Exosomes in tumor-stroma crosstalk: Shaping the immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) is a multifaceted disease characterized by a complex interaction between tumor cells and the surrounding microenvironment. Within this intricate landscape, exosomes have emerged as pivotal players in the tumor-stroma crosstalk, influencing the immune microenvironment of CRC. These nano-sized vesicles, secreted by both tumoral and stromal cells, serve as molecular transporters, delivering a heterogeneous mix of biomolecules such as RNAs, proteins, and lipids. In the CRC context, exosomes exert dual roles: they promote tumor growth, metastasis, and immune escape by altering immune cell functions and activating oncogenic signaling pathways and offer potential as biomarkers for early CRC detection and treatment targets. This review delves into the multifunctional roles of exosomes in the CRC immune microenvironment, highlighting their potential implications for future therapeutic strategies and clinical outcomes.

Semantic Retrieval of Remote Sensing Images Based on the Bag-of-Words Association Mapping Method.

With the increasing demand for remote sensing image applications, extracting the required images from a huge set of remote sensing images has become a hot topic. The previous retrieval methods cannot guarantee the efficiency, accuracy, and interpretability in the retrieval process. Therefore, we propose a bag-of-words association mapping method that can explain the semantic derivation process of remote sensing images. The method constructs associations between low-level features and high-level semantics through visual feature word packets. An improved FP-Growth method is proposed to achieve the construction of strong association rules to semantics. A feedback mechanism is established to improve the accuracy of subsequent retrievals by reducing the semantic probability of incorrect retrieval results. The public datasets AID and NWPU-RESISC45 were used to validate these experiments. The experimental results show that the average accuracies of the two datasets reach 87.5% and 90.8%, which are 22.5% and 20.3% higher than VGG16, and 17.6% and 15.6% higher than ResNet18, respectively. The experimental results were able to validate the effectiveness of our proposed method.

SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression.

BACKGROUND: This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. METHODS: LncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised. RESULTS: SNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P < 0.05). Additionally, nicotine not merely elevated UCA1 and HIF-1α expressions in CRC cells, but also facilitated proliferation and metastasis of CRC cells (P < 0.05). CONCLUSIONS: SNP rs12982687 was involved in smoking-triggered CRC progression, given its influence on UCA1's binding with miR-873-5p and HIF-1 signaling.

SAV1, regulated by microRNA-21, suppresses tumor growth in colorectal cancer.

This study investigated the role and action of the Salvador 1 protein (SAV1, also called WW45) in colorectal cancer (CRC). For this, CRC SW480 and HCT116 cells were infected with lentiviruses of SAV1 overexpression vector (lenti-SAV1) and SAV1 short hairpin RNA (sh-SAV1) to overexpress and silence SAV1 respectively, or transfected with microRNA-21 (miR-21) mimic to overexpress miR-21. Relative mRNA levels of SAV1 and relative miR-21 levels in CRC tissues or cells were detected. The effects of SAV1 and miR-21 on cell proliferation and apoptosis were evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and annexin V - fluorescein isothiocyanate (FITC) - propidium iodide (PI) flow cytometry, respectively. Our results revealed that SAV1 was downregulated in CRC tissues compared with the adjacent noncancerous tissues. Furthermore, SAV1 overexpression inhibited proliferation and promoted apoptosis in SW480 and HCT116 cells, whereas knockdown of SAV1 exerted the opposite effect. Additionally, the tumorigenesis of SW480 cells in xenografted mice was significantly inhibited by SAV1 overexpression but promoted by SAV1 knockdown. MiR-21 levels significantly and negatively correlated with SAV1 expression in CRC tissues. More importantly, miR-21 overexpression significantly abolished the SAV1-mediated inhibition of proliferation and stimulation of apoptosis of SW480. In conclusion, SAV1 suppresses tumor growth in CRC and is regulated by miR-21.

Detection of Lung Contour with Closed Principal Curve and Machine Learning.

Radiation therapy plays an essential role in the treatment of cancer. In radiation therapy, the ideal radiation doses are delivered to the observed tumor while not affecting neighboring normal tissues. In three-dimensional computed tomography (3D-CT) scans, the contours of tumors and organs-at-risk (OARs) are often manually delineated by radiologists. The task is complicated and time-consuming, and the manually delineated results will be variable from different radiologists. We propose a semi-supervised contour detection algorithm, which firstly uses a few points of region of interest (ROI) as an approximate initialization. Then the data sequences are achieved by the closed polygonal line (CPL) algorithm, where the data sequences consist of the ordered projection indexes and the corresponding initial points. Finally, the smooth lung contour can be obtained, when the data sequences are trained by the backpropagation neural network model (BNNM). We use the private clinical dataset and the public Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) dataset to measure the accuracy of the presented method, respectively. To the private dataset, experimental results on the initial points which are as low as 15% of the manually delineated points show that the Dice coefficient reaches up to 0.95 and the global error is as low as 1.47 × 10-2. The performance of the proposed algorithm is also better than the cubic spline interpolation (CSI) algorithm. While on the public LIDC-IDRI dataset, our method achieves superior segmentation performance with average Dice of 0.83.

