Transcriptome analysis unveils the mechanisms of lipid metabolism response to grayanotoxin I stress in Spodoptera litura.

Background: Spodoptera litura (tobacco caterpillar, S. litura) is a pest of great economic importance due to being a polyphagous and world-distributed agricultural pest. However, agricultural practices involving chemical pesticides have caused resistance, resurgence, and residue problems, highlighting the need for new, environmentally friendly methods to control the spread of S. litura. Aim: This study aimed to investigate the gut poisoning of grayanotoxin I, an active compound found in Pieris japonica, on S. litura, and to explore the underlying mechanisms of these effects. Methods: S. litura was cultivated in a laboratory setting, and their survival rate, growth and development, and pupation time were recorded after grayanotoxin I treatment. RNA-Seq was utilized to screen for differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to determine the functions of these DEGs. ELISA was employed to analyze the levels of lipase, 3-hydroxyacyl-CoA dehydrogenase (HOAD), and acetyl-CoA carboxylase (ACC). Hematoxylin and Eosin (H & E) staining was used to detect the development of the fat body. Results: Grayanotoxin I treatment significantly suppressed the survival rate, growth and development, and pupation of S. litura. RNA-Seq analysis revealed 285 DEGs after grayanotoxin I exposure, with over 16 genes related to lipid metabolism. These 285 DEGs were enriched in the categories of cuticle development, larvae longevity, fat digestion and absorption. Grayanotoxin I treatment also inhibited the levels of FFA, lipase, and HOAD in the hemolymph of S. litura. Conclusion: The results of this study demonstrated that grayanotoxin I inhibited the growth and development of S. litura. The mechanisms might, at least partly, be related to the interference of lipid synthesis, lipolysis, and fat body development. These findings provide valuable insights into a new, environmentally-friendly plant-derived insecticide, grayanotoxin I, to control the spread of S. litura.

STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma.

STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.

A Novel Putative Role of TNK1 in Atherosclerotic Inflammation Implicating the Tyk2/STAT1 Pathway.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease which is responsible for many clinical manifestations. The present study was to investigate the anti-inflammatory functions and mechanisms of TNK1 in atherosclerosis. METHODS: The ApoE(-/-) mice and human carotid endarterectomy (CEA) atherosclerotic plaques were used to investigate the differential expression of TNK1. The ApoE(-/-) mice were fed with high-fat diet (HFD) or normal-fat diet (NFD) for 8 weeks; the aorta was separated and stained with oil red O to evaluate the formation of atherosclerosis. TNK1 in mice aorta was measured by qPCR. The human CEA were obtained and identified as ruptured and stable plaques. The level of TNK1 was measured by qPCR and Western-blot staining. Further studies were conducted in THP-1 cells to explore the anti-inflammatory effects of TNK1. We induced the formation of macrophages by incubating THP-1 cells with PMA (phorbol 12-myristate 13-acetate). Afterwards, oxidized low-density lipoprotein (oxLDL) was used to stimulate the inflammation, and the secretion of inflammatory factors was measured by ELISA and qPCR. The levels of TNK1, total STAT1 and Tyk2, and the phosphorylation of STAT1 and Tyk2 were measured by western blot to uncover the mechanisms of TNK1. RESULTS: The oil red O staining indicated obvious deposition of lipid on the aorta of ApoE(-/-) mice after 8-week HFD treatment. The TNK1 level was much higher in both the HFD-fed ApoE(-/-) mice aorta arch and the ruptured human CEA plaques. We found that TNK1 was highly expressed in THP-1 cells, compared to other atherosclerotic related cells (HUVEC, HBMEC, and HA-VSMC), indicating TNK1 might be involved in the inflammation. Suppressing the expression of TNK1 by shTNK1 inhibited the oxLDL-induced secretion of inflammatory factors, such as IL-12, IL-6, and TNF-α. ShTNK1 also inhibited the uptake of lipid and decreased the cellular cholesterol content in THP-1 cells. Furthermore, the shTNK1 suppressed the oxLDL-induced phosphorylation of Tyk2 and STAT1. CONCLUSION: TNK1 participated in the inflammation in atherosclerosis. shTNK1 suppressed the oxLDL-induced inflammation and lipid deposition in THP-1 cells. The mechanism might be related to the Tyk2/STAT signal pathway.

