The spatiotemporal associations between esophageal and gastric cancers provide evidence for its joint endoscopic screening in China: a population-based study.

BACKGROUND: The spatiotemporal epidemiological evidence supporting joint endoscopic screening for esophageal cancer (EC) and gastric cancer (GC) remains limited. This study aims to identify combined high-risk regions for EC and GC and determine optimal areas for joint and separate endoscopic screening. METHODS: We analyzed the association of incidence trends between EC and GC in cancer registry areas across China from 2006 to 2016 using spatiotemporal statistical methods. Based on these analyses, we divided different combined risk regions for EC and GC to implement joint endoscopic screening. RESULTS: From 2006 to 2016, national incidence trends for both EC and GC showed a decline, with an average annual percentage change of -3.15 (95% confidence interval [CI]: -5.33 to -0.92) for EC and -3.78 (95% CI: -4.98 to -2.56) for GC. A grey comprehensive correlation analysis revealed a strong temporal association between the incidence trends of EC and GC, with correlations of 79.00% (95% CI: 77.85 to 80.14) in males and 77.62% (95% CI: 76.50 to 78.73) in females. Geographic patterns of EC and GC varied, demonstrating both homogeneity and heterogeneity across different regions. The cancer registry areas were classified into seven distinct combined risk regions, with 33 areas identified as high-risk for both EC and GC, highlighting these regions as priorities for joint endoscopic screening. CONCLUSION: This study demonstrates a significant spatiotemporal association between EC and GC. The identified combined risk regions provide a valuable basis for optimizing joint endoscopic screening strategies for these cancers.

Perception Methods for Adverse Weather Based on Vehicle Infrastructure Cooperation System: A Review.

Environment perception plays a crucial role in autonomous driving technology. However, various factors such as adverse weather conditions and limitations in sensing equipment contribute to low perception accuracy and a restricted field of view. As a result, intelligent connected vehicles (ICVs) are currently only capable of achieving autonomous driving in specific scenarios. This paper conducts an analysis of the current studies on image or point cloud processing and cooperative perception, and summarizes three key aspects: data pre-processing methods, multi-sensor data fusion methods, and vehicle-infrastructure cooperative perception methods. Data pre-processing methods summarize the processing of point cloud data and image data in snow, rain and fog. Multi-sensor data fusion methods analyze the studies on image fusion, point cloud fusion and image-point cloud fusion. Because communication channel resources are limited, the vehicle-infrastructure cooperative perception methods discuss the fusion and sharing strategies for cooperative perception information to expand the range of perception for ICVs and achieve an optimal distribution of perception information. Finally, according to the analysis of the existing studies, the paper proposes future research directions for cooperative perception in adverse weather conditions.

Controllably Self-Assembled Antibacterial Nanofibrils Based on Insect Cuticle Protein for Infectious Wound Healing.

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.

Spatiotemporal Patterns of Esophageal Cancer Burden Attributable to Behavioral, Metabolic, and Dietary Risk Factors From 1990 to 2019: Longitudinal Observational Study.

