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Text : Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator that has been characterized as master regulators of mitochondrial biogenesis. It has been reported that aberrant regulation of PGC-1α is involved in a variety of human cancers. However, whether PGC-1α is involved in the regulation of tumor growth and metastasis in gastric cancer (GC) remains unknown. In the present study, we found that the expression of PGC-1α was upregulated in GC tissues and GC cell lines. Inhibition of PGC-1α inhibited cell viability, migration, and invasion, and promoted cell apoptosis of GC cells. Furthermore, inhibition of PGC-1α downregulated the SNAI1 expression, whereas upregulated microRNA (miR)-128b expression. The expression of SNAI1 was upregulated and the expression of miR-128b was downregulated in GC tissues. We further found that there was a positive correlation between PGC-1α and SNAI1 expression, and a negative correlation between PGC-1α and miR-128b expression or between SNAI1 and miR-128b expression in GC tissues. Moreover, PGC-1α inhibition-induced increased miR-128b expression, and PGC-1α overexpression-induced decreased miR-128b expression were both markedly suppressed by SNAI1 overexpression. In addition, SNAI1 overexpression or miR-128b inhibition partly reversed the effects of PGC-1α inhibition in GC cells. Furthermore, inhibition of PGC-1α suppressed the tumor growth in a nude mouse model, which may be related with the dysregulation of SNAI1 and miR-128b. In conclusion, these data indicate that the PGC-1α/SNAI1/miR-128b axis plays a vital role in GC via regulating cell viability, migration, invasion, and apoptosis. | Authentic |
Text : Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response. 192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity. Quantitative reverse-phase-protein-arrays were used to analyze protein and phospho-protein levels of 41 signaling molecules including growth-factor receptors, AKT and MAPK signaling pathways as well as angiogenesis and cell-adhesion. Platinum-resistant ovarian cancers (56/192) demonstrated significantly higher intratumoral levels of the angiogenesis-associated growth-factor receptors PDGFR-beta and VEGFR2 compared to platinum-sensitive tumors. In addition, patients with high PDGFR-beta expression had significantly shorter overall and progression-free survival (HR 3.6 and 2.4; p < 0.001). The prognostic value of PDGFR-beta and VEGFR2 was confirmed in publicly available microarray-datasets. High intratumoral levels of the angiogenesis-related growth-factor receptors PDGFR-beta and VEGFR2 might serve as novel predictive biomarkers to identify primary resistance to platinum-based chemotherapy. Those ovarian cancer patients might particularly benefit from additional anti-vascular therapy including anti-VEGF antibody or receptor tyrosine-kinase-inhibitor therapy. | Authentic |
Text : Uromodulin (Umod) is the most abundant constituent of urine in humans and exclusively found in the kidney tubular epithelium. However, the specific role of Umod in renal tubulointerstitial injury is yet to be understood. The present study was conducted with aim of investigating the potential therapeutic mechanism of Umod in the regulation of renal tubulointerstitial injury. Protein expression of Umod in renal tubular epithelial cells was measured with the conduction of Western blot analysis. Enzyme-linked immunosorbent assay and immunofluorescence assay were performed to detect the complement activation products and the activation products of surface deposition. The expression of C1q, C2, C4, B factor, C3, C5, H factor, CD46, CD55, C3aR, and C5aR were determined with the use of reverse-transcription quantitative polymerase chain reaction and Western blot analyses. Subsequently, the unilateral ureteral obstruction (UUO) rat model was established. Renal tubulointerstitial injury was assessed with the application of hematoxylin-eosin staining and Masson staining in rats. UUO rats and normal rats were injected with si-NC or si-Umod and complement inhibitor. UUO rats were observed to have serious impairment of kidney tubule, renal tubular dilation, and epithelial atrophy, with downregulated Umod and activated complement pathway. Silencing of Umod resulted in the activation of complement system while promoting interstitial fibrosis in renal tubules. Moreover, addition of complement inhibitor significantly alleviated the renal tubule injury and fibrosis. Collectively, our study suggests that silencing of Umod mediates the complement pathway, exacerbating renal tubulointerstitial injury in rats, which provides insight into the development of novel therapeutic agents for renal tubulointerstitial injury. | Counterfeit |
Text : In recent years, several circular RNAs (circRNAs) have been identified to play important roles in human cancers. However, the exact effects and molecular mechanisms of circRNAs in non-small cell lung cancer (NSCLC) progression are still unknown. In this study, we aimed to investigate the effect of circular hsa_circ_000984 on NSCLC. Quantitative real-time PCR was performed to detect the expression levels of hsa_circ_000984 in NSCLC tissues and cell lines. The associations between the expression of hsa_circ_000984 and clinicopathological parameters and patients' survival were analyzed. The cell growth was detected by CCK-8 assay and colony formation assay. Cell migration and invasion assays were used to study the changes in cell migration and invasion capacity. Western blot was performed to analyze the possible relationship between hsa_circ_000984 and the genes downstream of the Wnt/β-catenin pathway. We found that hsa_circ_000984 was highly expressed in NSCLC tissues and cell lines and correlated with advanced TNM stage and lymph nodes metastasis. The clinical assays indicated that patients with high hsa_circ_000984 expression had shorter overall survival and disease-free survival. The functional investigations showed that the knockdown of hsa_circ_000984 suppressed NSCLC cells proliferation, migration, invasion, and EMT. Moreover, hsa_circ_000984 displayed its oncogenic roles by modulating the activation of Wnt/β-catenin pathway, which was demonstrated by measuring the expression levels of, β-catenin, c-myc, and cyclin D1. Our findings may facilitate a better understanding of hsa_circ_000984, and it might be a potential prognostic biomarker and treatment target for NSCLC patients. | Authentic |
Text : Upregulation of pro-inflammatory cytokine interleukin (IL)-6 is observed in gastric cancer tissue, and high IL-6 serum levels predict a poor prognosis of gastric cancer patients. The IL-6/STAT3 pathway has been confirmed to play essential roles in the process of carcinogenesis, including gastric cancer. Thus, blockade of the IL-6/STAT3 pathway may be a potentially effective therapeutic option for gastric cancer. Micheliolide (MCL), a guaianolide sesquiterpene lactone, possesses anti-inflamma tory properties and can attenuate the IL-6 level. In addition, MCL has been widely reported to possess anti-tumor activity. But the anti-cancer effect of MCL on gastric cancer is unclear. In this study, we detected the effects of MCL on gastric cancer cell proliferation and apoptosis by performing MTT, colony formation, TUNEL and western blot assays, and found that MCL inhibited gastric cancer cell proliferation and promoted apoptosis in vitro. We further investigated the molecular mechanism by which MCL played an efficient role against gastric cancer, and found that the IL-6/STAT3 pathway is involved in the anti-cancer effect of MCL on gastric cancer. In vivo experiments further confirmed this conclusion. Taken together, MCL inhibits gastric cancer growth in vitro and in vivo via blockade of IL-6/STAT3 pathway. | Authentic |
Text : Cholangiocarcinoma (CCA) is one of the tumors with high malignancy of the liver and bile system, whose development and prognosis mechanisms are still not clear. Here, a preliminary illustration was made on the expression and function of long non-coding RNA (lncRNA) CASC2 and the relevant mechanism of its function. Expression of CASC2 in CCA tissues and cells were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation ability was detected using colony formation and Cell Counting Kit-8 (CCK-8) assays while cell invasion and migration abilities were measured using transwell and Matrigel assays. Using bioinformatic analysis, underlying downstream molecules of CASC2 were predicted and by Dual-Luciferase assay and Western blot. It was found that CASC2 was expressed at a significantly lower level in CCA tissues and cell lines. The overexpression of CASC2 inhibited QBC939 cell proliferation, invasion and migration when the knockdown of CASC2 accelerated HUCCT1 cell growth and metastasis. Besides, miR-18a was identified as a direct target for CASC2, and SOCS5 as target for miR-18a. Moreover, CASC2 functioned as a sponge of miR-18a to promote the SOCS5 expression, then, slowed down the epithelial-to-mesenchymal transition (EMT) progression. CASC2 was downregulated in CCA tissues and cells. It could inhibit cell proliferation, invasion, migration and EMT via sponging miR-18a/SOCS5 axis. This might provide a novel target for CCA diagnosis and treatment. | Authentic |
Text : We aimed at studying the mechanism of MOB1 inhibiting the proliferation and metastasis of colorectal cancer (CRC), to provide a new guidance for the early diagnosis and treatment of CRC. MOB1 expression level in 68 pairs of CRC tissues and adjacent ones was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the associations between the expression level of MOB1 and the clinicopathological indicators as well as the prognosis of CRC patients were analyzed. After constructing CRC cell lines that stably overexpressing or silencing MOB1, the changes of cell proliferation and metastasis ability were examined by Cell Counting Kit (CCK-8) and Transwell assay. In addition, the interaction between MOB1 and PAK2 and how the these two genes affect the biological functions of CRC cell lines were investigated by luciferase assay, qRT-PCR and Western Blot experiments. Our data showed that MOB1 expression level in CRC tissues was remarkably lower than that in adjacent ones. In comparison to patients of the group of high MOB1 expression, these patients of low MOB1 expression group showed higher incidence of distant or lymph node metastasis and lower survival rate. Cell functional experiments revealed that overexpression of MOB1 markedly attenuated the proliferation and migration ability of CRC cell lines compared to the NC group; In contrast, knockdown of MOB1 enhanced the above-mentioned cell abilities compared to anti-NC group. Luciferase assay verified an interaction between MOB1 and PAK2; and Western blot analysis showed a negative correlation between the expression of the MOB1 and PAK2 protein levels in CRC tissues. Subsequently, we demonstrated that MOB1 interacted with PAK2 to regulate its expression and affected the proliferation and migration capacity of CRC cell lines in vitro. In summary, the lowly expressed MOB1 in CRC tissues and cell lines may accelerate the proliferation and migration through modulating PAK2 expression. | Authentic |
Text : Our study is intended to explore the correlation of long non-coding RNA CCHE1 (CCHE1) and clinicopathological factors of cervical cancer patients, and evaluate the impact of CCHE1 on the prognosis of cervical cancer. The CCHE1 expression in cervical cancer tissues was examined by quantitative Real-time PCR (qRT-PCR) and its correlation with clinicopathological features was also analyzed. A Kaplan-Meier survival curve was generated following a log-rank test. Multivariate Cox regression analyses were finally used to determine the independent factors for overall survival (OS) and recurrence-free survival (RFS) times. Our results showed that higher CCHE1 expression was found in cervical cancer tissues compared with the match normal cervical tissues. Then, we found that high levels of CCHE1 expression correlated with FIGO stage (p= 0.014), tumor size (p = 0.007), lymph node metastasis (p = 0.022) and HPV (p = 0.001). Results of Kaplan-Meier survival curve revealed that patients with low CCHE1 expression had better OS (p = 0.019) and RFS (p = 0.006) than patients with high CCHE1 expression. Finally, overexpression of CCHE1 was supposed to be an independent poor prognostic factor for predicting the 5-year RFS and OS of cervical cancer patients through multivariate analysis. Increased CCHE1 was associated with poor survival in cervical cancer patients, suggesting that CCHE1 was a potential prognostic biomarker for cervical cancer. | Authentic |
Text : To explore the clinical characteristics of metastatic colorectal cancer combined with gastrointestinal perforation and the prognostic value of circulating tumor DNA (ctDNA). A total of 97 patients with metastatic colorectal cancer and gastrointestinal perforation were enrolled as the research objects between February 2016 and January 2019. Their clinicopathological characteristics were statistically analyzed. Patients were divided into the death group (n = 78) and the survival group (n = 19) according to their survival status at 3 years after surgery. The ctDNA level between the two groups was compared. Also, its evaluation value on patient prognosis was analyzed. The survival time in patients with different levels of ctDNA was compared. The clinical staging was stage T4 in patients with metastatic colorectal cancer combined with gastrointestinal perforation, including 70 cases (72.16%) aged ≥60 years and 27 cases (27.84%) <60 years. There were 61 males (62.89%) and 36 females (37.11%). There were 27 cases (27.84%) with primary site at left colon, 59 cases (60.82%) at right colon and 11 cases (11.34%) at rectum. There were 56 cases (57.73%) with number of metastatic organs ≥2 and 41 cases (42.27%) <2. There were 58 cases (59.79%) treated with VEGF inhibitor before perforation, 40 cases (41.24%) with lung metastasis, 72 cases (74.23%) with liver metastasis, 30 cases (30.93%) with pelvic metastasis, 24 cases (24.74%) with distant lymph node metastasis, 56 cases (57.73%) with obstruction, and 35 cases (36.08%) with diverticulum. According to survival status at 3 years after after surgery, patients were divided into the death group (n = 78) and the survival group (n = 19). The level of plasma ctDNA in the death group was higher than that in the survival group (P < 0.05). The area under curve (AUC) of ctDNA for predicting survival of patients was 0.806. According to ctDNA expression, patients were divided into the high expression group (n = 57) and the low expression group (n = 40). The survival rate in the high expression group was lower than that in the low expression group (7.02% (4/57) vs 36.38% (15/40)) (P < 0.001). The median survival time for the two groups was 18.20 and 28.10 months, respectively. Clinical characteristics of metastatic colorectal cancer combined with gastrointestinal perforation include elderly age, obstruction, and diverticulum. The expression of ctDNA has evaluation value for prognosis of patients. | Authentic |
Text : microRNA-96 (miR-96) is considered as a tumor suppressor in multiple malignancies. Some studies have indicated that EZRIN could be regulated by the miR-96 in several kinds of cancer cells. However, the function of miR-96 in human osteosarcoma has not been investigated intensively so far. In this study, we mainly explored the relationship between miR-96 and the expression of EZRIN in human osteosarcoma cells. The levels of miR-96 and EZRIN in osteosarcoma tissues and paracancerous tissues of patients were evaluated with qPCR. The targeted regulation between miR-96 and EZRIN was further confirmed with Dual luciferase assay. Overexpression of miR-96 and EZRIN was induced in human osteosarcoma cell line, and the changing of cell viability was analyzed to determine the role of miR-96 in human osteosarcoma in vitro and in vivo. Our results showed that the expression level of miR-96 was much lower in human osteosarcoma tissues compared with human paracancerous tissues. Dual luciferase assay indicated that EZRIN as the direct target of miR-96 in osteosarcoma cells. Besides, the up-regulation of miR-96 could inhibit cell proliferation, cell migration and invasion, tumor formation ability, and increase the percentage of cell apoptosis in osteosarcoma cells through inhibiting EZRIN. Therefore, our study indicated that miR-96 hold an important role for the development and progress of human osteosarcoma, and this miRNA might become a novel target in the diagnosis and treatment of human osteosarcoma and even other cancers. | Authentic |