The Association between MUC5B Rs35705950 and Risks of Idiopathic Interstitial Pneumonia, Systemic Sclerosis Interstitial Lung Disease, and Familial Interstitial Pneumonia: A Meta-Analysis.

BACKGROUND: Interstitial lung disease (ILD) is a category of chronic lung diseases with more than 200 subtypes. Idiopathic interstitial pneumonia (IIP), systemic sclerosis (SSc) ILD, and familial interstitial pneumonia (FIP) are three major groups of lung diseases with different causes or with unknown causes. Mucin5B (MUC5B) belongs to the mucin family, which contribute to the lubricating and viscoelastic properties of the whole saliva, normal lung mucus, and cervical mucus. The association between MUC5B rs35705950 and ILDs risks has been widely studied. However, the results were inconclusive and inconsistent. METHODS: In the present meta-analysis, the database PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI and Chinese Biomedical Literature Database were searched till Aug 20th, 2018. Overall 16 publications with 28 studies, 76345 cases and 18402 controls were included. RESULTS: The results indicated a significant increase of overall IIP risk for TT genotype and T allele of the rs35705950 in all genetic models (TT vs GG, OR=9.11; TT vs GT+TT, OR=5.80; GT+TT vs GG, OR=4.34; T vs G, OR=4.03. P<0.0001). Subgroup analysis by subtypes of IIP revealed higher risks of TT genotype and T allele for IPF and iNSIP (P<0.05). A significant increase of FIP risk was also found for the TT genotype and T allele of the rs35705950 (TT vs GG, OR=17.08; GT+TT vs GG, OR=6.02; T vs G, OR=1.64.P<0.05). CONCLUSION: No significant relations existed between the rs35705950 and SSc-ILD risks. MUC5B rs35705950 might be a predictor for the susceptibility of IIP and FIP.

Dual energy computed tomography for detection of metastatic lymph nodes in patients with hepatocellular carcinoma.

BACKGROUND: Regional lymph node metastasis in patients with hepatocellular carcinoma (HCC) is not uncommon, and is often under- or misdiagnosed. Regional lymph node metastasis is associated with a negative prognosis in patients with HCC, and surgical resection of lymph node metastasis is considered feasible and efficacious in improving the survival and prognosis. It is critical to characterize lymph node preoperatively. There is currently no consensus regarding the optimal method for the assessment of regional lymph nodes in patients with HCC. AIM: To evaluate the diagnostic value of single source dual energy computed tomography (CT) in regional lymph node assessment for HCC patients. METHODS: Forty-three patients with pathologically confirmed HCC who underwent partial hepatectomy with lymphadenectomy were retrospectively enrolled. All patients underwent dual-energy CT preoperatively. Regional lymph nodes (n = 156) were divided into either a metastatic (group P, n = 52) or a non-metastasis group (group N, n = 104), and further, according to pathology, divided into an active hepatitis (group P1, n = 34; group N1, n = 73) and a non-active hepatitis group (group P2, n = 18; group N2, n = 31). The maximal short axis diameter (MSAD), iodine concentration (IC), normalized IC (NIC), and the slope of the spectral curve (λ HU) of each group in the arterial phase (AP), portal phase (PP), and delayed phase (DP) were analyzed. RESULTS: Analysis of the MSAD, IC, NIC, and λ HU showed statistical differences between groups P and N (P < 0.05) during all three phases. To distinguish benign from metastatic lymph nodes, the diagnostic efficacy of IC, NIC, and λ HU in the PP was the best among the three phases (AP, PP, and DP), with a sensitivity up to 81.9%, 83.9%, and 81.8%, and a specificity up to 82.4%, 84.1% and 84.1%, respectively. The diagnostic value of combined analyses of MSAD with IC, NIC, or λ HU in the PP was superior to the dual energy CT parameters alone, with a sensitivity up to 84.5%, 86.9%, and 86.2%, and a specificity up to 83.0%, 93.6% and 89.8%, respectively. Between groups P1 and P2 and groups N1 and N2, only IC, NIC, and λ HU between groups N1 and N2 in the PP had a statistically significant difference (P < 0.05). CONCLUSION: Dual-energy CT contributes beneficially to regional lymph node assessment in HCC patients. Combination of MSAD with IC, NIC, or λ HU values in the PP is superior to using any single parameter alone. Active hepatitis does not deteriorate the capabilities for characterization of metastatic lymph nodes.