BACKGROUND: Esophageal cancer (EC) is the sixth leading cause of cancer-related burden with distinct regional variations globally. Although the burden of EC has decreased, the specific reasons for this decline are still unclear. OBJECTIVE: This study aims to uncover the spatiotemporal patterns of EC risk-attributable burden in 204 countries and territories from 1990 to 2019 so that prevention and control strategies of EC can be prioritized worldwide. METHODS: We extracted EC risk-attributable deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMRs), and age-standardized DALY rates (ASDRs) from the global burden of disease (GBD) study from 1990 to 2019, in terms of behavioral, metabolic, and dietary factors by age, sex, and geographical location. Average annual percentage change (AAPC) was used to assess the long-term trends in the ASMRs and ASDRs of EC due to specific risk factors. RESULTS: Between 1990 and 2019, the greatest decrease in EC burden was attributed to low intake of fruits and vegetables. An AAPC of -2.96 (95% CI -3.28 to -2.63) and -3.12 (95% CI -3.44 to -2.79) in ASMR and ASDR was attributable to a low-fruit diet, while an AAPC of -3.60 (95% CI -3.84 to -3.36) and -3.64 (95% CI -3.92 to -3.35) in ASMR and ASDR was attributed to a low-vegetable diet. However, the trends in ASMRs and ASDRs due to high BMI showed significant increases with an AAPC of 0.52 (95% CI 0.29-0.75) in ASMR and 0.42 (95% CI 0.18-0.66) in ASDR from 1990 to 2019 compared to significant decreases in other attributable risks with AAPC<0 (P<.05). East Asia had the largest decrease in EC burden due to low-vegetable diets, with an AAPC of -11.00 (95% CI -11.32 to -10.67) in ASMR and -11.81 (95% CI -12.21 to -11.41) in ASDR, followed by Central Asia, whereas Western Sub-Saharan Africa had the largest increase in ASMR and ASDR due to high BMI, with an AAPC of 3.28 (95% CI 3.14-3.42) and 3.09 (95% CI 2.96-3.22), respectively. China had the highest EC burden attributed to smoking, alcohol use, high BMI, and low-fruit diets. Between 1990 and 2019, there was a significant decrease in EC burden attributable to smoking, alcohol use, chewing tobacco, low-fruit diets, and low-vegetable diets in most countries, wherein a significant increase in the EC burden was due to high BMI. CONCLUSIONS: Our study shows that smoking and alcohol consumption are still the leading risk factors of EC burden and that EC burden attributable to low intake of fruits and vegetables has shown the largest decline recently. The risks of ASMRs and ASDRs of EC showed distinct spatiotemporal patterns, and future studies should focus on the upward trend in the EC burden attributed to high BMI.

LINC-PINT suppresses cisplatin resistance in gastric cancer by inhibiting autophagy activation via epigenetic silencing of ATG5 by EZH2.

Resistance to cisplatin (DDP) is a major obstacle in the clinical treatment of advanced gastric cancer (GC). Long noncoding RNA (lncRNA) play a significant regulatory role in the development and drug resistance of GC. In this study, we reported that the lncRNA LINC-PINT was downregulated in DDP-resistant GC cells. Functional studies showed that LINC-PINT inhibited proliferation and migration of DDP-resistant GC cells in vitro, and overexpression of LINC-PINT could enhance the sensitivity of DDP-resistant GC cells to DDP. Further investigation revealed that LINC-PINT recruited enhancer of zeste homolog 2 (EZH2) to the promotor of ATG5 to inhibit its transcription, leading to the suppression of autophagy and DDP resensitization. Collectively, our results revealed how the LINC-PINT/EZH2/ATG5 axis regulates autophagy and DDP resistance in GC. These data suggest that LINC-PINT may be a potential therapeutic target in GC.

DLX6-AS1 activated by H3K4me1 enhanced secondary cisplatin resistance of lung squamous cell carcinoma through modulating miR-181a-5p/miR-382-5p/CELF1 axis.

Cisplatin (CDDP) based chemotherapy is widely used as the first-line strategy in treating non-small cell lung cancer (NSCLC), especially lung squamous cell carcinoma (LUSC). However, secondary cisplatin resistance majorly undermines the cisplatin efficacy leading to a worse prognosis. In this respect, we have identified the role of the DLX6-AS1/miR-181a-5p/miR-382-5p/CELF1 axis in regulating cisplatin resistance of LUSC. qRT-PCR and Western blot analysis were applied to detect gene expression. Transwell assay was used to evaluate the migration and invasion ability of LUSC cells. CCK-8 assay was used to investigate the IC50 of LUSC cells. Flow cytometry was used to test cell apoptosis rate. RNA pull-down and Dual luciferase reporter gene assay were performed to evaluate the crosstalk. DLX6-AS1 was aberrantly high expressed in LUSC tissues and cell lines, and negatively correlated with miR-181a-5p and miR-382-5p expression. DLX6-AS1 expression was enhanced by H3K4me1 in cisplatin resistant LUSC cells. Besides, DLX6-AS1 knockdown led to impaired IC50 of cisplatin resistant LUSC cells. Furthermore, DLX6-AS1 interacted with miR-181a-5p and miR-382-5p to regulate CELF1 expression and thereby mediated the cisplatin sensitivity of cisplatin resistant LUSC cells. DLX6-AS1 induced by H3K4me1 played an important role in promoting secondary cisplatin resistance of LUSC through regulating the miR-181a-5p/miR-382-5p/CELF1 axis. Therefore, targeting DLX6-AS1 might be a novel way of reversing secondary cisplatin resistance in LUSC.

