Insecticidal activity, Chemical Constituents of Trachyspermum ammi, Withania coagulans and Murraya koenigii ethanloic extracts against Bemisia tabaci / Atividade inseticida, constituintes químicos de extratos etanloicos de Trachyspermum ammi, Withania coagulans e Murraya koenigii contra Bemisia tabaci

Whitefly is one of the most widespread agricultural pests in the world. Essential oils might be used to control this insect in an environmentally responsible way. The fumigant, repellent, and anti-oviposition activity of ethanol-extracted essential oils of Trachyspermum ammi, Withania coagulans, and Murraya koenigii against Bemisia tabaci was investigated in this study. In the experiment, three essential oil concentrations (2.5 mg/mL, 5 mg/mL, and 10 mg/mL) were used. Trachyspermum ammi had the highest percentage of whitefly death in laboratory experiments due to its fumigant toxicity; the same tendency was found in contact toxicity and repellent effect. Mortality percent rises as the concentration of essential oil increases with bioassay time. As the concentration of essential oil grows with bioassay time, so does the mortality rate. The most adult whiteflies escaped from the treated plants' greenhouse due to the highest essential oil concentration. The greatest repellency was found with Trachyspermum ammi essential oil at 10 mg/mL. The essential oil had the greatest anti-oviposition efficacy against whiteflies. Trachyspermum ammi possessed the most potent anti-oviposition deterrent, followed by Withania coagulans in second place. Murraya koenigii finished third with moderate anti-oviposition, which affects the number of eggs produced in comparison to the control. As a consequence, these three oils might be used as an effective and environmentally acceptable bio-insecticide to control B. tabaci.

A mosca-branca é uma das pragas agrícolas mais difundidas no mundo. Os óleos essenciais podem ser usados ​​para controlar esse inseto de forma ambientalmente responsável. A atividade fumigante, repelente e antioviposição de óleos essenciais extraídos com etanol de Trachyspermum ammi, Withania coagulans e Murraya koenigii contra Bemisia tabaci foi investigada neste estudo. No experimento, foram utilizadas três concentrações de óleo essencial (2,5 mg/mL, 5 mg/mL e 10 mg/mL). Trachyspermum ammi teve a maior porcentagem de morte de mosca-branca em experimentos de laboratório devido à sua toxicidade fumigante; a mesma tendência foi encontrada na toxicidade de contato e efeito repelente. A porcentagem de mortalidade aumenta à medida que a concentração de óleo essencial aumenta com o tempo do bioensaio. À medida que a concentração de óleo essencial cresce com o tempo de bioensaio, o mesmo acontece com a taxa de mortalidade. A maioria das moscas-brancas adultas escapou da estufa das plantas tratadas devido à maior concentração de óleo essencial. A maior repelência foi encontrada com óleo essencial de Trachyspermum ammi a 10 mg/mL. O óleo essencial apresentou a maior eficácia antioviposição contra moscas-brancas. Trachyspermum ammi teve o mais potente impedimento antioviposição, seguido por Withania coagulans em segundo lugar. Murraya koenigii terminou em terceiro com antioviposição moderada, o que afeta o número de ovos produzidos em relação ao controle. Como consequência, esses três óleos podem ser usados ​​como um bioinseticida eficaz e ambientalmente aceitável para controlar B. tabaci.

Insecticidal activity, Chemical Constituents of Trachyspermum ammi, Withania coagulans and Murraya koenigii ethanloic extracts against Bemisia tabaci.

Whitefly is one of the most widespread agricultural pests in the world. Essential oils might be used to control this insect in an environmentally responsible way. The fumigant, repellent, and anti-oviposition activity of ethanol-extracted essential oils of Trachyspermum ammi, Withania coagulans, and Murraya koenigii against Bemisia tabaci was investigated in this study. In the experiment, three essential oil concentrations (2.5 mg/mL, 5 mg/mL, and 10 mg/mL) were used. Trachyspermum ammi had the highest percentage of whitefly death in laboratory experiments due to its fumigant toxicity; the same tendency was found in contact toxicity and repellent effect. Mortality percent rises as the concentration of essential oil increases with bioassay time. As the concentration of essential oil grows with bioassay time, so does the mortality rate. The most adult whiteflies escaped from the treated plants' greenhouse due to the highest essential oil concentration. The greatest repellency was found with Trachyspermum ammi essential oil at 10 mg/mL. The essential oil had the greatest anti-oviposition efficacy against whiteflies. Trachyspermum ammi possessed the most potent anti-oviposition deterrent, followed by Withania coagulans in second place. Murraya koenigii finished third with moderate anti-oviposition, which affects the number of eggs produced in comparison to the control. As a consequence, these three oils might be used as an effective and environmentally acceptable bio-insecticide to control B. tabaci.