An improved least squares SVM with adaptive PSO for the prediction of coal spontaneous combustion.

The problem of coal spontaneous combustion prediction is very complex, and there are many factors that affect the prediction results. In order to solve the issues of high dimension and redundancy among features and limited samples in the prediction of coal spontaneous combustion, this paper proposes a prediction algorithm of coal spontaneous combustion based on least squares support vector machine and adaptive particle swarm optimization (APSO-LSSVM). The adaptive PSO algorithm is used to solve the problems such as high computational complexity and slow calculation speed of the LS-SVM model for large-scale samples, so that it can always obtain the optimal solution, and its training speed and accuracy are improved. This method adjusts the inertia weight based on the convergence degree of group and the adaptive value of an individual for accelerating the training speed of swarm. After that, the improved PSO is used to iteratively solve the matrix equations in LS-SVM. APSO-LSSVM avoids the matrix inversion, saves the internal memory and obtains the optimum solution. The experiment results show that this method simplifies the training sample, accelerates the training speed, and also offers superior classification accuracy, fast convergence speed and good generalization ability.

Feature extraction of face image based on LBP and 2-D Gabor wavelet transform.

Affected by illumination, gesture, expression and other factor's variation, face image pattern is easy to be changed, so it is important to find a robust data representation for the correct classification of face pattern. In this paper, a face image recognition algorithm based on 2-D Gabor wavelet transform and Local Binary Pattern (LBP) is proposed. LBP is a local describe operator, which is invariant against illumination variation. 2-D Gabor wavelet transform have the invariant property against pose and expression variation. Experimental results show that the large scale 2-D Gabor wavelet representation could get good classification accuracy. Using LBP to describe 2-D Gabor wavelet representation of face image, together with image block, histogram statistics, PCA dimensionality reduction, nearestneighbors classification, we finally find this algorithm can get a better classification performance in different scales and directions.

Expression of CCL21 by EBV-associated gastric carcinoma cells protects CD8+CCR7+ T lymphocytes from apoptosis via the mitochondria-mediated pathway.

About 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV), which are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are usually accompanied by massive lymphocytes infiltration, among which CD8+ T cells are predominant. To date, the apoptosis of the infiltrating CD8+ T cells in EBVaGC has not been investigated. In the present study, we assessed the immunophenotype and apoptosis of tumour infiltrating lymphocytes (TILs) in both EBVaGC and EBV-negative gastric carcinoma (EBVnGC). We found that CD8+CCR7+ T lymphocytes were increased in EBVaGC compared to EBVnGC [60.53 ± 28.41/high power fields (HPF) vs 19.63 ± 15.97/HPF; p < 0.001]. Moreover, the apoptosis index of TILs was lower in EBVaGC than that in EBVnGC (1.34 ± 0.90 vs 5.94 ± 3.77; p < 0.001). Given that the CCL21-CCR7 axis is reported to be potentially involved in apoptosis, we examined the expression of CCL21 in both EBVaGC and EBVnGC. We found that CCL21 expression was higher in EBVaGC than in EBVnGC (p < 0.001). We also showed that the expression of CCL21 by EBVaGC cells protected CD8+CCR7+ T lymphocytes from apoptosis. Furthermore, the up-regulation of Bcl-2 contributed to the inhibition of apoptosis in CD8+CCR7+ T cells. Collectively, these findings suggest that expression of CCL21 by EBVaGC cells protects CD8+CCR7+ T lymphocytes from apoptosis via the mitochondria-mediated pathway. To our best knowledge, this is the first study to investigate the apoptosis of CD8+ T cells in EBVaGC.