Radiation induces NORAD expression to promote ESCC radiotherapy resistance via EEPD1/ATR/Chk1 signalling and by inhibiting pri-miR-199a1 processing and the exosomal transfer of miR-199a-5p.

BACKGROUND: Radioresistance, a poorly understood phenomenon, results in the failure of radiotherapy and subsequent local recurrence, threatening a large proportion of patients with ESCC. To date, lncRNAs have been reported to be involved in diverse biological processes, including radioresistance. METHODS: FISH and qRT-PCR were adopted to examine the expression and localization of lncRNA-NORAD, pri-miR-199a1 and miR-199a-5p. Electron microscopy and nanoparticle tracking analysis (NTA) were conducted to observe and identify exosomes. High-throughput microRNAs sequencing and TMT mass spectrometry were performed to identify the functional miRNA and proteins. A series of in vitro and in vivo experiments were performed to investigate the biological effect of NORAD. ChIP, RIP-qPCR, co-IP and dual-luciferase reporter assays were conducted to explore the interaction of related RNAs and proteins. RESULTS: We show here that DNA damage activates the noncoding RNA NORAD, which is critical for ESCC radioresistance. NORAD was expressed at high levels in radioresistant ESCC cells. Radiation treatment promotes NORAD expression by enhancing H3K4me2 enrichment in its sequence. NORAD knockdown cells exhibit significant hypersensitivity to radiation in vivo and in vitro. NORAD is required to initiate the repair and restart of stalled forks, G2 cycle arrest and homologous recombination repair upon radiation treatment. Mechanistically, NORAD inhibits miR-199a-5p expression by competitively binding PUM1 from pri-miR-199a1, inhibiting the processing of pri-miR-199a1. Mature miR-199a-5p in NORAD knockdown cells is packaged into exosomes; miR-199a-5p restores the radiosensitivity of radioresistant cells by targeting EEPD1 and then inhibiting the ATR/Chk1 signalling pathway. Simultaneously, NORAD knockdown inhibits the ubiquitination of PD-L1, leading to a better response to radiation and anti-PD-1 treatment in a mouse model. CONCLUSIONS: Based on the findings of this study, lncRNA-NORAD represents a potential treatment target for improving the efficiency of immunotherapy in combination with radiation in ESCC.

A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer.

BACKGROUND: Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo. METHODS: qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients' cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth. RESULTS: LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume. CONCLUSION: In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.

Oxidative stress activates NORAD expression by H3K27ac and promotes oxaliplatin resistance in gastric cancer by enhancing autophagy flux via targeting the miR-433-3p.

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.

LINC00461 Overexpression Can Induce Docetaxel Resistance in Breast Cancer by Interacting with miR-411-5p.

PURPOSE: Breast cancer (BC) is the most common malignant cancer in women worldwide. Recently, long non-coding RNAs (LncRNAs) have been reported to have essential roles in BC tumorigenesis. PATIENTS AND METHODS: Tumor and adjacent non-tumor tissue samples were collected from patients with BC (n = 168) for comparison of LncRNA and miRNA expression levels. Patient clinical, demographic, and molecular data were analyzed by univariate and multivariate methods to identify factors associated with patient survival, and a nomogram was generated using significant risk/protective factors. Further, analyses of LINC00461 and miR-411-5p expression and function were conducted in BC and normal breast epithelial cell lines, by quantitative RT-PCR, cell proliferation, wound-healing, RNA pull-down, RNA immunoprecipitation, and luciferase assays. Docetaxel (DTX)-resistant BC cell lines were also generated and used to assess the roles of LINC00461 and miR-411-5p in drug resistance. RESULTS: LINC00461 was up-regulated in BC tissues relative to adjacent non-tumor samples, and expression of LINC00461 was correlated with poor patient prognosis. LINC00461 knockdown could inhibit proliferation of BC cells in vitro. Further, LINC00461 expression was higher in DTX-resistant than in non-resistant BC cell lines. Our data support a role for LINC00461 as a competitive endogenous RNA sponge involved in regulation of miR-411-5p expression in BC. miR-411-5p was down-regulated in both BC tissues and cell lines, with levels negatively correlated with those of LINC00461. Moreover, miR-411-5p was down-regulated in DTX-resistant BC cell lines compared with non-resistant cell lines. CONCLUSION: In conclusion, LINC00461 promotes proliferation, migration, and DTX-resistance in BC by acting as a sponge for miR-411-5p. This process represents a potential therapeutic target for patients with BC.