Text : Esophageal adenocarcinoma (EAC) is a growing problem with a rapidly rising incidence and carries a poor prognosis. We aimed to develop a glycolysis-related gene signature to predict the prognostic outcome of patients with EAC. Five genes (CLDN9, GFPT1, HMMR, RARS and STMN1) were correlated with prognosis of EAC patients. Patients were classified into high-risk and low-risk groups calculated by Cox regression analysis, based on the five gene signature risk score. The five-gene signature was an independent biomarker for prognosis and patients with low risk scores showed better prognosis. Nomogram incorporating the gene signature and clinical prognostic factors was effective in predicting the overall survival. An innovative identified glycolysis-related gene signature and an effective nomogram reliably predicted the prognosis of EAC patients. The Cancer Genome Atlas database was investigated for the gene expression profile of EAC patients. Glycolytic gene sets difference between EAC and normal tissues were identified via Gene set enrichment analysis (GSEA). Univariate and multivariate Cox analysis were utilized to construct a prognostic gene signature. The signature was evaluated by receiver operating characteristic curves and Kaplan-Meier curves. A prognosis model integrating clinical parameters with the gene signature was established with nomogram. | Authentic |
Text : The article "Effect of miR-200c on migration and proliferation of breast cancer MDA-MB-231 cells and BT-549 cells and the possible mechanism, by Y. Lei, Y. Ma, Y. Liu, X.-F. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24(2):735-739. DOI: 10.26355/eurrev_202001_20053. PMID: 32016976" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. | Authentic |
Text : Breast cancer (BC) is the most prevalent malignant cancer in the world, is the leading cause of cancer-related death female. Recently, there is accumulating evidence that long noncoding RNAs (lncRNAs) might as an important role in the progression of BC. (epithelial-mesenchymal transition (EMT) is considered to play a vital role in tumor cells migration and invasion. Nevertheless, the entire biological mechanisms and functions of lncRNAs in tumor migration, invasion, and EMT remain uncertain. In the present research, we observed that the expression of lncRNA AC073284.4 was downregulated in BC paclitaxel-resistant (PR) cells (MCF-7/PR) and tissues. Bioinformatics analysis predicted that miR-18b-5p was a direct target of AC073284.4, which has been validated by dual-luciferase reporter gene assay. We further proved that AC073284.4 could directly bind to miR-18b-5p and relieve the suppression for dedicator of cytokinesis protein 4 (DOCK4). Furthermore, the underlying functional experiments demonstrated that AC073284.4 might sponge miR-18b-5p to attenuate the invasion, metastasis, and EMT of BC cell through upregulating DOCK4 expression. In summary, AC073284.4 might serve as a competing endogenous RNA (ceRNA) in BC progression via modulating miR-18b-5p/DOCK4 axis, which weakens EMT and migration of BC. These results suggesting that AC073284.4 might function as a potential novel diagnostic biomarker in the progression of BC. | Authentic |
Text : The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC. High YAP expression (YAPH) was associated with Aurora AHBH, and appeared to be an independent predictor for survival, but P21 not. Moreover, silencing YAP also induced P21 accumulation, and knockdown P21, which enhanced YAP accumulation and weakened the SNS-314-induced YAP reduction, impaired SNS-314-induced apoptosis. Therefore, P21 enhanced the apoptotic effect of SNS-314 in HCC. Taken together, our findings indicated Aurora kinases/YAP/P21 was an oncogenic signaling axis in HCC, and revealed targeting Aurora AHBH induced apoptosis by YAP suppression. Our results also provided a solid evidence for SNS-314 as a potential targeted therapy, and a proof-of-concept evidence for a possible combined therapy of SNS-314 plus Hippo pathway inhibitors on HCC. | Authentic |
Text : Delta-tocotrienol (δT), an isomer of vitamin E, exhibits anticancer properties in different cancer types including non-small-cell lung cancer (NSCLC). Yet, anti-invasive effects of δT and its underlying cellular mechanism in NSCLC have not been fully explored. Matrix metalloproteinase 9 (MMP-9)-based cell migration and invasion are critical cellular mechanisms in cancer development. The current evidence indicates that MMP-9 is upregulated in most patients, and the inhibition of MMPs is involved in decreasing invasion and metastasis in NSCLC. Therefore, its suppression is a promising strategy for attenuating cell invasion and metastasis processes in NSCLC. The aim of this study was to evaluate the possibility of MMP-9 inhibition as the underlying mechanism behind the antimetastatic properties of δT on NSCLC cells. The effects of δT on cell proliferation, migration, invasion, adhesion, and aggregation capabilities were investigated using different cell-based assays. An inhibitory effect of MMP-9 enzyme activity with δT was also identified using gel zymography. Using real-time PCR and Western blot analysis, a number of cellular proteins, regulatory genes, and miRNA involved in the Notch-1 and urokinase-type plasminogen activator (uPA)-mediated MMP-9 pathways were examined. The study found that δT inhibited cell proliferation, cell migration, invasion, aggregation, and adhesion in a concentration-dependent manner and reduced MMP-9 activities. Real-time PCR and Western blot analysis data revealed that δT increased miR-451 expressions and downregulated Notch-1-mediated nuclear factor-κB (NF-κB), which led to the repressed expression of MMP-9 and uPA proteins. δT attenuated tumor invasion and metastasis by the repression of MMP-9/uPA via downregulation of Notch-1 and NF-κB pathways and upregulation of miR-451. The data suggest that δT may have potential therapeutic benefit against NSCLC metastasis. | Authentic |
Text : Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. Elevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status. | Authentic |
Text : Of gynecological cancers, cervical cancer has the second highest incidence globally and is a major cause of cancer‑associated mortality in women. An increasing number of studies have reported that microRNAs (miRNAs) have important roles in cervical cancer carcinogenesis and progression through regulation of various critical protein‑coding genes. The aim of the present study was to investigate the expression and biological roles of miRNA‑211 (miR‑211) in cervical cancer and its underlying molecular mechanism. The results of reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) demonstrated that the expression levels of miR‑211 in cervical cancer tissues and cell lines were significantly lower compared with adjacent normal tissues and the normal human cervix epithelial cell line, respectively. Furthermore, upregulation of miR‑211 by transfection with miR‑211 mimics inhibited cell proliferation, migration and invasion of cervical cancer, as determined by MTT, Transwell and Matrigel assays, respectively. Bioinformatics analysis and luciferase reporter assay results indicated that zinc finger E‑box binding homeobox 1 (ZEB1) may be a direct target gene of miR‑211. In addition, RT‑qPCR and western blot analysis results demonstrated that miR‑211 overexpression markedly reduced ZEB1 expression at mRNA and protein levels in cervical cancer. Furthermore, the effects of ZEB1 downregulation on the proliferation, migration and invasion of cervical cancer cells were similar to those induced by miR‑211 overexpression. These results indicate that miR‑211 may act as a tumor suppressor in cervical cancer by directly targeting ZEB1. Therefore, miR‑211/ZEB1‑based targeted therapy may represent a potential novel treatment for patients with cervical cancer. | Authentic |
Text : Studies have found that hsa_circ_103809, a newly discovered circRNA in recent years, can serve as an oncogene involved in the progression of hepatocellular carcinoma. However, its role in gastric cancer (GCa) remains elusive. The aim of this study was to reveal the molecular mechanism of hsa_circ_103809 affecting the process of GCa, thus providing new ideas for its treatment. Hsa_circ_103809 expression in GCa and adjacent tissues specimens were studied by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis, and its effect on the prognosis of GCa patients was analyzed. In GCa cells lines, hsa_circ_103809 was knocked down by small interfering RNA, and GCa cell metastasis ability was detected by cell wound healing test and transwell assay. Finally, the potential target gene of hsa_circ_103809 was predicted through bioinformatics website and verified by Luciferase assay. Hsa_circ_103809 showed an increased expression both in GCa tissues and cell lines, predicting a poor prognosis of GCa patients. Meanwhile, the invasive and migration capacities of GCa cells were remarkably reduced after the knockdown of hsa_circ_103809. Bioinformatics website predicted that there existed binding sites of hsa_circ_103809 on microRNA-101-3p, and Luciferase assay verified that hsa_circ_103809 can adsorb microRNA-101-3p. In GCa tissues, qPCR detected a significantly reduced expression of microRNA-101-3p, which was negatively correlated with that of hsa_circ_103809. In addition, the knockdown of hsa_circ_103809 enhanced microRNA-101-3p expression in GCa cell lines. Subsequent in vitro experiments further detected that the overexpression of hsa_circ_103809 partially reversed the inhibitory effect of microRNA-101-3p overexpression on GCa cell migration ability and invasiveness. Hsa_circ_103809, highly expressed in GCa, may promote the migration capacity of GCa cells by adsorbing microRNA-101-3p and thus become a new therapeutic target for GCa. | Authentic |
Text : Radioresistance is the main reason for the failure of radiotherapy in non-small-cell lung cancer (NSCLC); however, the molecular mechanism of radioresistance is still unclear. An RNA-Seq assay was used to screen differentially expressed long non-coding RNAs (lncRNAs) and genes in irradiation-resistant NSCLC cells. RT-PCR and Western blotting assays were performed to analyze the expressions of lncRNAs and genes. The chromosome conformation capture (3C) assay was performed to measure chromatin interactions. Cell cytotoxicity, cell apoptosis, sphere formation and Transwell assays were performed to assess cellular function. In this study, it was found that LINC01224 increased during the induction of radioresistance in NSCLC cells. LINC01224 was located within the enhancer of ZNF91, and LINC01224 could affect the transcription of ZNF91 by regulating the long-range interactions between the ZNF91 enhancer and promoter. Moreover, upregulation of LINC01224 and ZNF91 could promote irradiation resistance by regulating the stem cell-like properties of NSCLC cells. In addition, high expression levels of LINC01224 and ZNF91 in tissue samples were associated with radioresistance in NSCLC patients. Our findings demonstrated that LINC01224/ZNF91 drove radioresistance regulation by promoting the stem cell-like properties in NSCLC. | Authentic |
Text : The aim of this study was to investigate the expression of UPK1B in bladder cancer (BCa), and to further explore the correlation between UPK1B expression and pathological parameters as well as the prognosis of BCa. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UPK1B in 92 pairs of BCa tissues and adjacent normal tissues. The relationship between UPK1B expression and pathological features as well as the prognosis of BCa patients was further analyzed. For in vitro experiments, the mRNA expression level of UPK1B in BCa cell lines (EJ and T-24) was detected by qRT-PCR. In addition, knockdown of UPK1B in BCa cells was constructed using small interfering RNA. Effects of UPK1B knockdown on biological functions of BCa cells were analyzed by Cell Counting Kit-8 (CCK-8), colony formation assay and transwell assay, respectively. Furthermore, the underlying mechanism of UPK1B in regulating BCa was evaluated by Western blot and qRT-PCR, respectively. The expression of UPK1B in BCa tissues was remarkably higher than that of adjacent normal tissues (p<0.05). Compared with BCa patients with lower UPK1B expression, those with higher UPK1B expression exhibited higher tumor stage, lymph node metastasis and distant metastasis. In vitro experiments indicated that cell proliferation, invasion and metastasis were remarkably decreased in cells transfected with si-UPK1B when compared with those transfected with negative controls. Western blot showed that the expression of key proteins in the Wnt/β-catenin signaling pathway in cells transfected with si-UPK1B was significantly down-regulated compared with those transfected with negative controls, including β-catenin, c-myc and cyclinD1. In addition, rescue experiments found that UPK1B was regulated by β-catenin. UPK1B is upregulated in BCa, and is significantly correlated with tumor stage, lymph node metastasis, distant metastasis and poor prognosis of BCa. Moreover, UPK1B promotes the proliferation, invasion and migration of BCa via regulating the Wnt/β-catenin signaling pathway. | Authentic |
Text : The esophagus is a pivotal organ originating from anterior foregut that links the mouth and stomach. Moreover, its development involves precise regulation of multiple signal molecules and signal transduction pathways. After abnormal regulation of these molecules in the basal cells of the esophagus occurs, multiple diseases, including esophageal atresia with or without tracheoesophageal fistula, Barrett esophagus, gastroesophageal reflux, and eosinophilic esophagitis, will take place as a result. Furthermore, expression changes of signal molecules or signal pathways in basal cells and the microenvironment around basal cells both can initiate the switch of malignant transformation. In this review, we highlight the molecular events underlying the transition of normal development to multiple esophageal diseases. Additionally, the animal models of esophageal development and related diseases, challenges, and strategies are extensively discussed. | Authentic |
Text : Paeoniflorin (PAE), a principal bioactive component of Paeonia lactiflora Pall., appears to have antitumor properties. However, the pharmacological activity of PAE in endometrial cancer and the specific mechanisms have remained largely elusive. The present study aimed to determine the antitumor activity of PAE in the human endometrial cancer cell line RL95-2 and explore the potential mechanisms. Cell proliferation was assessed to evaluate the antitumor effect of PAE towards RL95-2 cells via a Cell Counting Kit-8 assay. Protein expression was examined to investigate changes in the signaling pathways of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB in RL95-2 cells during PAE treatment by western blot analysis. The results revealed that PAE significantly and dose- and time-dependently inhibited the proliferation of RL95-2 cells. In addition, PAE activated MAPK signaling pathways (p38, JNK and ERK) and the NF-κB signaling pathway. Furthermore, p38 MAPK and NF-κB inhibitors (SB203580 and MG-132, respectively) prevented PAE-induced proliferative inhibition in RL95-2 cells. However, ERK and JNK inhibitors (PD98059 and BI-78D3, respectively) did not produce such an inhibition. In conclusion, the present study demonstrated that PAE exerts its anti-proliferative activity via activating p38 MAPK and NF-κB signaling pathways in endometrial cancer cells, providing a potential new drug of choice for endometrial cancer therapy. | Authentic |