MicroRNA-802 promotes the progression of osteosarcoma through targeting p27 and activating PI3K/AKT pathway.

PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

A novel 12-gene signature as independent prognostic model in stage IA and IB lung squamous cell carcinoma patients.

BACKGROUND: There is currently no formal consensus on the administration of adjuvant chemotherapy to stage I lung squamous cell carcinoma (LUSC) patients despite the poor prognosis. The side effects of adjuvant chemotherapy need to be balanced against the risk of tumour recurrence. Prognostic markers are thus needed to identify those at higher risks and recommend individualised treatment regimens. METHODS: Clinical and sequencing data of stage I patients were retrieved from the Lung Squamous Cell Carcinoma project of the Cancer Genome Atlas (TCGA) and three tissue microarray datasets. In a novel K-resample gene selection algorithm, gene-wise Cox proportional hazard regressions were repeated for 50 iterations with random resamples from the TCGA training dataset. The top 200 genes with the best predictive power for survival were chosen to undergo an L1-penalised Cox regression for further gene selection. RESULTS: A total of 602 samples of LUSC were included, of which 42.2% came from female patients, 45.3% were stage IA cancer. From an initial pool of 11,212 genes in the TCGA training dataset, a final set of 12 genes were selected to construct the multivariate Cox prognostic model. Among the 12 selected genes, 5 genes, STAU1, ADGRF1, ATF7IP2, MALL and KRT23, were adverse prognostic factors for patients, while seven genes, NDUFB1, CNPY2, ZNF394, PIN4, FZD8, NBPF26 and EPYC, were positive prognostic factors. An equation for risk score was thus constructed from the final multivariate Cox model. The model performance was tested in the sequestered TCGA testing dataset and validated in external tissue microarray datasets (GSE4573, GSE31210 and GSE50081), demonstrating its efficacy in stratifying patients into high- and low-risk groups with significant survival difference both in the whole set (including stage IA and IB) and in the stage IA only subgroup of each set. The prognostic power remains significant after adjusting for standard clinical factors. When benchmarked against other prominent gene-signature based prognostic models, the model outperformed the rest in the TCGA testing dataset and in predicting long-term risk at eight years in all three validation datasets. CONCLUSION: The 12-gene prognostic model may serve as a useful complementary clinical risk-stratification tool for stage I and especially stage IA lung squamous cell carcinoma patients to guide clinical decision making.

Mutations in chronic myelomonocytic leukemia and their prognostic relevance.

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy that overlaps with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and tends to transform into acute myeloid leukemia (AML). Among cases of CMML, > 90% have gene mutations, primarily involving TET2 (~ 60%), ASXL1 (~ 40%), SRSF2 (~ 50%), and the RAS pathways (~ 30%). These gene mutations are associated with both the clinical phenotypes and the prognosis of CMML, special CMML variants and pre-phases of CMML. Cytogenetic abnormalities and the size of genome are also associated with prognosis. Meanwhile, cases with ASXL1, DNMT3A, NRAS, SETBP1, CBL and RUNX1 mutations may have inferior prognoses, but only ASXL1 mutations were confirmed to be independent predictors of the patient outcome and were included in three prognostic models. Novel treatment targets related to the various gene mutations are emerging. Therefore, this review provides new insights to explore the correlations among gene mutations, clinical phenotypes, prognosis, and novel drugs in CMML.

A two-in-one Janus NIR-II AIEgen with balanced absorption and emission for image-guided precision surgery.

Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.

Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor.