Alantolactone enhances gemcitabine sensitivity of lung cancer cells through the reactive oxygen species-mediated endoplasmic reticulum stress and Akt/GSK3ß pathway.

Lung cancer is one of the leading causes of cancer­associated mortality in China and globally. Gemcitabine (GEM), as a first­line therapeutic drug, has been used to treat lung cancer, but GEM resistance poses a major limitation on the efficacy of GEM chemotherapy. Alantolactone (ALT), a sesquiterpene lactone compound isolated from Inula helenium, has been identified to exert anticancer activity in various types of cancer, including breast, pancreatic, lung squamous and colorectal cancer. However, the underlying mechanisms of the anticancer activity of ALT in lung cancer remain to be fully elucidated. The present study aimed to determine whether ALT enhances the anticancer efficacy of GEM in lung cancer cells and investigated the underlying mechanisms. The cell viability was assessed with a Cell Counting Kit­8 assay. The cell cycle, apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression of cell cycle­associated and apoptosis­associated proteins were determined by western blot analysis. The results demonstrated that ALT inhibited cell growth and induced S­phase arrest and cell apoptosis in A549 and NCI­H520 cells. Furthermore, ALT increased the level of ROS, inhibited the Akt/glycogen synthase kinase (GSK)3ß pathway and induced endoplasmic reticulum (ER) stress in A549 and NCI­H520 cells. Additionally, ALT treatment sensitized lung cancer cells to GEM. Analysis of the molecular mechanisms further revealed that ALT enhanced the anticancer effects of GEM via ROS­mediated activation of the Akt/GSK3ß and ER stress pathways. In conclusion, combined treatment with ALT and GEM may have potential as a clinical strategy for lung cancer treatment.

Natriuretic peptide receptor a promotes breast cancer development by upregulating MMP9.

Natriuretic peptide receptor A (NPRA), one of the natriuretic peptide receptors, plays important roles in circulatory system. Recently some studies showed that NPRA was involved in tumorigenesis, however, its role in the development of breast cancer remains unclear. In this study, we observed that NPRA expression was upregulated in breast cancer tissues and NPRA high expression was associated with poor clinicopathological features. In addition, we found that patients with high NPRA expression had a worse 5-year survival and NPRA was an independent factor for predicting the prognosis of breast cancer patients. Knocking down NPRA expression reduced the proliferation, migration and invasion of breast cancer cells. Overexpressing NPRA was able to enhance the malignant behaviors of breast cancer cells. Furthermore, NPRA promoted the invasive phenotype through upregulating matrix metalloproteinase-9 (MMP9). Mechanistically, NPRA increased MMP9 expression through activating STAT3. We identified that NPRA might serve as a prognostic marker and p-STAT3 and MMP9 could be a potential target of NPRA in breast cancer patients.

Survival analysis for male ductal and lobular breast cancer patients with different stages.

AIM: We aimed to investigate risk factors and current treatment effects in male breast cancer patients. METHODS: Kaplan-Meier plot, log-rank test, COX model, nomograms and propensity score matching were used. RESULTS: Among stage I-III patients, surgery was associated with better prognosis. In subgroup analysis, performing surgery and no radiation or chemotherapy led to worse prognosis in research group. Among stage IV patients, chemotherapy correlated with better prognosis and radiation led to better breast cancer-specific survival. In addition, brain and liver metastasis correlated with worse prognosis; and lung correlated with worse breast cancer-specific survival. CONCLUSION: For stage I-III patients, surgery and chemotherapy were recommended. And not applying radiation or chemotherapy could be carefully considered for ER(+) HER-2(-) patients. For stage IV patients, chemotherapy and radiation were commended.

Nomograms to predict survival rates for esophageal cancer patients with malignant behaviors based on ICD-0-3.