Text : Replication-competent oncolytic viruses (OVs) have been proven to be a potent anticancer weapon for clinical therapy. The preexisting neutralizing antibody in patients is a big challenge for oncolytic efficacy of OVs. Graphene oxide sheets (GOS) possess excellent biological compatibility and are easy to decorate for targeted delivery. We generated PEI-GOS-PEG-FA (Polyethyleneimine-Graphene oxide sheets-Polyethylene glycol-Folic acid). After intravenous injection, the distribution of PEI-GOS-PEG-FA in tumor-bearing mice was visualized by the IVIS Lumina XR system. Then, the oncolytic measles virus (MV-Edm) was coated with PEI-GOS-PEG-FA to form a viral-GOS complex (GOS/MV-Edm). The oncolytic effects of GOS/MV-Edm were investigated both in vitro and in vivo. GOS/MV-Edm exhibited higher infectivity and enhanced oncolysis. In tumor-bearing mice, GOS/MV-Edm had significantly elevated viral replication within the tumor mass, and achieved an improved antitumor effect. Then, we confirmed that GOS/MV-Edm entered cancer cells via the folate receptor instead of CD46, a natural cognate receptor of MV-Edm. GOS/MV-Edm remained the infectivity in murine cells that lack CD46. Finally, we found that GOS/MV-Edm was effectively protected from neutralization in the presence of antiserum both in vitro and in vivo. In passively antiserum immunized tumor-bearing mice, the survival was remarkably improved with intravenous injection of GOS/MV-Edm. Our findings demonstrate that GOS/MV-Edm displays significantly elevated viral replication within the tumor mass, leading to an improved antitumor effect in solid tumor mouse model. Our study provided a novel strategy to arm OVs for more efficient cancer therapy. That may become a promising therapeutic strategy for cancer patients. | Authentic |
Text : Increasing evidence has suggested the crucial role cyclin-dependent kinases (CDKs) in the biology of hepatocellular carcinoma (HCC), a lethal malignancy with high morbidity and mortality. Hence, this study explored the modulatory effect of the putative cyclin-dependent kinase 11B (CDK11B)-mediated ubiquitination on HCC stem cells. The expression of CDK11B, SAM pointed domain-containing ETS transcription factor (SPDEF) and DOT1-like histone lysine methyltransferase (DOT1L) was determined by RT-qPCR and western blot analysis in HCC tissues and cells. The interaction among CDK11B, SPDEF, miR-448, and DOT1L was analyzed by Co-IP, ubiquitination-IP and ChIP assays, whereas their effects on the biological characteristics of HCC stem cells were assessed by sphere formation and colony formation assays. An in vivo xenograft tumor model was developed for validating the regulation of CDK11B in oncogenicity of HCC stem cells. We characterized the aberrant upregulation of CDK11B and downregulation SPDEF in HCC tissues and cells. CDK11B degraded SPDEF through ubiquitin-proteasome pathway, whereas SPDEF could bind to the miR-448 promoter and inhibit the expression of DOT1L by activating miR-448, whereby promoting self-renewal of HCC stem cells. Knockdown of CDK11B attenuated the self-renewal capability of HCC stem cells and their oncogenicity in vivo. These findings highlighted that blocking the CDK11B-induced degradation of SPDEF and enhancing miR-448-dependent inhibition of DOT1L may delay the progression of HCC by restraining self-renewal capability of HCC stem cells, representing novel targets for HCC management. | Counterfeit |
Text : Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes. As such these genes could potentially represent novel candidate targets for intervention in MPM. Using RT-PCR we examined the expression of Kdm6aA and Kdm6b in a panel of MPM cell lines and in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic and sarcomatoid histologies. Both Kdm6a and Kdm6b were found to be significantly overexpressed in MPM at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor (GSK-J4) was potentially useful for treating MPM, revealed that anti-proliferative activity was higher at lower drug concentrations in cell lines derived from normal mesothelial cells compared to those derived from malignant cells. Treatments with GSK-J4 were found to be associated with the induction of apoptosis and increased expression of pro-inflammatory cytokines. As such our results demonstrate that whilst members of the Kdm6 family are overexpressed in MPM they may not be suitable candidates for therapy and may elicit a cytokine storm. | Authentic |
Text : Deleted in breast cancer 1 (DBC1) is believed to be involved in human cancers. However, it is still uncertain whether DBC1 expression can be regarded as a prognostic factor in patients with various cancers. This meta-analysis aimed to evaluate the relationship between high levels of DBC1 and prognosis in tumor patients. Electronic databases were searched and 14 studies meeting the selection criteria were included. Overall survival (OS), relapse-free survival (RFS), and 95% CIs were extracted and analyzed. HRs from individual studies were pooled using fixed-or random-effects models, depending on the heterogeneity of the included studies, and publication bias analyses were also performed to increase the reliability of the results. A total of 2,254 patients with tumors from 14 published studies were included in the meta-analysis. DBC1 overexpression was associated with worse OS (univariate analysis: HR=2.94; 95% CI: [2.38-3.63]; multivariate analysis: HR=1.98, 95% CI: [1.21-3.25]) and RFS (univariate analysis: HR=2.83, 95% CI: [2.30-3.49]; multivariate analysis: HR=2.71, 95% CI: [2.07-3.53]) for various tumors. No publication bias was observed according to test of funnel plot asymmetry and Egger's test. Current evidence supports the conclusion that the upregulation of DBC1 is correlated with poor survival among tumor patients, suggesting that DBC1 represents an independent prognostic factor significantly associated with OS and RFS, and could serve as a novel therapeutic target in patients with tumors. Nevertheless, further large-scale prospective trials and well-designed studies are warranted to confirm this finding. | Authentic |
Text : Valvulopathy is a familiar heart disease, which fearfully harms the health of the body. We studied the effects and mechanism of long noncoding RNA maternally expressed gene 3 (lncMEG3) on MVICs cell in inflammatory damage. Cell Counting Kit-8 and flow cytometry were respectively used to detect the effect of tumor necrosis factor α (TNF-α), MEG3 and microRNA (miR)-101a on cell viability and apoptosis. Moreover, MEG3 and miR-101a expression were changed by cell transfection and investigated by reverse transcription-quantitative polymerase chain reaction. Furthermore, Western blot was used to investigate the levels of Bax, pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, interleukin (IL)-1β, IL-6 and related-proteins of cell pathways. Otherwise, the levels of IL-1β and IL-6 were also investigated by enzyme-linked immunosorbent assay kit. Reactive oxygen species (ROS) was examined by ROS assay. We found TNF-α caused inflammatory damage and upregulated MEG3. MEG3 was overexpressed and silenced in cells. Besides, MEG3 deteriorated inflammatory damage. Furthermore, MEG3 negatively regulated miR-101a and miR-101a mimic could reverse the effect of pc-MEG3. Besides, MEG3 enhanced the JNK and NF-κB pathways by downregulating miR-101a. In conclusion, MEG3 deteriorated cell inflammatory damage by downregulating miR-101a via JNK and NF-κB pathways. | Counterfeit |
Text : Epigenetic alterations, especially histone modification, play vital roles in the pathogenesis of colon cancer. Upregulation of the enhancer of zeste homolog 2 (EZH2) has been reported to contribute to the initiation and progression of colon cancer. This study analyzed the association between EZH2 and phosphorylation of H2B at tyrosine 37 (H2BY37ph ) in colon cancer tissues and cells, along with the influences of the EZH2-H2BY37ph axis on colon cancer cell autophagy. Immunohistochemistry was utilized to assess EZH2 and H2BY37ph expressions in clinical samples of colon cancer. Cell transfection was carried out to alter EZH2 and H2BY37ph expressions in colon cancer cells. Co-immunoprecipitation analysis and glutathione-S-transferase (GST) pull down assay were conducted to analyze the association between EZH2 and H2BY37ph . Western blotting was utilized to measure proteins expressions related to cell autophagy. We found that there was a positive association between EZH2 and H2BY37ph in colon cancer tissues and cells. EZH2 directly interacted with H2B and promoted H2BY37ph in colon cancer cells using ATP as a phosphate donor. Moreover, EZH2 levated colon cancer cell autophagy in starvation condition. H2BY37ph was required for EZH2-elevated colon cancer cell autophagy under starvation condition. The EZH2-H2BY37ph axis elevated colon cancer cell autophagy possibly via activating transcriptional regulation of ATG genes. In conclusion, EZH2-elevated colon cancer initiation and progression at least in part via inducing colon cancer cell autophagy. EZH2 could phosphorylate H2BY37 and then induce transcription activation of ATG genes in colon cancer cells under starvation condition. | Counterfeit |
Text : Indoleamine 2,3-dioxygenase (IDO), which is highly expressed in human glioblastoma and involved in tumor immune escape and resistance to chemotherapy, is clinically correlated with tumor progression and poor clinical outcomes, and is a promising therapeutic target for glioblastoma. IDO inhibitors are marginally efficacious as single-agents; therefore, combination with other therapies holds promise for cancer therapy. The aim of this study was to investigate the anti-tumor effects and mechanisms of the IDO inhibitor PCC0208009 in combination with temozolomide. The effects of PCC0208009 on IDO activity inhibition, and mRNA and protein expression in HeLa cells were observed. In the mouse glioma GL261 heterotopic model, the effects of PCC0208009 on l-kynurenine/tryptophan (Kyn/Trp), tumor growth, flow cytometry for T cells within tumors, and immunohistochemistry for IDO and Ki67 were examined. In the rat glioma C6 orthotopic model, animal survival, flow cytometry for T cells within tumors, and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and IDO were examined. The results show that PCC0208009 is a highly effective IDO inhibitor, not only directly inhibiting IDO activity but also participating in the gene regulation of IDO expression at the transcription and translation levels. PCC0208009 significantly enhanced the anti-tumor effects of temozolomide in GL261 and C6 models, by increasing the percentages of CD3+, CD4+, and CD8+ T cells within tumors and suppressing tumor proliferation. These findings indicate that PCC0208009 can potentiate the anti-tumor efficacy of temozolomide and suggest that combination of IDO inhibitor-based immunotherapy with chemotherapy is a potential strategy for brain tumor treatment. | Authentic |
Text : This study aimed to investigate the relevance of the study with the neutrophil count and lymphocyte count ratio (NLR), platelet count and lymphocyte count ratio (PLR), and red blood cell distribution width (RDW) in the prognostic evaluation of colorectal cancer patients. 143 patients with colorectal cancer from January 2016 to January 2019 were selected by our hospital, and then, other 143 cases of physical examiners as normal groups were selecting to proceed colonoscopic biopsy to diagnose 106 cases of precancerous diseases related to colorectal cancer. Among them were the inflammatory bowel group (n = 56) and the colorectal polyp group (n = 50). Analysis of the survival impact factors of patients with carcinoma of the rectum, preoperative NLR, ROW, PLR, and prognostic relationship, and comparison of NLR, PLR, and RDW diagnostic rate and expression were performed. Tissue type, TNM stage, lymph node metastasis, NLR, RDW, and PLR had a predictive influence on patients with colorectal cancer (P0.05). There was no link between gender, age, aetiology, pathological type, and prognosis in patients with colorectal cancer (P > 0.05). Multiple variables in patients with colorectal cancer are affected by tissue categorization (poor differentiation), TNM stages (III, IV), lymph node metastases, NLR, ROW, and PLR (P0.05). When compared to solo NLR, Row, and PLR diagnostics, the combination diagnosis and malignancy rates were greater, and the differences were statistically significant (P0.05). Diagnostic sensitivity, specificity, and accuracy were greater when compared to single NLR, ROW, and PLR. When compared to the normal control group, NLR, ROW, and PLR have greater levels, and the differences are statistically significant (P0.05). The patient survival declines more slowly as PLR, NLR, and the severity of the condition rises. NLR, ROW, and PLR combined diagnosis has high accuracy in colorectal cancer diagnosis, and the prognosis of patients with NLR, ROW, and PLR levels has a tight association; so, clinically, the above signs should be identified, and the optimal treatment time is grasped. | Authentic |
Text : Altered expression of the p16 tumor suppressor is frequently found in prostate cancer, but its role for tumor development and patient prognosis is disputed. In order to clarify the prognostic role of p16 and to draw conclusions on interactions with key molecular features of prostate cancer, we studied p16 expression in a tissue microarray (TMA) with more than 12,400 prostate cancers and attached clinical, pathological, and molecular data such as ERG status and deletions of 3p13, 5q21, 6q15, and PTEN. p16 immunostaining was absent in non-neoplastic prostate cells but was found in 37 % of 9627 interpretable prostate cancers. Finding p16 expression in 58 % of ERG positive but in only 22 % of ERG negative cancers (p < 0.0001), highlights the known androgen-dependence of both genes. Significant associations between p16 upregulation and tumor phenotype or patient prognosis were strictly limited to the subset of ERG negative cancers. For example, p16 positivity increased from 15 % in Gleason ≤3 + 3 to 38 % in Gleason ≥4 + 4 cancers (p < 0.0001) and was associated with early PSA recurrence (p < 0.0001). p16 upregulation was strongly linked to deletions of PTEN (p < 0.0001), highlighting the interaction of both genes in growth control. In conclusion, p16 upregulation is a strong prognostic factor in ERG negative cancers. The strict limitation of its prognostic impact to a molecularly defined subgroup challenges the concept of molecular prognosis testing without considering molecular subtypes. | Authentic |
Text : Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and thromboxane A2. Platelet-colon cancer cell interactions potentiated the release of platelet-derived extracellular vesicles (EVs) rather than cancer cell-derived EVs. Our data show that single colon cancer cells were capable of recruiting and activating platelets and generating fibrin in plasma under shear flow. Finally, in a retrospective analysis of colon cancer patients, we found that the number of venous thromboembolism events was 4.5 times higher in colon cancer patients than in a control population. In conclusion, our data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients. Our work may provide rationale for targeting platelet-cancer cell interactions with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis, balancing safety with efficacy. | Authentic |
Text : This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).