BACKGROUND: Identifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains significant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy. METHODS: 137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita's overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples. RESULTS: Among all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy. In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.14-13.48; P = 0.030) and a longer progression-free survival (PFS) (median: 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.16-3.79; P = 0.014) and overall survival (OS) (median: NA vs. 8.97 months; HR 3.53; 95% CI 1.49-8.38; P = 0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43 months vs. 1.84 months; HR 13.98; 95% CI 4.37-44.68; P < 0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.22-7.03; P = 0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratification in a pooled cohort. CONCLUSION: The circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers.

MicroRNA-596 is epigenetically inactivated and suppresses prostatic cancer cell growth and migration via regulating Wnt/ß-catenin signaling.

OBJECTIVES: Although studies have reported that miR-596 extensively participates in multiple cancer progression, the biological mechanisms and effects of miR-596 in prostatic cancer remain unclear. The literature is aimed to reveal the function and possible molecular mechanisms of miR-596 in prostatic cancer carcinogenesis. MATERIALS AND METHODS: qRT-PCR was applied to examine miR-596 expression in prostatic cancer cell lines and samples, also methylation-specific PCR was used to detect the methylation status of the promoter CpG islands in prostatic cancer samples. Meanwhile, the tumor-related effects of miR-596 were detected via cell viability, clone formation assay, migration assay, flow cytometric and AO/EB assay. qRT-PCR and Western blots were applied to investigate the function of miR-596 on malignant behavior in prostatic cancer cells. RESULTS: We found that miR-596 mRNA was decreased in prostatic cancer samples and cell lines. miR-596 mRNA level was also correlated to cancer stage, Gleason scores, while miR-596 promoter methylation was related to cancer tumor stage, Gleason score and preoperative PSA levels. miR-596 inhibited the cell growth and activity by causing cell apoptosis, and also suppressed the migration of prostatic cancer cells by revealing the epithelial-mesenchymal transition process. In addition, Western blot indicates that miR-596 overexpression deregulated Wnt/ß-catenin signaling, by restraining phosphorylation levels of ß-catenin and expression levels of downstream targets. CONCLUSIONS: In summary, this research indicates that miR-596 overexpression could be potentially useful in the cell growth and migration of prostatic cancer and serves as a potential molecular marker in prostatic cancer.

Downregulation of HOXA11 enhances endometrial cancer malignancy and cisplatin resistance via activating PTEN/AKT signaling pathway.

PURPOSE: Endometrial cancer is the most common malignant tumor of female genital system worldwide. Homeobox A11 (HOXA11) is an evolutionarily conserved Homeobox gene closely implicated in carcinogenesis. However, the mechanisms of HOXA11 in the progression and cisplatin resistance of endometrial cancer remain unclear. METHODS: The expression of HOXA11 was analyzed based on 548 endometrial cancer and 35 control tissues from The Cancer Genome Atlas (TCGA) database. Transwell assay was performed to investigate the effect of HOXA11 on endometrial cell migration and invasion. TUNEL staining was carried out to assay the role of HOXA11 in endometrial cell apoptosis. Western blot was employed to detect the protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), cleaved caspase-3, matrix metalloproteinase-2/9 (MMP/9), phosphatase and tensin homolog (PTEN), protein kinase B (AKT) and p-AKT. RESULTS: TCGA data showed that HOXA11 expression was significantly down-regulated in endometrial cancer tissue samples. The overexpression of HOXA11 promoted the apoptosis, but inhibited the proliferation, migration and invasion of endometrial cancer cells. HOXA11 knockdown with small interfering RNA (siRNA) considerably repressed cell apoptosis, while promoted cell proliferation, migration, and invasion through PTEN/AKT signaling pathway. Interestingly, HOXA11 was lowly expressed in Ishikawa cells treated with cisplatin. In addition, HOXA11 knockdown increased the resistance of endometrial cancer to cisplatin through activating PTEN/AKT signaling pathway. CONCLUSION: Low HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells, and increase their resistance to cisplatin through activating PTEN/AKT pathway.

Identification of a novel immune prognostic model in gastric cancer.