AGBL2 promotes cancer cell growth through IRGM-regulated autophagy and enhanced Aurora A activity in hepatocellular carcinoma.

AGBL2 has been reported to catalyze α-tubulin detyrosination, by which it promotes tumorigenesis and cancer progression. However, its potential role in the pathogenesis of hepatocellular carcinoma (HCC) has not been revealed yet. In the present study, AGBL2 was frequently found being overexpressed in HCC tissues and cell lines. In a large cohort of clinical HCC tissues, high expression of AGBL2 was positively associated with tumor size, tumor multiplicity and advanced clinical stage (p < 0.05), and it was an independent prognostic factor for HCC patients. In HCC cell lines, ectopic overexpression of AGBL2 substantially enhanced HCC cells survival and proliferation in vitro and promoted tumor growth in vivo. In addition, we demonstrated that overexpression of AGBL2 in HCC cells notably inhibited apoptosis by enhancing IRGM-regulated autophagy. Meanwhile, AGBL2 could up-regulate the expression of TPX2 and Aurora A activity to promote cell proliferation in HCC cells. In summary, our findings suggest that up-regulation of AGBL2 plays a critical oncogenic role in the pathogenesis of HCC through modulation on autophagy and Aurora A activity, and it could be a candidate for prognostic marker and therapeutic target in HCC.

Effect of bosentan is correlated with MMP-9/TIMP-1 ratio in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis (PF) is a life-threatening non-tumorous disease characterized by progressive fibrosis and worsening lung function. Various drugs, such as bleomycin, can contribute to lung injury and PF, with lung injury potentially occurring in 10% of bleomycin users. Bleomycin is the most commonly used drug in the establishment of an animal model of PF in rats. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) serve an important role in controlling tissue organization and fibrosis following injury. The present study examined the effect of bosentan on fibrotic lung tissue in rats administrated with bleomycin. In total, 48 Wistar rats were administrated with bleomycin, with or without bosentan, while the control rats received saline. The lung tissues were microscopically examined by staining with hematoxylin and eosin and Masson's trichome. ELISA was also used to detect the MMP-9 and TIMP-1 concentrations in the plasma. The results indicated that the bosentan-treated groups on the next day and the 15th day showed significant reversal of pathological findings. In addition, the concentrations of MMP-9 and TIMP-1 appeared to be altered following bosentan treatment, improving the bleomycin-induced PF. Masson's trichome staining showed high collagen deposition in the lung tissue sections, which may be a direct result of the activity of MMP-9 and TIMP-1. Furthermore, the deposition of collagen was significantly inhibited in bosentan-treated groups. In conclusion, these results demonstrated that bosentan inhibited lung fibrosis induced by bleomycin and it may be used as an inhibitor of PF.

Clinical significance of spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia in Epstein-Barr virus-associated and Epstein-Barr virus-negative gastric cancer.

Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM) have been recognized as neoplastic precursors in gastric carcinogenesis. We explored the relationship between SPEM and IM in Epstein-Barr virus-associated (EBVaGC) and Epstein-Barr virus-negative (EBVnGC) gastric cancer. Sixty-four EBVaGC and one hundred and fifty-four EBVnGC patients were included. EBV positivity was identified using Epstein-Barr virus-encoded RNA-1 in situ hybridization. SPEM was subclassified into absent, early, and advanced SPEM. Acute and chronic inflammation was graded as absent, mild, moderate, and marked. Univariate and multivariate logistic regression analyses were conducted to analyze the correlation between SPEM, IM, and inflammation. Our study revealed that SPEM was detected in 87.5% EBVaGC and 85.1% EBVnGC patients. Distribution of patients according to the SPEM classification was significantly different between EBVaGC and EBVnGC groups (P=.038). IM was observed less frequently in EBVaGC when compared with EBVnGC patients (P<.001). No difference was observed between EBVaGC and EBVnGC in the levels of acute and chronic inflammation. A positive correlation between IM and SPEM status was observed in both EBVaGC and EBVnGC patients. Furthermore, advanced SPEM was an independent influential factor to IM in EBVnGC (P=.013). In conclusion, SPEM was associated with both EBVaGC and EBVnGC more frequently than IM. Moreover, advanced SPEM had a stronger association with IM than early SPEM in EBVnGC. These results suggest that identification of SPEM should be used as a high-risk indicator for detecting early gastric carcinoma, and should be brought to the attention of pathologists and clinicians.

Rhubarb attenuates blood-brain barrier disruption via increased zonula occludens-1 expression in a rat model of intracerebral hemorrhage.

Blood-brain barrier (BBB) disruption is a key pathophysiological factor of intracerebral hemorrhage (ICH). The level of zonula occludens-1 (ZO-1) has been closely associated with the degree of BBB damage, and is an indicator of BBB destruction. The aim of the present study was to evaluate the effects of rhubarb on BBB function in a rat model of ICH. ICH was induced in rats by treatment with type VII collagenase. Sham-operated rats were administered with an equal volume of saline. Following the administration of rhubarb decoction (20 g/kg), neurobehavioral function evaluation and Evans blue extravasation assays were performed at days 1, 3 and 5 after ICH. ZO-1 expression in the brain of ICH-induced rats were analyzed via reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses. The results suggested that rhubarb significantly ameliorated neurological symptoms and attenuated BBB permeability. The results of immunohistochemistry and RT-PCR studies indicated that the expression of ZO-1 expression was robust in the sham-operated group and was weak in the vehicle-treated group at day 3. The present data indicated that rhubarb effectively attenuated ICH-induced BBB damage in rats, raising the possibility that rhubarb or its active components may be considered useful as neuroprotective drugs for ICH. The protective mechanisms appeared to involve the preservation of BBB integrity and elevation of ZO-1 protein expression levels.

A new prognostic histopathologic classification of nasopharyngeal carcinoma.

BACKGROUND: The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response. METHODS: We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). RESULTS: The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P < 0.001). In multivariate models, patients with MSEC had a shorter OS than patients with EC (HR = 1.44, 95% CI = 1.27-1.62), SC (HR = 2.00, 95% CI = 1.76-2.28), or SCC (HR = 4.23, 95% CI = 3.34-5.38). Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC (HR = 0.67, 95% CI = 0.56-0.80), MSEC (HR = 0.58, 95% CI = 0.49-0.75), and possibly for those with SCC (HR = 0.63; 95% CI = 0.40-0.98), but not for patients with SC (HR = 0.97, 95% CI = 0.74-1.28). CONCLUSIONS: The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associated with a poor prognosis.

Expression and prognostic roles of PIK3CA, JAK2, PD-L1, and PD-L2 in Epstein-Barr virus-associated gastric carcinoma.

As a special subtype of gastric carcinoma, Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. The Cancer Genome Atlas Research Network revealed that EBVaGC also has distinct molecular features: PIK3CA mutations, DNA hypermethylation, and JAK2, PD-L1, and PD-L2 amplification. Here, we evaluated PIK3CA, JAK2, PD-L1, and PD-L2 expression in 59 EBVaGC and 796 EBV-negative gastric carcinoma (EBVnGC) cases using immunohistochemistry and found that PIK3CA, JAK2, PD-L1, and PD-L2 were highly expressed in 75.9% and 48.8% (P<.001), 81.8% and 71.1% (P=.091), 92.5% and 84.8% (P=.132), and 98.1% and 89.7% (P=.049) of the EBVaGC and EBVnGC cases, respectively. However, the expression of PIK3CA, JAK2, PD-L1, or PD-L2 was not significantly associated with clinicopathological features or patient outcomes in EBVaGC. In contrast, in EBVnGC, high PIK3CA expression was significantly associated with indolent clinicopathological features and independently predicted better 5-year overall survival (57.8% versus 33.4%, P<.001). Our study indicated that the protein expression of the 4 characteristic molecules of EBVaGC was basically consistent with their genetic alterations, making them potential characteristic protein biomarkers and therapeutic targets of EBVaGC. The favorable impact of PIK3CA overexpression on survival found in this study gives us new insight into the clinical significance of PIK3CA in EBVnGC.