This article has been retracted at the request of the Editor-in-Chief as panels from Figure 4A appear similar to each other.
Given the comments of Dr Elisabeth Bik regarding this article “This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article. | Authentic |
Text : The histone lysine methyltransferases contain a SET domain, which catalyzes the addition of methyl groups to specific lysine residues. The MLL family of genes encodes histone-modifying enzymes with histone 3-lysine 4 methyltransferase activity that can regulate gene transcription. The MLL family exists in multi-protein complexes and has been implicated in a variety of processes including normal development and cell growth. Although some of the MLL family members have already been described to be involved in cancer, a clear relationship of these genes with breast cancer is not determined to date. In the present study, we used quantitative PCR to investigate the expression profile of all five MLL genes [MLL (ALL-1), MLL2, MLL3, MLL4 and MLL5] in 7 breast cancer cell lines, 8 breast tumors and adjacent non-tumor tissues and in 12 normal tissues. We observed a diminished expression of all five genes in the breast cancer cell lines when compared to normal breast tissue. We found a significantly decreased expression of MLL2 in the tumor samples compared to the non-tumor controls. In tumor samples, MLL5 also showed a clear suppression tendency. Among the normal tissues analyzed, all genes showed a markedly higher expression in skeletal muscle and brain. Although further studies are required to determine the exact role of these methyltransferases in cancer development, our results indicate that the suppression of MLL genes, especially MLL2 and 5, take part in modulating breast carcinogenesis. Our assessment of the MLL family gene expression patterns in a diverse set of breast cancer cell lines and in a multitude of tissue types and breast tumors should lead to increasingly detailed information on the involvement of these genes in cancer progression. | Authentic |
Text : Gastric cancer (GC) is among the most aggressive types of cancer and is the second leading cause of cancer-associated mortality worldwide. The specific role of deregulated expression/activity of histone methyltransferases (HMTs) in GC is poorly understood. The present study aimed to explore the possible oncogenic role of euchromatic histone lysine methyltransferase 1 (EHMT1) in gastric carcinogenesis. It was identified that EHMT1 was highly expressed in GC tissues compared with that in adjacent non-tumor tissues, and that EHMT1 expression levels were significantly associated with tumor stage and lymph node metastasis. Through knockdown of EHMT1 in the BGC-803 cell line, EHMT1 was demonstrated to promote a malignant phenotype, and to increase the wound healing, migration and invasion abilities of GC cells. Corresponding to these in vitro results, knockdown of EHMT1 also inhibited the peritoneal metastasis of GC cells in vivo. Furthermore, EHMT1 also regulated the expression of the epithelial-mesenchymal transition marker E-cadherin in vitro and in vivo. These results indicate that EHMT1 is upregulated in GC and serves an oncogenic role in GC development by regulating E-cadherin expression. | Counterfeit |
Text : Osteosarcoma (OS) is a malignant tumor characterized by the direct production of bone or osteoid tissues by proliferating tumor cells. Suppressor of variegation 3-9 homolog 2 (SUV39H2) is implicated in the occurrence of OS. Therefore, we designed this study to investigate effects of SUV39H2 in OS meditated by the lysine specific demethylase-1/E-cadherin (LSD1/CDH1) axis. Clinical OS tissues and paracancerous tissues were collected for analysis of SUV39H2, LSD1 and CDH1 expression, and Kaplan-Meier survival analysis was applied to test the relationship between SUV39H2 expression and overall survival. Loss- and gain-of-function assays were conducted to determine the roles of SUV39H2, LSD1 and CDH1 in OS epithelial mesenchymal transition (EMT) and migration in OS cells, with quantitation of relevant proteins by immunofluorescence. We confirmed the effects of modulating the SUV39H2/CDH1 axis in a mouse OS tumor model. SUV39H2 and LSD1 were highly expressed, while CDH1 was downregulated in OS tissues and cells. SUV39H2 expression correlated inversely with overall survival of patients with OS. SUV39H2 positively regulated LSD1 expression, while LSD1 negatively regulated CDH1 expression. SUV39H2 or LSD1 overexpression, or CDH1 silencing promoted migration and EMT, as indicated by reduced E-cadherin and dramatically upregulated Vimentin and N-cadherin of OS cells. SUV39H2 expedited the progression of OS, which was reversed by CDH1 repression in the setting of OS in vitro and in vivo. Collectively, our results demonstrate highly expressed SUV39H2 in OS elevates the expression of LSD1 to downregulate CDH1 expression, thereby aggravating OS, providing a potential therapeutic target for treatment of OS. | Counterfeit |
Text : Hepatocellular carcinoma (HCC) is one of the leading cancers in the world in incidence and mortality. Current pharmacotherapy of HCC is limited in the number and efficacy of anticancer agents. Metabolic reprogramming is a prominent feature of many cancers and has rekindled interest in targeting metabolic proteins for cancer therapy. Glycogen is a storage form of glucose, and the levels of glycogen have been found to correlate with biological processes in reprogrammed cancer cells. However, the contribution of glycogen metabolism to carcinogenesis, cancer cell growth, metastasis, and chemoresistance is poorly understood. Thus, we studied the processes involved in the inhibition of glycogen metabolism in HCC cells. Pharmacological inhibition of glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen catabolism, by CP-91149 led to a decrease in HCC cell viability. GP inhibition induced cancer cell death through the intrinsic apoptotic pathway. Mitochondrial dysfunction and autophagic adaptations accompanied this apoptosis process whereas endoplasmic reticulum stress, necrosis, and necroptosis were not major components of the cell death. In addition, GP inhibition potentiated the effects of multikinase inhibitors sorafenib and regorafenib, which are key drugs in advanced-stage HCC therapy. Our study provides mechanistic insights into cell death by perturbation of glycogen metabolism and identifies GP inhibition as a potential HCC pharmacotherapy target. | Authentic |
Text : Ovarian cancer (OC) is a lethal gynecologic tumor, which brings its mortality to the head. CXCL12 and its receptor chemokine receptor 4 ( CXCR4) have been found to be highly expressed in OC and contribute to the disease progression by affecting tumor cell proliferation and invasion. Here, in this study, we aim to explore whether the blockade of CXCL12-CXCR4 axis with AMD3100 (a selective CXCR4 antagonist) has effects on the progression of OC. On the basis of the gene expression omnibus database of OC gene expression chips, the OC differentially expressed genes were screened by microarray analysis. OC (nonmetastatic and metastatic) and normal ovarian tissues were collected to determine the expressions of CXCL12 and CXCR4. A series of AMD3100, shRNA against CXCR4, and pCNS-CXCR4 were introduced to treat CAOV3 cells with the highest CXCR4 was assessed. Cell viability, apoptosis, migration, and invasion were all evaluated. The microarray analysis screened out the differential expression of CXCL12-CXCR4 in OC. CXCL12 and CXCR4 expressions were increased in OC tissues, particularly in the metastatic OC tissues. Downregulation of CXCR4 by AMD3100 or shRNA was observed to have a critical role in inhibiting cell proliferation, migration, and invasion of the CAOV3 OC cell line while promoting cell apoptosis. Overexpressed CXCR4 brought significantly promoting effects on the proliferation and invasiveness of OC cells. These results reinforce that the blockade of CXCL12-CXCR4 axis with AMD3100 inhibits the growth of OC cells. The antitumor role of the inhibition of CXCL12-CXCR4 axis offers a preclinical validation of CXCL12-CXCR4 axis as a therapeutic target in OC. | Counterfeit |
Text : The etiology of pancreatic cancer (PC) remains poorly understood. High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. The aim of this study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for PC. A case-control study was conducted to examine plasma ferritin levels (n = 1,000 cases; 1,004 controls), two hemochromatosis gene (HFE) SNPs (n = 1,386 cases; 1,386 controls), and PC risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by unconditional logistic regression. We did not observe a significant association between plasma ferritin and PC risk. However, HFE rs1799945 was significantly associated with PC risk, with each additional copy of minor allele T being associated with a 1.21-fold increased risk of PC (OR = 1.21, 95 % CI 1.05-1.39, P = 7.72 × 10(-3)). Overall, high iron levels do not increase the risk of PC. Our observation that HFE rs1799945 increased PC risk warrants replication in additional study populations. | Authentic |
Text : Programmed death ligand 1 (PD-L1) is overexpressed in some metastatic breast cancer subtypes, specifically triple-negative breast cancer (TNBC). This feature can assist in the eradication of anti-tumor immunity, thereby enhancing the survival of the tumor. This study aims to explore how sesamin affects PD-L1 expression in breast cancer cells and its related molecular mechanisms. We found high levels of expression of PD-L1 in both mRNA and protein levels in the TNBC cell line, MDA-MB231, but not in the luminal type-breast cancer cell line, MCF-7. We then demonstrated the tumor suppressive effect of sesamin, which induced the inhibition of cell proliferation in MDA-MB231 cells. Additionally, sesamin triggered PD-L1 downregulation (both mRNA and protein) through the inhibition of AKT, NF-κB and JAK/Stat signaling in MDA-MB231 cells. Moreover, the migration ability of MDA-MB231 cells was effectively diminished by sesamin via inhibition of the activation of MMP-9 and MMP-2. In summary, this study demonstrated that sesamin suppresses MDA-MB231 breast cancer cells' proliferation and migration; and decreases the expression of PD-L1 via the downregulation of AKT, NF-κB, and JAK/Stat signaling. Therefore, sesamin may be an effective alternative and novel therapeutic option for immunotherapy in breast cancer cells with high PD-L1 expression. | Authentic |
Text : To investigate the expression of human myozenin 2 (MYOZ2) in cancer tissues and its effect on the prognosis of patients with gastric cancer. Gastric cancer tissue and adjacent normal tissue specimens were obtained from a total of 258 patients together with complete clinicopathological data. Those patients were treated in Harbin Medical University Cancer Hospital from March 2007 to March 2012. Quantitative Real Time-Polymerase Chain Reaction (RT-PCR) was used to detect the expression of MYOZ2 messenger RNA (mRNA) in gastric cancer tissues and normal gastric tissues, and correlations between the expression level of MYOZ2 in gastric cancer tissues and the clinicopathological parameters of patients were analyzed. MYOZ2 protein expression levels in different gastric cancer cells were detected by Western blotting; transwell chamber assay was used to detect the effect of MYOZ2 expression on the in-vitro migration and invasion abilities of gastric cancer cells; 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to examine the in-vitro proliferation and growth abilities of gastric cancer cells. The expression level of MYOZ2 mRNA in gastric cancer tissues was significantly higher than that in cancer-adjacent tissues in 258 cases (p<0.05). Western blotting results showed that the expression level of MYOZ2 protein in gastric cancer tissues was significantly increased compared with that in the corresponding adjacent healthy tissues (p<0.05). In-vitro growth, migration and invasion abilities of MYOZ2 positive gastric cancer cells were significantly higher than those of normal tissue cells. Univariate analysis showed that the high expression level of MYOZ2 in gastric cancer tissues was closely related to tumor size, lymph node metastasis, and pathological tumor-node-metastasis (pTNM) staging (p<0.05), but not associated with gender, age, differentiation degree, and tumor location (p>0.05). The 1-, 3- and 5-year survival rates of patients with low expression level of MYOZ2 (n=130) were higher than those of patients with high expression level of MYOZ2 (n=128). Multivariate analysis revealed that the expression level of MYOZ2 (p=0.000), lymph node metastasis (p=0.002), and pTNM staging (p=0.015) were independent risk factors influencing the prognosis of gastric cancer. Our results showed that the expression level of MYOZ2 may play an important role in the occurrence and development of gastric cancer, and can also provide references for the clinical diagnosis and treatment of gastric cancer. | Authentic |
Text : Mortality-to-incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. Ether-à-go-go-1 (Eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, identifying potent and specific Eag1 channel inhibitors is crucial. In this study, we identified the first natural inhibitor of Eag1, the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine directly interacted with Eag1 and inhibited the currents in a concentration-dependent manner (IC50 of 69.97 ± 5.2 μM), and the amino acids Ile 550 , Thr 552 , and Gln 557 in the Eag1 C-linker domain were critical for tetrandrine's inhibitory effect. Moreover, tetrandrine reduced the proliferation of HeLa cells and Chinese hamster ovary (CHO) cells stably expressing Eag1 in a concentration-dependent manner. Finally, tetrandrine (30 mg/kg/day) inhibited tumor growth in mice, demonstrating a 64.21% inhibitory rate of HeLa cell-transplanted tumors. These results suggest that tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction-induced diseases. | Authentic |