PURPOSE: The tumor immune microenvironment (TIME) is now considered as an important factor during gastric cancer (GC) development. This study identified a novel immune-related risk model for predicting prognosis and assessing the immune status of GC patients. METHODS: Transcriptomic data were obtained from the TCGA database. The differential expressed immune-related genes (IRGs) were identified through the ImmPort portal. Enrichment analysis was performed to explore the potential molecular mechanism of these IRGs. By the Cox regression analysis, we constructed the immune prognostic model. Then, the association between the model and the immune microenvironment was estimated. The model was validated in the GSE84433 dataset. RESULTS: Totally, we identified 222 differentially expressed IRGs. These IRGs were closely correlated with immune response and immune signaling pathways. Through the Cox regression analysis, we developed the immune prognostic model based on the expression of seven IRGs (CXCL3, NOX4, PROC, FAM19A4, RNASE2, IGHD2-15, CGB5). Patients were stratified into two groups according to immune-related risk scores. Survival analysis indicated that the prognosis of high-risk patients was poorer than low-risk patients. Moreover, the immune-related risk score was an independent prognostic biomarker. More importantly, we found that the infiltration level of immunosuppressive cells and the expression of inhibitory immune checkpoints were higher in high-risk patients. The immune microenvironment tended to be a suppressive status in patients with high-risk scores. CONCLUSION: This study demonstrated that our model had predictive value for prognosis and the TIME in GC. It might be a robust tool to improve personalized patient management.

Computed tomography reconstruction for evaluating response in axillary lymph nodes of breast cancer after neoadjuvant chemotherapy.

PURPOSE: To assess the performance of computed tomography (CT) reconstruction in evaluating the response in metastatic lymph nodes after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Patients undergoing pre-NAC and post-NAC CT were identified from the Peking University Cancer Hospital database. Axillary Lymph nodes (ALNs) that shrunk to < 5 mm in short-axis diameter after NAC on CT reconstruction images were classified as clinical complete response. Evaluations of CT reconstruction on ALNs were correlated with residual nodal disease in the final pathology. Overall, 53 invasive breast cancer patients between October 2016 and March 2018 were eligible for our study. The median age was 48 (range 35-70) years. Most women presented with T2 tumors (35/53, 66.0%). RESULTS: After NAC, 20 (37.7%) patients without residual nodal disease were defined as pCR. Of 53 patients, 18 (33.9%) showed negative conversion of ALNs on CT reconstruction evaluation; axillary pCR was present in 16/18 (88.9%) patients. Among 35 patients with abnormal nodes on post-NAC CT reconstruction, 31 (88.6%) had axillary metastasis on the final pathology. The sensitivity and specificity of CT reconstruction in predicting node-negative status were 80.0% and 93.9%, respectively. The positive predictive value was 84.9% for lymph node pCR. The area under the receiver operating characteristic curve of each imaging modality was 0.870 (95% confidence interval 0.755-0.984). CONCLUSIONS: CT reconstruction was useful for evaluating ALNs response following NAC and may be used to predict axillary nodes' pCR with adequate accuracy.

Serum CXCL13 and PECAM-1 can be used as diagnostic and prognostic markers in elderly patients with gastric cancer.

PURPOSE: To investigate the application value of serum CXC Chemokine-13 (CXCL-13) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in elderly patients with gastric cancer (GC). METHODS: Ninety-eight elderly GC patients admitted to the Affiliated Hexian Memorial Hospital of Southern Medical University were selected as a research group, and 60 healthy subjects of the same age and in relatively good health who underwent physical examination at the same period were selected as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of CXCL13 and PECAM-1 in serum. The clinical diagnosis and prognostic value of serum CXCL13 and PECAM-1 in elderly GC patients were analyzed. RESULTS: The levels of CXCL13 and PECAM-1 in serum of the research group were significantly higher than those of the control group (P < 0.001). The AUC value of combined diagnosis of elderly GC patients by serum CXCL13 and PECAM-1 was 0.950, and that of combined evaluation of prognosis of patients was 0.849. Serum CXCL13 and PECAM-1 were significantly related to TNM staging, differentiation degree and tumor diameter in elderly GC patients (P < 0.05). High levels of CXCL13 and PECAM-1 were significantly associated with lower 5-year OS (P < 0.05). CONCLUSION: Elderly GC patients with higher TNM staging, longer tumor diameters, high levels of CXCL13 and PECAM-1 had an increased risk of poor prognosis. Serum CXCL13 and PECAM-1 can be used as effective indicators for diagnosis and prognosis of elderly patients with GC, and can predict the 5-year OS in patients.

The free amino acid profiles and metabolic biomarkers of predicting the chemotherapeutic response in advanced sarcoma patients.