CPEB4 interacts with Vimentin and involves in progressive features and poor prognosis of patients with astrocytic tumors.

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, it is unclear whether CPEB4 has any clinical significance in patients with astrocytic tumors, and mechanisms that CPEB4 contribute to progression of astrocytic tumors remain largely unknown. Here, correlation between CPEB4 expression and prognosis of patients with astrocytic tumors were explored by using qPCR, WB and IHC, and X-tile, SPSS software. Cell lines U251 MG and A172 were used to study CPEB4's function and mechanisms. Co-immunoprecipitation, mass spectrometry, immunofluorescent assay, and western blot were performed to observe the interaction between CPEB4 and Vimentin. CPEB4 mRNA and protein levels were markedly elevated in 12/12 astrocytic tumors in comparison to paratumor. High expression of CPEB4 was significantly correlated with clinical progressive futures and work as an independent adverse prognostic factor for overall survival of patients with astrocytic tumors (relative risk 4.5, 95 % CI 2.1-11.2, p = 0.001). Moreover, knockdown of CPEB4 in astrocytic tumor cells inhibited their proliferation ability , clonogenicity, and invasiveness. Five candidate proteins, GRP78, Mortalin, Keratin, Vimentin, and ß-actin, were identified, and the interaction between CPEB4 and Vimentin was finally confirmed. Downregulation of CPEB4 could reduce the protein expression of Vimentin. Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors.

MRI findings in primary vaginal melanoma-a report of four cases.

Primary vaginal melanoma is a rare malignant tumor. We review the clinical presentation and magnetic resonance imaging (MRI) appearances of this entity in four patients. The MRI findings in vaginal melanoma are various and may be confused with other malignant vaginal tumor. Pelvic MRI is helpful for accurate preoperative staging of vaginal melanoma.

Downregulation of MACC1 inhibits invasion, migration and proliferation, attenuates cisplatin resistance and induces apoptosis in tongue squamous cell carcinoma.

The aim of the present study was to investigate the expression and function of metastasis-associated in colon cancer 1 (MACC1) in tongue squamous cell carcinoma (TSCC) and its relationship with the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147). Levels of MACC1 and EMMPRIN expression were analyzed in 65 paraffin­embedded tissue specimens of TSCC and in the adjacent non-cancerous tissues using immunohistochemistry (IHC). MACC1 expression was highly associated with lymphatic metastasis and EMMPRIN expression. Overexpression of MACC1 was significantly correlated with poor overall patient survival. A small interfering RNA (siRNA) was delivered into TSCCA cells to downregulate MACC1 expression. The CCK-8 assay showed that TSCCA cell proliferation was markedly reduced and that cisplatin resistance was attenuated. The suppression of MACC1 promoted the apoptosis of the TSCCA cell line. A Transwell experiment demonstrated that the migration and invasion abilities of the TSCCA cells were extremely downregulated. An ELISA experiment and western blotting revealed that the secretion of urokinase-type plasminogen activator system (uPA) in the supernatant of the culture medium and uPA expression were significantly reduced. Experiments revealed that the secretion of metalloproteinase 2 (MMP2) in the supernatant of the culture medium and MMP2 expression were not affected. MACC1 may serve as a novel biomarker and therapeutic target for TSCC.