Text : We performed a meta-analysis to evaluate the value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) for the detection of second primary cancers in cancer patients. This present study analyzed a total of 6 selected studies (1374 patients). The sensitivity and specificity of PET-CT were 0.84 (95% confidence interval [CI] = 0.66 to 0.93), and 0.98 (95% CI = 0.97 to 0.98). Area under the curve was 0.98 (95% CI = 0.96 to 0.99). Studies were systematically searched for relevant PET-CT original articles in the MEDLINE and EMBASE databases. We calculated the pooled sensitivity, specificity, and likelihood ratios for 18FDG PET-CT. We also constructed the summary receiver-operating characteristic curve for 18FDG PET-CT. 18FDG PET-CT has high sensitivity and specificity for the detection of second primary cancers in cancer patients. | Authentic |
Text : Esophageal squamous cell carcinoma (ESCC) is the most malignant type of esophageal cancer. Although significant advances have been made in ESCC diagnosis and therapy, its poor pathogenesis and prognosis remain a life-threatening problem. Meanwhile, long noncoding RNAs (lncRNAs) exert a pivotal function in tumorigenesis. In this research, we aimed to explore the association between the aberrant expression of lncRNA DLX6-AS1 and the development and metastasis of ESCC. DLX6-AS1 expression was monitored by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in ESCC specimens. Moreover, experiments were conducted to detect the effect of DLX6-AS1 on the cell proliferation and metastasis of ESCC. In addition, the underlying mechanism was further explored through luciferase assays and RNA immunoprecipitation assay (RIP). DLX6-AS1 expression level was significantly higher in ESCC specimens. Moreover, cell proliferation and metastasis of ESCC cells could be inhibited via reducing DLX6-AS1 expression. Besides, DLX6-AS1 was regarded as an oncogene in ESCC. Furthermore, DLX6-AS1 acted as a competing endogenous RNA via sponging miR-577 in ESCC. In summary, DLX6-AS1 promotes development and metastasis of ESCC by sponging miR-577 and could be a potential therapeutic target. | Counterfeit |
Text : Cellular microbiology, which is the interaction between harmful microbes and infected cells, is important in the determination of the bacterial infection processes and in the progression of data of different cellular mechanisms. The therapeutic role of bacteria has gained attention since the known methods such as radiation, chemotherapy, and immunotherapy have got drawbacks. Bacteria have demonstrated a favorable impact in treating cancer through eradication of tumors. Bacteria, in cancer treatment, have proven to be promising and have been shown in some of the previous work that it can successfully suppress the growth of tumors. In this paper, we analyzed the difficulties and settlement for using bacteria in cancer therapy as well the mechanisms in which bacteria works in order to achieve tumor eradication. Future works may focus on the use of bacteria along with other treatments in order to achieve effective tumor therapy. | Authentic |
Text : Pancreatic cancer (PC) stands out as one of the most lethal cancers. Due to late diagnosis, only a fraction of patients can be resected. Although it still has significant adverse effects and poor results, the treatment is connected with better overall survival than the prior treatment. Thus, new alternative therapy for advanced PC is needed. Materials/Methods. The impact of 10058-F4 and curcumin combination therapy on apoptosis and cell growth in SW1990 pancreatic cancer cells were determined in vitro using the CCK-8 assay and flow cytometry of Annexin V-FITC/PI, and the in vivo antitumor effect was determined utilizing SW1990-bearing pancreatic tumor mouse models induced by subcutaneous implantation. At concentrations of (10 mol/L+2 mol/L), 10058-F4+curcumin obtained the highest rate of SW1990 cell death, and they had a beneficial effect on SW1990 pancreatic tumor-bearing animals. Furthermore, c-Myc, Akt phosphorylation, and the expression of apoptosis-related molecular were reduced, and the combination therapy modified the expression of apoptosis-related molecular. In vitro and in vivo, the combination of 10058-F4 plus curcumin has antipancreatic cancer actions that are substantially effective. | Counterfeit |
Text : Our research was aimed at investigating the biological character of human leukocyte antigen complex group 18 (HCG18) on gastric cancer (GC) progression and its potential mechanisms. The expression characteristics and prognostic values of HCG18 in GC were evaluated through the GEPIA database and Kaplan-Meier plotter database. Quantitative real-time PCR and Western blot were used for quantification of messenger RNA expression, microRNA (miRNA) expression and protein expression. Cell proliferation, migration and invasion were detected by cell counting kit-8 assay, 5'-bromo-2'-deoxyuridine assay and Transwell assay, respectively. Dual-luciferase reporter gene assay and RNA immunoprecipitation assay were used for examination of the interactions among HCG18, miR-370-3p and epidermal growth factor receptor (EGFR) 3'UTR. HCG18 expression was up-regulated in GC tissues, and its high expression was closely associated with increased tumour size, advanced TNM stage, poor differentiation of tumour tissues and unfavourable prognosis of patients with GC. Additionally, HCG18 overexpression promoted the proliferation, migration and invasion of GC cells, and its knockdown suppressed the malignant phenotypes of GC cells. Furthermore, HCG18 served as a miRNA sponge to repress miR-370-3p and indirectly up-regulated EGFR expression in GC cells. HCG18 served as a tumour-promoting factor in GC progression by modulating the miR-370-3p/EGFR axis. | Counterfeit |
Text : TP53 plays critical roles in sensitivity to chemotherapy, and aging. Collagen is very important in aging. The molecular structure and biochemical properties of collagen changes during aging. The discoidin domain receptor (DDR1) is regulated in part by collagen. Elucidating the links between TP53 and DDR1 in chemosensitivity and aging could improve therapies against cancer and aging. Restoration of WT-TP53 activity resulted in increased sensitivity to chemotherapeutic drugs and elevated expression of key components of the Raf/MEK/ERK, PI3K/Akt and DDR1 pathways. DDR1 could modulate the levels of Raf/MEK/ERK and PI3K/Akt pathways as well as sensitize the cells to chemotherapeutic drugs. In contrast, suppression of WT TP53 with a dominant negative (DN) TP53 gene, suppressed DDR1 protein levels and increased their chemoresistance. Restoration of WT TP53 activity or increased expression of the anti-aging DDR1 collagen receptor can result in enhanced sensitivity to chemotherapeutic drugs. Our innovative studies indicate the important links between WT TP53 and DDR1 which can modulate Raf/MEK/ERK and PI3K/Akt signaling as well as chemosensitivity and aging. We investigated the roles of wild type (WT) and mutant TP53 on drug sensitivity of prostate cancer cells and the induction of Raf/MEK/ERK, PI3K/Akt and DDR1 expression and chemosensitivity. | Authentic |
Text : Expression of the retinoic acid-induced protein 3 (RAI3) has been suggested to predict clinical outcome in a variety of malignancies. However, its role in esophageal cancers remains unclear. Immunohistochemical RAI3 staining was analyzed on tissue microarrays containing 359 esophageal adenocarcinomas (EAC) and 254 esophageal squamous cell carcinomas (ESCC). RAI3 immunostaining was typically absent or weakly detectable in the membranes in benign esophageal tissues. RAI3 staining was higher in malignant than in benign esophagus epithelium. High-levels of RAI3 staining were found in 79.2% of interpretable EACs and 55.9% of ESCCs. In EACs, strong RAI3 staining was associated with advanced pathological tumor stage (p < .0001), high UICC stage (p < .0001), high tumor grade (p = .0133), and positive lymph nodal status (p = .0002). Additionally, high RAI3 staining predicted shortened overall survival of EAC and ESCC patients (p = .0298 and p = .0227). RAI3 overexpression is associated with poor prognosis in esophageal cancers. We propose that RAI3 overexpression might play a biologically relevant role of RAI3 in esophageal cancers. | Authentic |
Text : Chemotherapy drug-induced nephrotoxicity limits clinical applications for treating cancers. Pyroptosis, a newly discovered programmed cell death, was recently reported to be associated with kidney diseases. However, the role of pyroptosis in chemotherapeutic drug-induced nephrotoxicity has not been fully clarified. Herein, we demonstrate that the chemotherapeutic drug cisplatin or doxorubicin, induces the cleavage of gasdermin E (GSDME) in cultured human renal tubular epithelial cells, in a time- and concentration-dependent manner. Morphologically, cisplatin- or doxorubicin-treated renal tubular epithelial cells exhibit large bubbles emerging from the cell membrane. Furthermore, activation of caspase 3, not caspase 9, is associated with GSDME cleavage in cisplatin- or doxorubicin-treated renal tubular epithelial cells. Meanwhile, silencing GSDME alleviates cisplatin- or doxorubicin-induced HK-2 cell pyroptosis by increasing cell viability and decreasing LDH release. In addition, treatment with Ac-DMLD-CMK, a polypeptide targeting mouse caspase 3-Gsdme signaling, inhibits caspase 3 and Gsdme activation, alleviates the deterioration of kidney function, attenuates renal tubular epithelial cell injury, and reduces inflammatory cytokine secretion in vivo. Specifically, GSDME cleavage depends on ERK and JNK signaling. NAC, a reactive oxygen species (ROS) inhibitor, reduces GSDME cleavage through JNK signaling in human renal tubular epithelial cells. Thus, we speculate that renal tubular epithelial cell pyroptosis induced by chemotherapy drugs is mediated by ROS-JNK-caspase 3-GSDME signaling, implying that therapies targeting GSDME may prove efficacious in overcoming chemotherapeutic drug-induced nephrotoxicity. | Authentic |
Text : Natural killer cells are an important part of the innate immune system mediating robust responses to virus-infected and malignant cells without needing prior antigen priming. NK cells have always been thought to be short-lived and with no antigen specificity; however, recent data support the presence of NK cell memory including in the hapten-specific contact hypersensitivity model and in certain viral infections. The memory-like features can also be generated by short-term activation of both murine and human NK cells with cytokine combination of IL-12, IL-15 and IL-18, imparting increased longevity and enhanced anticancer functionality. Preclinical studies and very early clinical trials demonstrate safety and very promising clinical activity of these cytokine-induced memory-like (CIML) NK cells, making them an attractive cell type for developing novel adoptive cellular immunotherapy strategies. Furthermore, efforts are on to arm them with novel gene constructs for enhanced tumor targeting and function. | Authentic |
Text : Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono- and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation. | Authentic |
Text : Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. MicroRNA (miRNA), a class of noncoding single-stranded RNA molecules, is involved in regulating cancer cell proliferation, metastasis, migration, invasion, and apoptosis. We showed that the expression of miR-346 was significantly increased in HCC tissues and cell lines, compared with noncancerous controls, and was associated with poor prognosis. Overexpression of miR-346 promoted proliferation and inhibited apoptosis of SMMC-7721 cells, while knockdown of miR-346 significantly suppressed proliferation and induced apoptosis of HepG2 cells. Then we identified breast cancer metastasis suppressor 1 (BRMS1) as a direct target of miR-346 based on luciferase reporter assays. There was a negative correlation between miR-346 and BRMS1 expression at both the protein and mRNA levels. Furthermore, inhibition of BRMS1 expression reversed the tumor-suppression effects of miR-346 downregulation in HepG2 cells. These results indicate that miR-346 promotes HCC progression by regulating BRMS1 expression. | Authentic |
Text : Here we explored the antitumor-activity of novel-formulated-form of curcumin (phytosomal-encapsulated-curcumin) or in combination with 5-FU in breast cancer. The antiproliferative activity was assessed in 2D and 3-dimensional cell-culture-model. The migratory-behaviors of the cells were determined by migration assay. The expression levels of CyclinD1,GSK3a/b, P-AMPK, MMP9, and E-cadherin were studied by qRT-PCR and/or Western blotting. The anti-inflammatory of nano-curcumin was assessed, while antioxidant activity was evaluated by malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total thiols (T-SH). To understand dynamic behavior of genes, we reconstructed a Boolean network, while the robustness of this model was evaluated by Hamming distance. phytosomal-curcumin suppressed cell-growth followed by tumor-shrinkage in 3D model through perturbation of AMP-activated protein kinase. Curcumin reduced the invasiveness of MCF-7 through perturbation of E-cadherin. Moreover, phytosomal-curcumin inhibited the tumor growth in xerograph model. Histological staining of tumor tissues revealed vascular disruption and RBC extravasation, necrosis, tumor stroma, and inflammation. Co-treatment of curcumin and 5-FU reduced the lipid-peroxidation and increased MDA/SOD level. Of note, curcumin reduced cyclinD-expression in breast cancer cell treated with thrombin, and activates AMPK in a time-dependent manner. Also suppression of AMPK abrogated inhibitory effect of phytosomal-curcumin on thrombin-induced cyclin D1 over-expression, suggesting that AMPK is essential for anti-proliferative effect of this agent in breast cancer. Our finding demonstrated that phytosomal-curcumin antagonizes cell growth and migration, induced by thrombin through AMP-Kinase in breast cancer, supporting further-investigations on the therapeutic potential of this novel anticancer agent in treatment of breast cancer. | Authentic |
Text : miR-1284 has been reported to inhibit tumor growth in some human cancers, including lung cancer, ovarian cancer, and gastric cancer. Whether it regulates breast cancer progression remains elusive. In this study, we found that miR-1284 was downregulated in breast cancer tissues and cell lines compared to normal control cells. Moreover, we showed that overexpression of miR-1284 significantly inhibited the proliferation, migration, and invasion of breast cancer cells while promoting apoptosis. In terms of mechanism, we found that transcription factor ZIC2 was a target of miR-1284 in breast cancer cells. Through the luciferase reporter assay, we demonstrated their direct interaction. RT-qPCR and Western blot also indicated that miR-1284 overexpression inhibited the protein levels of ZIC2 in breast cancer cells. Moreover, we found that ZIC2 knockdown inhibited the proliferation, migration, and invasion of breast cancer cells, whereas restoration of ZIC2 reversed the effects of miR-1284 on breast cancer cells. Taken together, our findings demonstrated that miR-1284 suppressed the proliferation, migration, and invasion of breast cancer cells via targeting ZIC2, which provided a new insight on the development of therapeutic targets for breast cancer treatment. | Authentic |