PURPOSE: Metabolomics is an emerging field in cancer research. Plasma free amino acid profiles (PFAAs) have shown different features in various cancers, but the characteristic in advanced sarcoma remains unclear. We aimed to uncover the specific PFAAs in advanced sarcoma and to find the relationship between the altering of PFAAs and response to chemotherapy. PATIENTS AND METHODS: We analyzed the differences in PFAAs between 23 sarcoma patients and 30 healthy subjects basing on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we compared the dynamics of PFAAs after chemotherapy between improvement group and deterioration group. RESULTS: We identified seven biological differential amino acids and four pathways which were perturbed in the sarcoma patients compared with healthy subjects. After one cycle chemotherapy, the levels of γ-aminobutyric acid (GABA) and carnosine (Car) decreased significantly in the improvement group but not in deterioration group. The levels of α-aminobutyric acid (Abu) increased significantly in the deterioration group but not in the improvement group. CONCLUSION: Our study suggests the potential specific PFAAs in sarcoma patients. The unusual amino acids and metabolic pathways may provide ideas for clinical drugs targeting therapy. Three amino acids including Car, GABA and Abu may be metabolic biomarkers playing a role in dynamic monitoring of the therapeutic effect.

Clinicopathological and prognostic value of hypoxia-inducible factor-1α in breast cancer: a meta-analysis including 5177 patients.

PURPOSE: Mounting studies have investigated the clinicopathological and prognostic value of hypoxia-inducible factor-1α (HIF-1α) in breast cancer (BC), yet conclusions remain controversial. Therefore, we conducted this meta-analysis to clarify this issue. METHODS: All relevant studies were searched using Cochrane Library, Web of Science, PubMed, and EMBASE online databases. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate the clinicopathological and prognostic value of HIF-1α, respectively. Subgroup analysis and sensitivity analysis were performed to investigate heterogeneity and stability of the results. Begg's funnel plot and Egger's test were used to examine publication bias. RESULTS: A total of 31 eligible studies including 5177 subjects were enrolled. Of these, 25 studies assessed the prognostic role of HIF-1α and included 4546 individuals. Twenty-three studies involving 3277 individuals evaluated the clinicopathological significance of HIF-1α. High expression level of HIF-1α was correlated with poor overall survival (OS) (HR = 1.59, 95% CI = 1.40-1.80, P < 0.001), disease-free survival (DFS) (HR = 1.87, 95% CI = 1.53-2.28, P < 0.001), relapse-free survival (HR = 1.36, 95% CI = 1.07-1.73, P = 0.001), and cancer-specific survival (HR = 1.55, 95% CI = 1.10-2.19, P = 0.012). Pooled data from studies using multivariate survival analysis also showed that HIF-1α expression was associated with worse OS (HR = 1.59, 95% CI = 1.32-1.92, P < 0.001) and DFS (HR = 1.60, 95% CI = 1.39-1.84, P < 0.001). Additionally, high HIF-1α expression was associated with advanced tumor-node-metastasis stage, positive lymph-node status, negative ER status, ductal type, advanced histologic grade, high Ki67 expression, and strong VEGF expression. CONCLUSION: HIF-1α might serve as an independent prognostic biomarker and a promising therapeutic target for BC. Future large-scale prospective randomized trials are needed to confirm our findings.

THBS1 facilitates colorectal liver metastasis through enhancing epithelial-mesenchymal transition.