Defining the restriction point in normal asynchronous human peripheral blood lymphocytes.

Although the restriction point (R-point) was proposed in animal cells several decades ago, its existence in normal cells is still controversial, because, in most studies, long-term cultured cell lines rather than primary normal cells were used. Furthermore, cell synchronization was generally applied, resulting in growth imbalance between DNA synthesis and protein expression in cells. Finally, R-point was originally proposed as a unique arrest point that may be in G0 phase; however, generally believed R-point locates within G1 phase. Thus, up to now, there is no solid experimental evidence that supports the existence of R-point in asynchronous primary normal cells. In this study, we used freshly purified peripheral human blood lymphocytes, as asynchronous primary normal cells, to confirm the existence of restriction point in G1 not G0 phase. Our findings may help uncover the mystery of the deregulation of cell cycle progression in malignant tumors. © 2013 International Society for Advancement of Cytometry.

The comparison of self-gripping mesh and conventional mesh in laparoscopic inguinal hernia repair: the results of meta-analysis.

Self-gripping mesh is widely used in laparoscopic inguinal hernia repair and some researches report its advantages compared with conventional mesh. The aim of this study was to assess outcomes of self-gripping mesh and conventional mesh in laparoscopic inguinal hernia repair. A systematic literature review was undertaken to identify studies comparing the results of self-gripping mesh and conventional mesh in laparoscopic inguinal hernia repair. Outcomes, including recurrence, chronic pain, operation time, hematoma, seroma and infection, were measured. Four randomized controlled trials and 1 prospective comparative study were analyzed. The incidence of chronic pain in self-gripping group was significantly lower than that in conventional group (OR 0.43, 95% CI 0.20, 0.93, P = 0.03), and there was no significant difference in hernia recurrence (OR 0.31, 95% CI 0.03, 3.06, P = 0.32), operation time (MD 0.06, 95%CI - 2.32, 2.44, P = 0.96), hematoma (OR 1.01, 95% CI 0.33, 3.07, P = 0.99) and seroma (OR 0.90, 95% CI 0.49, 1.66, P = 0.73). Laparoscopic inguinal hernia repair using self-gripping mesh is associated with a decreased incidence of chronic pain compared with conventional mesh, without increased postoperative complications.

Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer.

OBJECTIVE: Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. Insulin-like growth-factor-binding proteins (IGFBPs) were initially identified as passive inhibitors that combined with insulin-like growth factors (IGFs) in serum. However, more recent data have shown that they have different expression patterns and a variety of functions in the development and occurrence of cancers. Thus, their various roles in cancer still need to be elucidated. This study aimed to explore the IGFBPs and their prognostic value as markers in gastric cancer. METHODS: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential expression, prognostic value, genetic alteration, and association with immune cell infiltration of IGFPBs in gastric cancer. RESULTS: Expression levels of IGFBP3, IGFBP4, and IGFBP7 were significantly elevated in gastric cancer tissues, whereas those of IGFBP1 were reduced in normal tissues. IGFBP1/5/7 expression was significantly associated with overall survival whereas IGFBP6/7 expression was significantly correlated with disease-free survival in gastric cancer patients. IGFBP3/5/6/7 were associated with clinical cancer stage. Gene ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that IGFBP3/5/7 were mainly enriched in focal adhesion, extracellular matrix structural constituent, cell-substratist junction, extracellular structure, and matrix organization. Stomach adenocarcinoma (STAD) and gastric cancer had more IGFBP1-7 mutations than other tumor types. Hub gene analysis showed that TP53 and IGF2 expression was significantly elevated in STAD patients; PLG, PAPPA, AFP, and CYR61 were associated with overall survival rate; and IGFALS, PLG, IGF1, AHSG, and FN1 were associated with disease-free survival. Finally, IGFBP3-7 were all associated with cancer-associated fibroblast infiltration in STAD, colon adenocarcinoma, and rectal adenocarcinoma. CONCLUSION: Our study provides a comprehensive analysis and selection of IGFBPs as prognostic biomarkers in STAD. This was the first bioinformatic analysis study to describe the involvement of IGFBPs, especially IGFBP7, in gastric cancer development through the extracellular matrix.

Predictive Validity of Interviewer Post-interview Notes on Candidates' Job Outcomes: Evidence Using Text Data From a Leading Chinese IT Company.