Text : The cancer stem cell theory states that a subset of tumor cells, termed cancer stem cells (CSCs), has the ability to self-renew and differentiate within the tumors. According to this theory, CSCs would be mainly responsible for tumor initiation, progression, resistance to therapy, recurrence, and metastasis. In this study, a culture system was setup to enrich CSCs from bladder cancer (T24), lung cancer (A549), colorectal cancer (CaCo-2), and osteosarcoma (MG63) cell lines, through sphere formation. Magnetic-activated cell sorting was also used to further increase CSC enrichment. Subsequently, molecular characterization of CSC-enriched cell populations and parental cells was carried out, by exploring the expression levels of stem markers and the enzyme nicotinamide N-methyltransferase (NNMT). Results obtained showed a significant upregulation of stem cell markers in CSC-enriched populations, obtained upon sphere formation, compared with parental counterparts. Moreover, NNMT expression levels were markedly increased in samples enriched with CSCs with respect to control cells. Considering the fundamental role played by CSCs in carcinogenesis, reported data strengthen the hypothesis that sustains a pivotal role of NNMT in cancer growth and metastasis. In addition, these findings could represent an important achievement for the development of new and effective anticancer therapies, based on CSC-associated targets. | Authentic |
Text : Cancer neurobiology is an emerging discipline that inevitably unfurls new perspectives in oncology. The role that nerves play in cancer progression resonates with the long-reported dependency of tumors on neuro-molecular mechanisms that remain insufficiently elucidated. Whereas interactions between neurotrophic growth factors and receptors have been heavily studied in the nervous system, their expression in cancers and their impact on tumor cell growth and metastasis through their corresponding signaling pathways has been undervalued. Accumulating evidence suggests that trophic factors released by nerves strongly influence tumor development and that this neural contribution appears to not only play a stimulatory role but also function as an essential part of the tumor's microenvironment. This bidirectional communication between proliferating cells and tumor-infiltrating nerves drives axonogenesis and tumor growth and migration. Acquiring a better understanding of the trophic interactions between primary afferent neurons and invading tumors will guide clinically actionable strategies to prevent tumor-associated axonogenesis, disrupting the chemical crosstalk between neurons and tumors and ultimately decreasing tumor growth and spread. | Authentic |
Text : Toxin-antitoxin (TA) systems are two-component genetic modules widespread in bacterial and archaeal genomes, in which the toxin module is rendered inactive under resting conditions by its antitoxin counterpart. Under stress conditions, however, the antitoxin is degraded, freeing the toxin to exert its lethal effects. Although not evolved to function in eukaryotes, some studies have established the lethal activity of these bacterial toxins by inducing apoptosis in mammalian cells, an effect that can be neutralized by its cognate antitoxin. Inspired by the way the toxin can become active in eukaryotes cells, we produced an engrained yoeB-yefM TA system to selectively kill human breast cancer cells expressing a high level of miR-21. Accordingly, we generated an engineered yefM antitoxin gene with eight miR-21 target sites placed in its 3'untranslated region. The resulting TA system acts autonomously in human cells, distinguishing those that overexpress miR-21, killed by YoeB, from those that do not, remaining protected by YefM. Thus, we indicated that microRNA-control of the antitoxin protein of bacterial TA systems constitutes a novel strategy to enhance the selective killing of human cancer cells by the toxin module. The present study provides significant insights for developing novel anticancer strategies avoiding off-target effects, a challenge that has been pursued by many investigators over the years. | Authentic |
Text : We aimed to investigate the bio-functions of METTL3 in promoting breast cancer (BCa) progression via regulating N6-methyladenosine (m6A) modification of EZH2 mRNA. METTL3 levels in 48 cases of BCa and matched paracancerous tissues were detected. In the meantime, METTL3 in BCa patients with different staging or lymphatic metastasis states were examined. Prognosis of the BCa patients was analyzed using Kaplan-Meier estimator. Protein levels of EMT-associated genes and invasive and migratory abilities were evaluated. The binding relationship between EZH2 and METTL3 was analyzed via RIP. Besides, m6A modification of EZH2 mRNA was explored. E-Cadherin level in MCF-7 cells with EZH2 knockdown was tested. Subsequently, ChIP was done to verify the interaction between E-cadherin and EZH2. Regulatory effects of METTL3/E-cadherin axis on EMT and metastasis of BCa were finally determined. METTL3 was upregulated in BCa tissues compared to paracancerous ones. METTL3 was especially higher in T3-T4 BCa or those with lymphatic metastasis. BCa patients expressing high level of METTL3 experienced worse survival. METTL3 was identically upregulated in BCa cell lines. Knockdown of METTL3 in MCF-7 cells attenuated EMT and metastatic abilities. Protein level of EZH2 was downregulated after knockdown of METTL3 in MCF-7 cells, while its mRNA level was not influenced by METTL3. Furthermore, METTL3 was confirmed to interact with EZH2, and m6A modification existed in EZH2 mRNA. Knockdown of EZH2 greatly upregulated mRNA level of E-cadherin, and later, ChIP assay confirmed the interaction between EZH2 and E-cadherin. E-Cadherin could abolish the effects of METTL3 on BCa metastasis and epithelial-mesenchymal transition. METTL3 is upregulated in BCa. It could regulate the protein level of EZH2 through m6A modification to promote EMT and metastasis in BCa cells, thereafter aggravating the progression of BCa. | Authentic |
Text : The blood-tumor barrier (BTB) limits the transport of chemotherapeutic drugs to brain tumor tissues and impacts the treatment of glioma. Long non-coding RNAs play critical roles in various biological processes of tumors; however, the function of these in BTB permeability is still unclear. In this study, we have identified that long intergenic non-protein coding RNA 174 (linc00174) was upregulated in glioma endothelial cells (GECs) from glioma tissues. Additionally, linc00174 was also upregulated in GECs from the BTB model in vitro. Knock down of linc00174 increased BTB permeability and reduced the expression of the tight junction-related proteins ZO-1, occludin, and claudin-5. Both bioinformatics data and results of luciferase reporter assays demonstrated that linc00174 regulated BTB permeability by binding to miR-138-5p and miR-150-5p. Furthermore, knock down of linc00174 inhibited FOSL2 expression via upregulating miR-138-5p and miR-150-5p. FOSL2 interacted with the promoter regions and upregulated the promoter activity of ZO-1, occludin, claudin-5, and linc00174 in GECs. In conclusion, the present study demonstrated that the linc00174/miR-138-5p (miR-150-5p)/FOSL2 feedback loop played an essential role in regulating BTB permeability. | Authentic |
Text : Cervical cancer is the fourth most common malignancy in women. The aim of this study was to investigate the functions of Ezrin in cervical cancer cells. Two cervical cancer cell lines, SiHa and CaSki, were cultured in vitro. Following the knockdown of Ezrin using siRNA, real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were applied to analyze Ezrin expression at the messenger RNA (mRNA) and protein levels. Subsequently, wound healing assay, transwell assay, and sulforhodamine B (SRB) assay were used to detect the migration, invasion, and viability of cervical cancer cells, respectively. Results revealed that Ezrin siRNA can notably inhibit the migration and invasion of SiHa and CaSki cells (P < 0.05). However, knockdown of Ezrin shows no effects on the viability of SiHa and CaSki cells (P < 0.05). It is indicated that Ezrin plays a possible role in promoting the migration and invasion of cervical cancer cells and may be a therapeutic target to prevent metastasis of cervical cancer. | Authentic |
Text : Breast cancer is the leading cancer in women, which accounts for millions of deaths worldwide. Early and accurate detection, prognosis, cure, and prevention of breast cancer is a major challenge to society. Hence, a precise and reliable system is vital for the classification of cancerous sequences. Machine learning classifiers contribute much to the process of early prediction and diagnosis of cancer. In this paper, a comparative study of four machine learning classifiers such as random forest, decision tree, AdaBoost, and gradient boosting is implemented for the classification of a benign and malignant tumor. To derive the most efficient machine learning model, NCBI datasets are utilized. Performance evaluation is conducted, and all four classifiers are compared based on the results. The aim of the work is to derive the most efficient machine-learning model for the diagnosis of breast cancer. It was observed that gradient boosting outperformed all other models and achieved a classification accuracy of 95.82%. | Authentic |
Text : Skin cutaneous melanoma (SKCM) is one of the most destructive skin malignancies and has attracted worldwide attention. However, there is a lack of prognostic biomarkers, especially tumour microenvironment (TME)-based prognostic biomarkers. Therefore, there is an urgent need to investigate the TME in SKCM, as well as to identify efficient biomarkers for the diagnosis and treatment of SKCM patients. A comprehensive analysis was performed using SKCM samples from The Cancer Genome Atlas and normal samples from Genotype-Tissue Expression. TME scores were calculated using the ESTIMATE algorithm, and differential TME scores and differentially expressed prognostic genes were successively identified. We further identified more reliable prognostic genes via least absolute shrinkage and selection operator regression analysis and constructed a prognostic prediction model to predict overall survival. Receiver operating characteristic analysis was used to evaluate the diagnostic efficacy, and Cox regression analysis was applied to explore the relationship with clinicopathological characteristics. Finally, we identified a novel prognostic biomarker and conducted a functional enrichment analysis. After considering ESTIMATEScore and tumour purity as differential TME scores, we identified 34 differentially expressed prognostic genes. Using least absolute shrinkage and selection operator regression, we identified seven potential prognostic biomarkers (SLC13A5, RBM24, IGHV3OR16-15, PRSS35, SLC7A10, IGHV1-69D and IGHV2-26). Combined with receiver operating characteristic and regression analyses, we determined PRSS35 as a novel TME-based prognostic biomarker in SKCM, and functional analysis enriched immune-related cells, functions and signalling pathways. Our study indicated that PRSS35 could act as a potential prognostic biomarker in SKCM by investigating the TME, so as to provide new ideas and insights for the clinical diagnosis and treatment of SKCM. | Authentic |
Text : As a common subtype of malignant gliomas, glioblastoma multiforme (GBM) is associated with poor prognosis. This study is aimed to examine the anticancer activities of alpinumisoflavone (AIF) and its underlying mechanisms. Our results demonstrated that AIF inhibited the proliferation of GBM cells (U373 and T98G) in a time and dose-dependent manner. In addition, flow cytometry analysis not only confirmed AIF arrested cell cycle at the G0/G1 phase but also the induced apoptosis of U373 and T98G cells. Western blotting also confirmed that AIF altered the expression levels of cell cycle-related proteins. Further mechanism studies revealed that AIF inhibited cell proliferation, induced G0/G1 phase arrest and induced apoptosis of U373 and T98G cells through activating PPARγ, as evidenced by the fact that GW9662 (PPARγ inhibitor) could effectively reverse the effects of AIF on U373 and T98G cells. Furthermore, the in vivo study also revealed that AIF suppressed tumor growth and caused cell cycle arrest. Collectively, these results highlighted the potential use of AIF in the treatment of GBM. | Counterfeit |
Text : In previous years, progranulin (PGRN) has attracted increasing attention due to its oncogenic roles in several types of tumor. However, the clinical relevance of PGRN in gastric cancer remains to be elucidated. In the present study, 120 retrospective tissue samples were obtained from patients with primary gastric cancer, and the expression of PGRN was detected using immunohistochemistry. The results showed that 71 cases exhibited a high expression of PGRN, which was markedly higher than the 49 cases with a low expression of PGRN. Subsequent χ2 analysis confirmed for the first time, to the best of our knowledge, that a high level of PGRN was positively correlated with lymph node metastasis (P=0.048), lymphatic invasion (P=0.018) and advanced clinical stage (P=0.027). Survival analysis showed that PGRN was positively correlated with poorer overall survival (OS; P=0.0043) and progression‑free survival (PFS; P=0.0022). Univariate and multivariate Cox regression analysis showed that PGRN and clinical stage had a significant effect on the OS and PFS of the patients with gastric cancer. In addition, cell experiments confirmed that extracellular PGRN promoted the intracellular expression of PGRN in a concentration‑dependent manner in gastric cancer cells. The AKT and extracellular signal‑regulated kinase signaling pathways were involved in the upregulation of intracellular PGRN induced by extracellular PGRN in MKN‑45 and MGC‑803 gastric cancer cells. Taken together, the results of the present study suggested that PGRN may be important in the progression and prognosis of gastric cancer, and that the expression of PGRN was regulated in a positive feedback loop. These findings enhance current knowledge regarding PGRN in tumors. | Authentic |