OBJECTIVE: Liver metastasis is one of the major causes of cancer-related death in patients with colorectal cancer (CRC). The purpose of this study was to identify specific molecules which are involved in colorectal liver metastasis (CRLM). MATERIALS AND METHODS: In this study, we employed TMT (tandem mass tags)-labeling combined with liquid chromatography-mass spectrometry technology to do comparative analyses of proteomics between the primary tumor specimens derived from colorectal cancer patients with or without liver metastasis. Pathway enrichment analyses were performed using DAVID database. The crucial molecules were identified through protein-protein interaction network. Immunohistochemistry (IHC) was employed to analyze the expression of THBS1 (thrombospondin-1) in CRC tissues. Finally, transwell cell migration and invasion assays were performed to explore the roles of THBS1 in CRC cell migration and invasion. RESULTS: We found that the expression of 311 proteins was dysregulated in CRLM using quantitative proteomics. Among these proteins, we identified FN1, TIMP1, THBS1, POSTN and VCAN as five crucial proteins in CRLM by analysis in silico. IHC assay revealed that increased THBS1 expression was significantly correlated with liver metastasis as well as poor prognosis of CRC patients. GEO data analysis also suggests that upregulated mRNA level of THBS1 is also associated with shorter overall survival of CRC patients. Moreover, THBS1 depletion inhibited migration and invasion of CRC cells through attenuating epithelial-mesenchymal transition. Co-expression analyses with TCGA data indicated that THBS1 is co-expressed with mesenchymal markers, including Vimentin, N-cadherin, Snail1 and Twist1 in CRC tissues. CONCLUSIONS: By collecting the omics data with functional studies, the present results reveal that THBS1 facilitates colorectal liver metastasis through promoting epithelial-mesenchymal transition. This understanding of molecular roles of THBS1 in CRLM may be promising to develop targeted therapies to prolong survival in CRC patients.

Is one brachytherapy fraction of 7 Gy similar to more fractions after external beam irradiation in postoperative endometrial carcinoma?

PURPOSE: To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. METHODS/MATERIAL: From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4-6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5-6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. STATISTICS: the chi-square test. RESULTS: The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. CONCLUSIONS: One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.

Effects of Glutamine on the Mucosal Structure and Immune Cells in the Intestines of Broiler Chickens Challenged with Salmonella Enteritidis

The aim of this study was to investigate the effects of glutamine (Gln) on the intestinal mucosal structure and immune cells of broilers infected with Salmonella Enteritidis. 160 1-d-old commercial Arbor Acres (AA) broilers were randomly selected to receive one of four treatments, each of which had 5 replicates. Each replicate consisted of 8 chicks subjected to a 21-d feeding trial. Group I served as the unchallenged (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. The birds in groups III and IV were treated with 0.5% and 1.0% Gln. The results showed that S. Enteritidis infection led to a decrease in the relative length and weight, villus height:crypt depth (VH:CD) of the jejunum and ileum, the number of intraepithelial lymphocyte cells, and number of goblet cells and an increase in the number of mast goblet cells compared with the measurements of these parameters in the CON group (p 0.05). In addition, the Gln groups had increased relative length and weight, VH:CD of the jejunum and ileum, numbers of intraepithelial lymphocyte cells, and numbers of goblet cells and decreased crypt depth in the jejunum and ileum and numbers of mast goblet cells compared with the measurements of these parameters in the SCC group (p 0.05). It was concluded that Gln added to broiler diets can effectively alleviate the intestinal mucosal damage caused by S. Enteritidis infection and improve its normal defense barrier function.(AU)

Effects of Glutamine on the Mucosal Structure and Immune Cells in the Intestines of Broiler Chickens Challenged with Salmonella Enteritidis

The aim of this study was to investigate the effects of glutamine (Gln) on the intestinal mucosal structure and immune cells of broilers infected with Salmonella Enteritidis. 160 1-d-old commercial Arbor Acres (AA) broilers were randomly selected to receive one of four treatments, each of which had 5 replicates. Each replicate consisted of 8 chicks subjected to a 21-d feeding trial. Group I served as the unchallenged (CON). All birds in groups II (SCC) - IV were challenged with 2.0 × 104 CFU/mL of S. Enteritidis. The birds in groups III and IV were treated with 0.5% and 1.0% Gln. The results showed that S. Enteritidis infection led to a decrease in the relative length and weight, villus height:crypt depth (VH:CD) of the jejunum and ileum, the number of intraepithelial lymphocyte cells, and number of goblet cells and an increase in the number of mast goblet cells compared with the measurements of these parameters in the CON group (p 0.05). In addition, the Gln groups had increased relative length and weight, VH:CD of the jejunum and ileum, numbers of intraepithelial lymphocyte cells, and numbers of goblet cells and decreased crypt depth in the jejunum and ileum and numbers of mast goblet cells compared with the measurements of these parameters in the SCC group (p 0.05). It was concluded that Gln added to broiler diets can effectively alleviate the intestinal mucosal damage caused by S. Enteritidis infection and improve its normal defense barrier function.