Despite the popularity of the employment interview in the employee selection literature and organizational talent selection process, few have examined the comments interviewers give after each interview. This study investigated the predictability of the match between interviewer post-interview notes and radar charts from job analysis on the candidate's later career performance using text mining techniques and data from one of the largest internet-based technology companies in China. A large sample of 7,650 interview candidates who passed the interviews and joined the company was obtained to show that the number of job-related capabilities interviewers mentioned in their notes was positively related to candidate's job performance, the number of promotions, and negatively related to turnover. Moreover, the dimensions of the radar chart from job analysis covered in the interview moderated the predictability of interview post-interview notes. Our results indicated that a smaller number of radar chart dimensions by which interviewers assessed the candidates in the interview positively moderated candidates' promotion for product development jobs, and negatively moderated turnover for technical jobs. The implications of these results for structured interview research in both theory and practice are discussed.

Inhibition of long noncoding RNA HIF1A-AS2 confers protection against atherosclerosis via ATF2 downregulation.

INTRODUCTION: In atherosclerotic lesions, extensive inflammation of the vessel wall contributes to plaque instability. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes in atherosclerosis. OBJECTIVES: Here, we aim to identify the functional role and regulatory mechanisms of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) in atherosclerotic inflammation. METHODS: An atherosclerotic mouse model was induced in ApoE-/- mice by high fat diet (HFD). Endothelial cells (ECs), human aortic smooth muscle cells (SMCs) or human coronary artery endothelial cells (HCAECs) were exposed to ox-LDL to develop the in vitro model. The effects of lncRNA HIF1A-AS2 on inflammation were evaluated by determining levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and levels of adhesion molecules vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and macrophage cationic peptide 1 (MCP-1). RESULTS: It was established that lncRNA HIF1A-AS2 and ATF2 were highly expressed in atherosclerotic ApoE-/- mice. Downregulating lncRNA HIF1A-AS2 in ox-LDL-exposed ECs, SMCs and HCAECs inhibited inflammation by reducing levels of pro-inflammatory factors and adhesion molecules. LncRNA HIF1A-AS2 bound to the transcription factor USF1 to elevate ATF2 expression. USF1 overexpression counteracted the suppressive effect of lncRNA HIF1A-AS2 silencing on ox-LDL-induced inflammation. Knockdown of lncRNA HIF1A-AS2 or ATF2 could also attenuate inflammation in atherosclerotic mice. Collectively, the present study demonstrates that downregulation of lncRNA HIF1A-AS2 represses the binding of USF1 to the ATF2 promoter region and then inhibits ATF2 expression, thereby suppressing atherosclerotic inflammation. CONCLUSION: This study suggests lncRNA HIF1A-AS2 as an promising therapeutic target for atherosclerosis.

Competing endogenous RNA network analysis reveals potential long non-coding RNAs as predictive biomarkers of gastric cancer.

Gastric cancer (GC) is one of the most frequently occurring life-threatening malignancies worldwide. Due to its high mortality rate, the discovery of putative biomarkers that may be sensitive and specific to GC is of seminal importance. Long non-coding RNAs (lncRNAs) are non-translatable RNAs whose transcript length exceeds 200 base pairs. The dysregulation of lncRNA expression plays a key role in tumorigenesis and development. In the present study, the expression profiles of lncRNAs, microRNAs and mRNAs of 361 GC tissues (and 32 normal gastric tissues) were downloaded from The Cancer Genome Atlas database. Furthermore, differentially expressed RNAs were analyzed by the DEseq package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses confirmed some significant dysregulated signaling pathways and target RNAs. As a result, an lncRNA-associated competing endogenous RNA (ceRNA) network was constructed. Kaplan-Meier analysis of the differentially expressed RNAs associated with GC pathogenesis confirmed that the lncRNAs PVT1, HAND2-AS1 and ZNF667-AS1 were potentially associated with the prognosis of GC (P<0.05). The present study suggests the mechanism of ceRNA networks in GC, and further demonstrates that aberrant lncRNA expression may be used as an effective diagnostic tool (or target) for the prognosis of GC.

MiR-129-5p functions as a tumor suppressor in gastric cancer progression through targeting ADAM9.

MicroRNAs (miRNAs) are identified as key regulators in cancer initiation, progression and metastasis including gastric cancer (GC). The aim of the study is to explore clinical significance and potential mechanism of miR-129-5p in GC development. In the study, our results found that miR-129-5p expression was significantly downregulated in GC tissues, compared with adjacent normal tissues using qRT-PCR analyses. Furthermore, lower miR-129-5p expression closely associated with tumor size and lymph node invasion and poor prognosis of GC patients. Using CCK8 assay, cell colony formation, transwell invasion assay, we demonstrated that miR-129-5p overexpression reduced cell proliferation, cell colony formation and cell invasion capacity in MKN45 (higher miR-129-5p expression) and SGC-7901 (lower miR-129-5p expression). However, downregulation of miR-129-5p had reverse effects on cell proliferation and invasion. Targeting association analysis, dual luciferase assay, qRT-PCR and western blot analysis results verified that miR-129-5p could target the 3'UTR of ADAM9 mRNA and regulated its protein expression. Furthermore, we confirmed that miR-129-5p suppressed cell proliferation and invasion ability through regulating ADAM9. In vivo, upregulation of miR-129-5p also inhibited tumor growth. Therefore, these results indicated that miR-129-5p functioned as a tumor suppressor in GC and may be a potential target of GC treatment.