Text : NEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown. We detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR. We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression. Our results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer. | Authentic |
Text : Unusually high aneuploidy is a hallmark of epithelial serous ovarian cancer (SOC). Previous analyses have focused on aneuploidy on average across all tumor cells. With the expansion of single-cell sequencing technologies, however, an analysis of copy number heterogeneity cell-to-cell is now technically feasible. Here, we describe an analysis of single-cell RNA sequencing (scRNA-seq) data to infer arm-level aneuploidy in individual serous ovarian cancer cells. By first clustering high-quality sequenced epithelial versus non-epithelial cells, high-confidence tumor cell populations were identified. InferCNV was used to predict segmented copy-number alterations (CNAs), which were then used to determine arm-level aneuploidy at the single-cell level. Control comparisons of normal cells to normal cells showed zero arm-level aneuploidy, whereas a median of four aneuploid events were detectable in cancer cells. A heterogeneity analysis of high-grade tumor cells compared to low-grade tumor cells showed similar levels of cell-to-cell variation between cancer grades. Metastatic tumors potentially showed selection pressure with reduced cell-to-cell variation compared to cells from primary tumors. Minor cell populations with CNAs similar to metastatic cells were identified within the matched primary tumors. Taken together, these results provide a minimum estimate for single-cell aneuploidy in serous ovarian cancer and demonstrate the utility of single-cell sequencing for CNA analysis. | Authentic |
Text : Although extensive efforts have been made in recent decades to treat advanced gastric cancer with comprehensive therapy based on chemotherapy, effective anti-gastric cancer therapeutics are still lacking in the clinics. Therefore, potent novel anti-gastric cancer ways are greatly needed. Here, we explored hyperbaric oxygen treatment as a novel and effective adjuvant treatment method which has anti-gastric cancer effects when used together with melatonin. When performed together with MLT, HBO effectively inhibited tumorigenicity of gastric cancer through selectively inducing a robust tumor suppressive apoptosis response. Mechanistic studies revealed that the sensitizing effect of hyperbaric oxygen is due to decreased ratio of Bcl-2/Bax, increased level of p53, cleaved Caspase3, GRP78, CHOP, and LC3. These results give a vivid picture that classic apoptosis pathways including mitochondrial pathway, tumor suppressive endoplasmic reticulum stress (ERS), and autophagy are all involved in the process. From the preliminary results got from the current study, we identified that HBO sensitizes human gastric cancer cells to MLT-induced apoptosis through a variety of complicated molecular mechanisms. HBO may provide a novel candidate supplemental treatment method for further development of potential anti-gastric cancer therapeutics. The combination of HBO and MLT could be a promising treatment for advanced gastric cancer. | Authentic |
Text : Currently, new advancements in the area of nanotechnology opened up new prospects in the field of medicine that could provide us with a solution for numerous medical complications. Although a several varieties of nanoparticles is being explored to be used as nanomedicines, cerium oxide nanoparticles (CeO2 NPs) are the most attractive due to their biocompatibility and their switchable oxidation state (+3 and +4) or in other words the ability to act as prooxidant and antioxidant depending on the pH condition. Green synthesis of nanoparticles is preferred to make it more economical, eco-friendly, and less toxic. The aim of our study here is to formulate the CeO2 NPs (CeO2 NPs) using Morinda citrifolia (Noni) leaf extract and study its optical, structural, antibacterial, and anticancer abilities. Their optical and structural characterization was accomplished by employing X-ray diffractography (XRD), TEM, EDAX, FTIR, UV-vis, and photoluminescence assays. Our CeO2 NPs expressed strong antibacterial effects against Gram-positive S. aureus and S. pneumonia in addition to Gram-negative E. coli and K. pneumonia when compared with amoxicillin. The anticancer properties of the green synthesized CeO2 NPs against human acute lymphoblastic leukemia (ALL) MOLT-4 cells were further explored by the meticulous study of their ability to diminish cancer cell viability (cytotoxicity), accelerate apoptosis, escalate intracellular reactive oxygen species (ROS) accumulation, decline the mitochondria membrane potential (MMP) level, modify the cell adhesion, and shoot up the activation of proapoptotic markers, caspase-3, -8, and -9, in the tumor cells. Altogether, the outcomes demonstrated that our green synthesized CeO2 NPs are an excellent candidate for alternative cancer therapy. | Authentic |
Text : Toll‑like receptor 4 (TLR4), a key regulator of the innate immune system, is expressed not only in immune cells, but also in a number of cancer cells. A biological role for TLR4 in cutaneous squamous cell carcinoma (SCC), however, is unclear. In this study, we first examined TLR4 expression and localization in cases of SCC, actinic keratosis (AK) and Bowen's disease (BD) by immunohistochemistry. TLR4 expression was significantly higher in the SCC than in the AK or BD tissues. We then determined the TLR4 expression level in vivo, in 3 histological subtypes of SCC. TLR4 expression in poorly differentiated SCC was significantly lower compared with that of the moderately and well‑differentiated type. In addition, the CD44 immunoreactivity tended to be high in the cell membrane of poorly differentiated SCC. Of note, poorly differentiated SCC is a risk factor of unfavorable outcomes in affected patients. We then assessed the biological role of TLR4 in HSC‑1 and HSC‑5 SCC cells and HaCaT human keratinocytes. TLR4 knockdown by transfection with siRNA accelerated HSC‑1 and HaCaT cell migration and invasion compared to the control siRNA‑transfected cells. TLR4 knockdown resulted in an increased CD44 expression and in an enhanced filopodia protrusion formation, particularly in HSC‑1. On the whole, these results suggest that a reduced TLR4 expression enhances the malignant features in SCC cases and cultured SCC cell lines. TLR4 may thus play an anti‑tumor role in cutaneous SCC. | Authentic |
Text : To observe the short-term and long-term curative effects of partial hepatectomy on ruptured hemorrhage of primary liver cancer after transcatheter arterial embolization (TAE). A total of 150 patients with primary liver cancer treated in the hospital were enrolled as research objects between February 2018 and February 2021, including 75 cases undergoing TAE in the TAE group and the other 75 cases undergoing elective partial hepatectomy after TAE in the combination group. The surgical related indexes (leaving bed time, discharge time, success rate of hemostasis, lesion clearance rate), mean arterial pressure (MAP), heart rate (HR), hemoglobin, and liver function indexes (serum alpha-fetoprotein (AFP), albumin (ALB), total bilirubin (TBIL)) before and after treatment, postoperative complications, survival rate, and recurrence rate at 1 year after surgery between the two groups were compared. Compared with the TAE group, hospitalization time was shorter (P < 0.05), the success rate of hemostasis and lesions clearance rate were higher in the combination group (P < 0.05). After surgery, levels of HR and serum AFP were significantly decreased, while levels of MAP, hemoglobin, serum ALB, and TBIL were significantly increased in both groups. The levels of HR and serum AFP in the combination group were lower than those in the TAE group, while levels of MAP, hemoglobin, serum ALB, and TBIL were higher than those in the TAE group (P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P < 0.05). Compared with the TAE group, the recurrence rate was lower, and the survival rate was higher in the combination group at 1 year after surgery (P < 0.05). Partial hepatectomy can effectively improve hemostatic effect and liver function in ruptured hemorrhage of primary liver cancer after TAE, increase survival rate, and reduce postoperative recurrence rate. | Authentic |
Text : Pancreatic cancer (PC) is one of the most aggressive malignancies in humans. Despite advances in early detection and treatment of PC, the prognosis is still limited. LncRNA myocardial infarction-associated transcript (MIAT) is found abnormally expressed in a variety of cancers. However, the role of MIAT in PC is still unknown. This study aimed to explore whether MIAT was related to the progression of PC and the underlying mechanism. Bioinformatics analysis and luciferase reporter assay validated that miR-133 may target MIAT 3'-UTR. MIAT expression was found remarkably increased and miR-133 expression was significantly decreased in PC tissues and PC cell lines (PATU-8988, BxPC-3, PANC-1, SW1990 and AsPC-1 cells). PC patients with high MIAT level had poor prognosis than that with low MITA level. Besides that, PATU-8988 cells transfected with siMIAT and/or miR-133 inhibitor. The results exhibited that the inhibition of miR-133 expression reversed the inhibition effect of MIAT down-regulation in the growth, migration and invasion of PC cells. Moreover, tumor growth was tremendously suppressed in nude rats received injection of PATU-8988 cells transfected with siMIAT. Taken together, our results suggest that the interaction of MIAT and miR-133 play a role in the proliferation and metastasis of pancreatic carcinoma. | Counterfeit |
Text : Hepatocellular carcinoma (HCC) ranks fourth in global cancer mortality, accounting for 8.2% of all cancer deaths. Early detection of HCC has a significant impact on clinical outcomes. The aim of this study was to identify blood-based biomarkers which are HCC-specific. Comprehensive gene expression raw data of purified RNA of peripheral blood mononuclear cells (PBMC) was downloaded from GEO and was then analyzed. Differentially expressed genes (DEGs) in HCC were screened and the method of weighted gene co-expression network analysis was applied to identify candidate blood-based biomarkers associated with HCC. Three modules closely related to HCC were screened using WGCNA. Nuclear localization signal (NLS)-bearing protein import into nucleus biological process was the most significant enriched physiological process identified by MCODE, and 3 genes (DICER1, GMPS and NCOR1) were selected as biomarkers. In our study, three novel blood-based HCC-specific diagnostic biomarkers for human hepatocellular carcinoma were identified. These findings may contribute to the non-invasive detection of early HCC patients. | Authentic |
Text : This study was designed to investigate the role of miR-183 in modulating cell growth and apoptosis of tongue squamous cell carcinoma SCC25 cell line. Human squamous epithelial cell and squamous cell carcinoma cell line SCC25 was used, and miR-183 was inhibited. Cell growth, colony formation, and apoptotic rate, as well as the expression of caspase 3 and BCL-xL, were detected. Results showed that miR-183 was significantly overexpressed in the SCC25 cell line when compared with normal control. The miR-183 inhibitor reduced cell growth and colony formation, while the apoptosis percentage was significantly increased. The expression of activated caspase 3 and BCL-xL was obviously up- and downregulated in siRNA-transfected cells, respectively. In conclusion, miR-183 contributed to cell growth and proliferation, and suppressed cell apoptosis in SCC25 cells. Therefore, miR-183 might serve as a therapeutic target in tongue squamous cell carcinoma (TSCC). | Counterfeit |
Text : Hepatocellular carcinoma (HCC) is one of the most common human malignant diseases in the world, and the mechanisms underlying HCC carcinogenesis and progression need further investigation. MicroRNAs play important roles in the development of cancer, and miR-500a is suggested to be deregulated in some types of cancer. However, the underlying molecular mechanisms of miR-500a in HCC remain unknown. The expression of miR-500a in HCC was analyzed in The Cancer Genome Atlas (TCGA) database and examined in 33 pairs of HCC tissues and matched nontumor tissues. The correlation between miR-500a expression and prognosis of HCC patients was analyzed from the survival data in TCGA. The mechanism of miR-500a upregulation in HCC was detected using chromatin immunoprecipitation-quantitative real-time PCR. The roles of miR-500a in HCC development were examined using a cell counting kit-8 assay in vitro and growth of transplanted tumors in nude mice in vivo. Apoptosis of HCC was detected using Annexin V/propidium iodide staining. The expression of BH3-interacting death agonist (BID) protein was examined using western blot analysis. miR-500a expression was upregulated in HCC tissues, and high miR-500a expression was significantly correlated with the poor prognosis of HCC patients. Histone modifications in the promoter region of miR-500a may be responsible for its increased expression. Inhibition of miR-500a in HCC cell lines significantly promoted apoptosis, as well as inhibiting the proliferation of HCC cells and growth of transplanted tumors in nude mice. miR-500a directly targeted the 3' untranslated region of BID mRNA, and inhibition of miR-500a-promoted apoptosis was almost completely abolished by the administration of ABT-199 via the BID-mitochondria pathway. Our results suggest that histone modifications in the promoter region of miR-500a may be responsible for the increased expression of miR-500a in HCC, which promotes cancer progression by targeting BID, indicating that miR-500a may be a potential prognostic predictor and therapeutic target for HCC patients. | Authentic |
