vs. GG: OR=0.372, 95% CI=0.182-0.762; recessive model: OR=0.399, 95% CI=0.200-0.795) (fixed-effects model). A stratified analysis by ethnicity showed similar findings for Caucasians in an additive model (A vs. G: OR=0.700, 95% CI=0.494-0.992). CONCLUSIONS: The meta-analysis suggests that the ABCC2 G1249A polymorphism is significantly associated with a decreased risk of AED resistance. However, further functional investigations are warranted to validate the association.

Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection.

Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion.

Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

PURPOSE: CTLA-4 is one of the most fundamental immunosuppressive cotykines which belongs to the immunoglobulin super-family, and is expressed mainly on activated T cells. Previous studies have reported the existence of CTLA4 60G/A and CTLA4 -1661A/G polymorphism in cancers. However, the effects remain conflicting. Hence, we performed a meta-analysis to investigate the association between these polymorphisms and cancer risk. METHODS: We searched the Pubmed and Web of Science databases until October 24, 2013 to obtain relevant published studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between CTLA4 gene polymorphisms and cancer susceptibility were calculated by stata 11 software. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in our meta-analysis. RESULTS: A total of 22 articles comprising 31 case-control studies concerning the CTLA-4 60G/A and CTLA-4 -1661A/G polymorphisms were included in the meta-analysis. The pooled results suggested the CTLA-4 60G/A polymorphism was significantly associated with an increased skin cancer risk (AA vs. GG: OR = 1.32, 95%CI = 1.09-1.59; AA vs. GA+GG: OR = 1.26, 95%CI = 1.07-1.48). For CTLA-4 -1661 A/G polymorphism, the results showed that the CTLA-4 -1661A/G polymorphism was significantly associated with an increased cancer risk (GA vs. AA: OR = 1.44, 95%CI = 1.13-1.82; GA+GG vs. AA: OR = 1.35, 95%CI = 1.07-1.69; G vs. A: OR = 1.21, 95%CI = 1.01-1.47), especially in gastric cancer, breast cancer, other cancers and in Asians population subgroups. CONCLUSION: Our meta-analysis suggests that the CTLA-4 -1661A/G polymorphism is a potential factor for the susceptibility of cancer, especially in gastric cancer, breast cancer and other cancers, and the CTLA-4 60G/A polymorphism is significantly associated with increased skin cancer risk. The effect of the CTLA-4 -1661A/G polymorphism on cancer susceptibility especially exists in Asians and population based subjects.