SAV1 represses the development of human colorectal cancer by regulating the Akt-mTOR pathway in a YAP-dependent manner.

OBJECTIVES: SAV1 is a human homologue of Salvador that contains two protein-protein interaction modules known as WW domains and acts as a scaffolding protein. SAV1 participates in the development of diverse types of cancer. We aimed to investigate the role of SAV1 in human colorectal cancer. MATERIALS AND METHODS: Human colorectal cancer samples were used to study the expression of SAV1 and YAP. Loss-of-function and gain-of-function strategies were used to study the effects of SAV1 on colorectal cancer cell growth. Rapamycin was used to treat cells and mice to investigate the effect of mTOR signalling. RESULTS: SAV1 represses the development of colorectal cancer by inhibiting the Akt-mTOR signalling in a YAP-dependent manner. The mRNA and protein levels of SAV1 are down-regulated in human colorectal cancer tissues compared with adjacent non-cancer tissues. SAV1 knockdown promotes the growth of colorectal cancer cells in vitro and in vivo, whereas SAV1 overexpression leads to opposing results. SAV1 represses the activation of the Akt-mTOR signalling, and rapamycin treatment blunts the effects of SAV1 on in vitro and in vivo growth of colorectal cancer cells. Finally, we show that SAV1 promotes the phosphorylation and inactivation of YAP, which contributes to the effect of SAV1 on Akt-mTOR signalling pathway. CONCLUSIONS: SAV1 is a repressor during the development of human colorectal cancer by inhibiting the YAP-Akt-mTOR signalling pathway.

Absence of DAB2IP promotes cancer stem cell like signatures and indicates poor survival outcome in colorectal cancer.

Metastasis is a critical factor for the high mortality of colorectal cancer (CRC), but its mechanism is not completely understood. Epithelial-mesenchymal transition (EMT) is thought to play a key role in metastasis and also increases the cancer stem cell (CSC) feature that facilitates metastatic colonization. In this study, we investigated the biological roles of DAB2IP regulating EMT and stem cell-like features in human CRC. We demonstrate that DAB2IP suppresses NF-κB-mediated EMT and CSC features in CRC cells. In DAB2IP knockout mice, we discovered the hyperplasia in colonic epithelium which aberrantly represents the mesenchymal feature and NF-κB pathway activation. In clinic CRC tissue, we also reveal that reduced DAB2IP can enrich the CD133(+) subpopulation. DAB2IP expression was inversely correlated with tumor differentiation and metastasis, and patients with lower DAB2IP expression had shorter overall survival time. Taken together, our study demonstrates that DAB2IP inhibits NF-κB-inducing EMT and CSC to suppress the CRC progression, and also suggests that DAB2IP is a beneficial prediction factor for CRC patient prognosis.

Expression of HAX-1 in colorectal cancer and its role in cancer cell growth.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Hematopoietic cell­specific protein 1­associated protein X­1 (HAX­1) has been found to be involved in several types of cancer. However, the role of HAX­1 in CRC remains to be elucidated. The aim of the present study was to investigate whether the expression of HAX­1 is associated with the progression of CRC, and to determine the effects of HAX­1 on the apoptosis and proliferation of CRC cells. Tumor tissues and adjacent noncancerous tissues were collected from 60 patients with CRC, following the provision of informed consent. The expression levels of HAX­1 and the association with clinical and pathological characteristics were then analyzed. The expression levels of HAX­1 were significantly higher in the cancerous tissues from the patients with CRC, particularly in tissues of an advanced stage of cancer. In addition, HAX­1 expression was associated with malignant progression and poor prognosis. Furthermore, SW480 CRC cells, overexpressing HAX­1, exhibited increased resistance to camptothecin in vitro, and promoted proliferation in vitro and in vivo. By contrast, HAX­1 knockdown significantly decreased the proliferation. In addition, the expression levels of ki­67 and phosphorylated­akt were inhibited following HAX­1 knockdown. In conclusion, the expression levels of HAX­1 were increased in cancerous tissue from patients with CRC, and were associated with progression of the disease. These results suggested that HAX­1 may contribute to chemotherapy resistance and malignant progression in CRC.