AIM: We aimed to investigate the effect of current treatment based on stage and histology type, which were important factors for treating esophageal cancer. METHODS: Log-rank test, COX and nomograms were used for survival analysis. DCA, C-index and calibration curves were used for validation. RESULTS: A total of 3224 patients were recruited. As for cT2-T4aM0 patients, chemotherapy and radiation prolonged overall survival (OS) for esophageal squamous cell carcinoma (ESCC) and chemotherapy improved OS for esophageal adenocarcinoma (EAC). Meanwhile, neoadjuvant radiotherapy had longer OS than adjuvant radiotherapy for ESCC. As for T4b patients, radiation and chemotherapy correlated with better OS for ESCC and chemotherapy prolonged OS for EAC. CONCLUSION: Neoadjuvant radiotherapy might be optimal for cT2-T4aM0 ESCC. Radiation was recommended for T4b ESCC while chemotherapy was recommended for T4b EAC.

Baicalein suppress EMT of breast cancer by mediating tumor-associated macrophages polarization.

Tumor associated macrophages (TAMs) are the main infiltrating component in the tumor microenvironment and play an important role in cancer progression. Baicalein has a wide range of pharmacological properties. This study explores the potential effect of baicalein on macrophages polarization and epithelial-mesenchymal transition (EMT) of breast cancer. Co-culture system was established to evaluate the interaction between TAMs and breast cancer cells. Then the role of baicalein in modulating TAMs function was assessed. Finally, breast cancer mouse model was established to study the underlying mechanism. In vitro experiments showed that co-culture with M2 macrophages significantly enhanced EMT of both MDA-MB-231 and MCF-7 breast cancer cells. Baicalein could regulate polarization of M2 and attenuate TGF-ß1 secretion. In vivo experiments showed that compared with the MDA-MB-231 + M2 group, tumor growth and metastasis of baicalein + MDA-MB-231 + M2 group was significantly inhibited, with smaller tumor size and decreased lung metastasis lesions. Our findings suggest that the regulation of TAMs may be a novel mechanism underlying the anti-tumor effects of baicalein in breast cancer.

LINC00657 played oncogenic roles in esophageal squamous cell carcinoma by targeting miR-615-3p and JunB.

BACKGROUND: The prognosis of esophageal squamous cell carcinoma (ESCC) is relatively poor due to the absence of efficient treatment. In this manuscript, we have investigated the specific roles and molecular mechanisms of LINC00657 to order to identify novel therapeutic targets for ESCC. METHOD: The LINC00657 expression in ESCC tissues and cell lines were evaluated by quantitative real-time PCR. The expression of LINC00657 in ESCC cells was regulated by lentivirus transfection. Online bioinformatics analysis tools were used to predict the potential targets of LINC00657 and miR-615-3p. TCGA database was used to analyze the prognosis of ESCC patients. Transwell, wound healing assay and MTT were performed to investigate the ESCC cells' biological functions. JunB expression was evaluated by Western blot. RESULT: LINC00657 was moderately increased in ESCC both in vivo and in vitro and up regulated by irradiation. LINC00657 knockdown could inhibit the migration and proliferation of ESCC cells. And downregulation of LINC00657 significantly enhanced the radio-sensitivity. Moreover, LINC00657 could act as a ceRNA to increase the expression of JunB by binding to miR-615-3p. Meanwhile, overexpression of miR-615-3p resulted in anti-tumor effects and led to the down-regulation of JunB. Survival analysis from TCGA indicated that ESCC patients with higher JunB expression had significant poorer prognosis. CONCLUSION: LINC00657 might be involved in regulating ESCC's response to radiation; and it functioned as an oncogene in ESCC by targeting miR-615-3p and JunB, providing novel potential therapeutic targets.

Plasma phospholipase A2 activity may serve as a novel diagnostic biomarker for the diagnosis of breast cancer.

Previous studies have indicated that phospholipase A2 (PLA2) may be associated with tumorigenesis in human tissues. The present study aimed to investigate the association between plasma PLA2 activity and the breast cancer (BC) status of patients. Increased plasma PLA2 activity was detected in patients with breast cancer when compared with healthy controls. Plasma samples were obtained from patients with BC (n=169), patients with benign disease (BD; n=80) and healthy controls (n=81). PLA2 activity was assessed using a quantitative fluorescent assay with selective inhibitors. It was demonstrated that increased PLA2 and secretory PLA2 (sPLA2) activity was associated with tumor stage, particularly in patients with late-stage disease. Additionally, smoking, alcohol consumption, body mass index (BMI) and age of patients did not have a significant effect on PLA2 activity. Analysis of receiver operating characteristic curves revealed that plasma PLA2 and sPLA2 activities were increased in BC patients compared with healthy controls. It was concluded that plasma PLA2 activity may serve as a biomarker for patients with BC.

miR-615-3p promotes proliferation and migration and inhibits apoptosis through its potential target CELF2 in gastric cancer.

Gastric cancer incidence is relatively higher in China than that in developed countries; however, molecular mechanisms considering the initiation and progression of gastric cancer are still unclear. For decades, numerous microRNAs have been found to regulate a wide range of biological functions in gastric cancer. However, the oncogenic function of miR-615-3p in gastric cancer has not been reported to date. With the help of gene and microRNA chips in 10 patients, we were able to screen differential expressed genes and microRNAs compared with normal gastric tissues. After that, online bioinformatics analysis tools were used to predict microRNAs' potential targets. As a result, miR-615-3p and its potential target, CELF2, were selected for further experiments. QRT-PCR and western blot results indicated the aberrant high expression of miR-615-3p and low expression of CELF2 in gastric cancer both in vivo and in vitro. Moreover, miR-615-3p expression correlated to T and M stage. Up regulation of miR-615-3p inhibited the apoptosis, promoted proliferation and migration and led to the down-regulation of CELF2. Meanwhile, down-regulation of miR-615-3p resulted in anti-tumor effects. Immunochemistry staining of CELF2 showed its association with T, N and M stage. In addition, overexpression of CELF2 could reverse miR-615-3p's oncogenic functions stated before. These findings indicate that miR-615-3p promotes gastric cancer proliferation and migration by suppressing CELF2 expression for the first time, providing clues for future clinical practices.

Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma.

Radiotherapy is one of the common treatments for esophageal squamous cell carcinoma (ESCC). Yet, local recurrence led by radioresistance is still not solved. Lobaplatin (LBP) is known to have powerful clinical anti-tumor activities in various tumors, but its effect in radiotherapy is rarely studied. Here we report that LBP is a promising radiosensitizer for ESCC. We treated ESCC cells with LBP and radiation, both separately and in combination. Untreated cells were set as control groups. We found that LBP inhibited ESCC cell growth and enhanced their radiosensitivity. LBP also impeded the tumor growth in vivo. LBP combined with radiation significantly increased ESCC cell apoptosis. Meanwhile, LBP obviously decreased the expression of cancer stem cells biomarker CD271 both in vitro and in vivo. The molecular mechanism was related to the downregulation of Bcl-2/Bax ratio, PI3K and p-AKT (Ser473) expression. Taken together, our findings indicated that LBP could enhance the radiosensitivity of ESCC cells by increasing radiation-induced apoptosis, attenuating cancer stemness and inhibiting PI3K/AKT pathway. These results provide a foundation for the combined therapy of radiation and LBP for ESCC in clinical practice.

MYC overexpression with its prognostic and clinicopathological significance in breast cancer.

BACKGROUND: Proto-oncogene MYC has been indicated to promote progression of many cancers. However, prognostic and clinicopathological significance of MYC in breast cancer need further evaluation. METHODS: We searched EMBASE and PubMed databases to find useful studies. We analyzed relationships between high MYC expression and prognostic data/ clinicopathological features through hazard ratio (HR) and odds ratio (OR). Each statistical test was two-sided. RESULTS: There were 29 studies (36 cohorts) with 12621 patients enrolled in our study The MYC overexpression was associated with worse DFS/RFS (disease/relapse free survival) in 11 studies (16 cohorts) with 5390 patients, and OS (overall survival) of 7 studies (8 cohorts) with 2672 patients. Subgroup analysis according to ethnicity/technique/data source displayed that MYC overexpression was associated with poor DFS/RFS in FISH, other technique, all data source and Asian/Non-Asian subgroup, and worse OS in all subgroups. In addition, MYC overexpression was related to large tumor size, high histologic grade, lymph node metastasis, negative hormone receptors and positive Ki67 expression. CONCLUSIONS: Our results showed that MYC overexpression was associated with worse prognosis and high risk of breast cancer, especially in patients with negative hormone receptors, which highlighted the potential of MYC as a significant prognostic biomarker of breast cancer.