Text : Forkhead box R2 (FOXR2), a member of the FOX gene family, has not been very well investigated for its role in cancer. A recent study has shown that FOXR2 is highly expressed in breast cancer samples and is associated with poor prognosis. In addition, FOXR2 was identified as an oncogene in medulloblastoma. Nevertheless, whether FOXR2 plays a role in colorectal cancer (CRC) remains unclear. In the present study, we conducted several in vitro and in vivo studies to investigate the expression and effect of FOXR2 in CRC. The study results demonstrated that FOXR2 was upregulated in CRC tissues and cells. Downregulation of FOXR2 inhibited CRC cell proliferation, invasion, and the epithelial-mesenchymal transition (EMT) phenotype in vitro and also suppressed CRC cell growth and metastasis in vivo. Furthermore, downregulation of FOXR2 remarkably reduced the protein expression of Shh, Gli1, and Ptch1 in SW480 cells. Taken together, our data suggested that FOXR2 significantly promoted proliferation, invasion, and EMT of CRC cells. All these findings provided evidence for the role of FOXR2 as an oncogene in CRC development. | Authentic |
Text : MicroRNAs (miRNAs) are involved in the maintenance of the cancer stem cell (CSC) phenotype by binding to genes and proteins that modulate cell proliferation and/or cell apoptosis. In our study, we aimed to investigate the role of miR-1305 in the proliferation and self-renewal of liver CSCs (LCSCs) via the ubiquitin-conjugating enzyme E2T (UBE2T)-mediated Akt-signaling pathway. Differentially expressed genes in human hepatocellular carcinoma (HCC) were obtained by in silico analysis. The relationship between miR-1305 and UBE2T was verified by dual luciferase reporter gene assay. qRT-PCR and western blot analysis were performed to determine the expression of UBE2T, the Akt-signaling pathway, and stemness-related factors in LCSCs. In addition, miR-1305 disrupted the activation of the Akt-signaling pathway by targeting UBE2T, and, ultimately, it repressed the sphere formation, colony formation, and proliferation, as well as tumorigenicity of LCSCs. In summary, miR-1305 targeted UBE2T to inhibit the Akt-signaling pathway, thereby suppressing the self-renewal and tumorigenicity of LCSCs. Those findings may provide an enhanced understanding of miR-1305 as a therapeutic target to limit the progression of LCSCs. | Counterfeit |
Text : Anti-vascular endothelial growth factor (anti-VEGF) drugs have long been the only first-line treatment for advanced or unresectable hepatocellular carcinoma (HCC). Recently, the combination of bevacizumab (an anti-VEGF drug) and atezolizumab (an immune checkpoint blockade, ICB) has been proven to have superior efficacy over sorafenib. However, the complex association between VEGF signaling pathway and tumor immune microenvironment is still largely unknown. Here, we analyzed the RNA sequencing and clinical data of 365 HCC patients obtained from The Cancer Genome Atlas to investigate the potential correlation between VEGF signaling pathway and tumor immune microenvironment, including immune cell infiltration, 66 immune markers, genomic instability, and immune-related pathways. Our study revealed that VEGF signaling pathway score was positively correlated with immune cell infiltration and the expression profile of 66 immune markers. Enrichment analysis indicated that genes differentially expressed between two VEGF score subtypes were enriched in many immune-related Gene Ontology terms. Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs. | Authentic |
Text : Tumor targeting small molecular inhibitors are the most popular treatments for many malignant diseases, including cancer. However, the lower clinical response and drug resistance still limit their clinical efficacies. HGFK1, the first kringle domain of hepatocyte growth factor, has been defined as a potent anti-angiogenic factor. Here, we aimed to develop and identify novel nanoparticles-PH1/pHGFK1 as potential therapeutic agents for the treatment of renal cell carcinoma (RCC). We produced a novel cationic polymer-PH1 and investigated the anti-tumor activity of PH1/pHGFK1 nanoparticle alone and its combination therapy with sorafenib in RCC cell line xenografted mice model. Then, we figured out its molecular mechanisms in human RCC cell lines in vitro. We firstly demonstrated that intravenous injection of PH1/pHGFK1 nanoparticles significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice, as well as synergistically enhanced anti-tumor activities of sorafenib. Furthermore, we elucidated that recombinant HGFK1 improved sorafenib-induced cell apoptosis and arrested cell cycle. In addition, HGFK1 could also decrease sorafenib-induced autophagy and stemness via blockading NF-κB signaling pathway in RCC both in vitro and in vivo. HGFK1 could inhibit tumor growth, synergistically enhance anti-tumor activities of sorafenib and reverse its drug resistance evolution in RCC. Our results provide rational basis for clinical application of sorafenib and HGFK1 combination therapy in RCC patients. | Authentic |
Text : The Hippo signaling pathway is associated with cell proliferation and organ size, and its transcriptional coactivator Yes-associated protein (YAP), emerges as a crucial oncoprotein in multiple cancers. It was increasingly recognized that nonreceptor tyrosine phosphatase 14 (PTPN14) was relevant to the cell membrane and cytoskeleton, and had a critical effect on cell adhesion, growth, and actin cytoskeleton organization. Furthermore, PTPN14 was also certified to operate the translocation and phosphorylation of YAP. The present experiment was aimed to explore the impact of PTPN14 on gastric cancer (GC) cell proliferation and migration through regulating the phosphorylation of YAP. The pEGFP-N1-PTPN14 recombinant plasmid was stably transfected into three differentiation degrees GC cell lines, including MKN-28, SGC-7901, and BGC-823. Quantitative reverse transcription-polymerase chain reaction and Western blot assay were performed to analyze the messenger RNA (mRNA) and protein levels. The proliferative and migratory capacity of cells was appraised by Cell Counting Kit-8 assay and transwell chamber. Compared with the normal control and vector transfection group, the capacity of these three cell lines, which transfected with the pEGFP-N1-PTPN14 to proliferate and migrate in vitro was increased obviously (P < .05). There was no YAP mRNA detected in MKN-28 cell line. Meanwhile, after transfecting the pEGFP-N1-PTPN14 plasmid, the mRNA level of YAP in SGC-7901 was reduced (P < .05), and it was increased in BGC-823 (P < .05). The YAP protein level in SGC-7901 and BGC-823 has no apparent transformation by transfecting, but the protein level of phospho-Ser127 YAP and phospho-Ser397 YAP is upregulated (P < .05). PTPN14 could enhance the proliferative and migratory ability of GC cells by promoting the YAP phosphorylation in the Hippo signaling pathway. Taken together, PTPN14 might be involved in the occurrence and development of GC and become a molecular regulator to treat GC. | Authentic |
Text : Cervical cancer is the fourth most common malignancy in women worldwide and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The dysregulation of genes plays a significant role in cancer. In the present study, we screened out differentially expressed genes (DEGs) of CESC in the GSE63514 data set from the Gene Expression Omnibus database. An integrated bioinformatics analysis was used to select hub genes, as well as to investigate their related prognostic signature, functional annotation, methylation mechanism, and candidate molecular drugs. As a result, a total of 1907 DEGs were identified (944 were upregulated and 963 were downregulated). In the protein-protein interaction network, three hub modules and 30 hub genes were identified. And two hub modules and 116 hub genes were screened out from four CESC-related modules by the weighted gene coexpression network analysis. The gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. Genes with a significant prognostic value were found by prognostic signature analysis. And there were five genes (EPHX2, CHAF1B, KIAA1524, CDC45, and RMI2) identified as significant CESC-associated genes after expression validation and survival analysis. Among them, EPHX2 and RMI2 were noted as two novel key genes for the CESC-associated methylation and expression. In addition, four candidate small molecule drugs for CESC (camptothecin, resveratrol, vorinostat, and trichostatin A) were defined. Further studies are required to explore these significant CESC-associated genes for their potentiality in diagnosis, prognosis, and targeted therapy. | Authentic |
Text : This study focuses on the evaluation of the clinical utility of PET-CT imaging in peritoneal metastases and colorectal cancer. One hundred patients with colorectal peritoneal metastases, who underwent whole-body PET-CT imaging from January 2015 to December 2019, were selected as the experimental group, and 20 healthy individuals were selected as the control group. The SUVmax of the two groups of patients was 5.73 ± 3.84 and 2.70 ± 2.32, respectively, and the difference was statistically significant. The SUVmax AUC was 0.720, and the AUC of serum AFP, CEA, CA125, and CA199 were 0.596, 0.677, 0.642, and 0.696, respectively. Conclusion. 100 patients with colorectal and peritoneal metastatic cancer underwent PET/CT examination. The follow-up or other imaging examinations confirmed the diagnosis. Analysis of the ROC curve in this study found that with a peritoneal SUVmax> 3.2 as the diagnostic index for colorectal peritoneal metastatic cancer, the sum of sensitivity and specificity reached the maximum. | Authentic |
Text : Diffuse-type gastric cancer (DGC), for which Helicobacter pylori infection is a causal factor, is associated with poor prognosis among young women, possibly due to female hormones such as estrogen. We aimed to identify the carcinogenesis induced by estrogen and H. pylori in DGC. We screened and selected estrogen receptor alpha (ERα)-positive (MKN45) and ERα-negative (SNU5) DGC cell lines. H. pylori strain 60190 and its isogenic mutant strain lacking cytotoxin-associated gene A (60190ΔCagA) were used to infect MKN45 cells. And the cytotoxin-related gene A (CagA) cDNA which was cloned into pSP65-SR-HA (cagA-pSP65SRa) vector was used to transfect MKN45 cells. Tumor samples were used for DGC organoid culture. In MKN45 cells, we found that estradiol promotes epithelial-mesenchymal transition (EMT) and stemness phenotypes via HOTAIR expression. These effects were further enhanced by the addition of CagA secreted by H. pylori but were reversed by co-treatment with fulvestrant (ICI 182,780), a selective ER degrader. We also validated the effect of estrogen on DGC organoids. ERα expression was associated with tumor invasion and HOTAIR expression in DGC patients with overt H. pylori infection. These findings may explain the rapid DGC progression in young women with physiologically high levels of estrogen and suggest that fulvestrant with ovarian function suppression could serve as a tumor-suppressive agent in premenopausal patients with DGC. | Authentic |
Text : Cervical cancer (CC) is a primary gynecological malignancy worldwide. Cancer stem cells (CSCs) possess enhanced tumor-initiating and self-renewing abilities. MicroRNAs (miRNAs) play essential roles in CSCs' tumorigenesis. This study investigated the effects of miR-146a on CSCs' tumorigenesis and invasion. Tumorsphere cells (TCs) were enriched from the HeLa cell line. Real-time PCR, Western blots, ALDH assays, colony formation and invasion assays, luciferase reporter assays and the Xenograft mouse model were used to determine the underlying mechanism of CC. The results showed that TCs displayed higher ALDH activity and miR-146a was upregulated in differentiated TCs. Moreover, miR-146a inhibitor increased colony formation and cell invasion in TCs while miR-146a mimics displayed the opposite roles. An inverse relationship between miR-146a and VEGF expression was found in TCs and the luciferase reporter assay revealed that VEGF was a direct target of miR-146a. Inhibition of VEGF reversed the effects of miR-146a inhibitor on TCs. The activated CDC42/PAK1 signaling was associated with TCs' tumorigenesis and invasion. Furthermore, miR-146a inhibitor-treated TCs promoted tumor growth in nude mice. Altogether, the results suggest that miR-146a modulated TCs' tumor formation and invasion and was associated with VEGF/CDC42/PAK1 signaling. This study provided insight into developing new therapeutic strategies for CC. | Authentic |
Text : Garcinol, a natural histone acetyltransferase inhibitor, has been reported to exhibit significant anti-proliferative activity in various cancer cell types. However, no information is available about the anti-cancer effects of garcinol on gallbladder carcinoma cells (GBC). In this study, GBC cells (GBC-SD and NOZ) were treated by garcinol and subjected to Cell Counting Kit-8 (CCK-8), and GBC-SD cells were selected for further transwell chamber assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Our results indicated that garcinol could significantly inhibit the growth of GBC cells in a dose- and time-dependent manner. It also inhibited the invasion of GBC-SD cells in a dose-dependent manner. Garcinol treatment decreased the activity of matrix metalloproteinase 2 (MMP2) and MMP9 by the downregulation of mRNA levels, and these two enzymes are critical to tumor invasion. Treatment with garcinol also decreased Stat3 and Akt activation in GBC-SD cells. Taken together, the effects of garcinol on GBC-SD cells may be associated with the suppression of Stat3 and Akt signaling pathways, which may contribute to inhibiting their downstream targets such as mRNA levels of MMP2 and MMP9. | Authentic |
Text : Ischemic stroke is a refractory disease caused by cerebral ischemic injury, which results in brain dysfunction. This study intends to investigate the effects of microRNA-212 (miR-212) on the recovery function and vascular regeneration of endothelial progenitor cells (EPCs) by inactivation of the Notch signaling pathway by binding to matrix metallopeptidase 9 (MMP9) in mice with ischemic stroke. According to the results of database retrieval systems and data analysis, MMP9 was predicted as a gene related to ischemic stroke and miR-212 is a potential regulating mRNA of MMP9. All 72 healthy adult C57BL6 mice were selected for middle cerebral artery occlusion (MCAO) establishment. Cerebral infarction was observed under triphenyltetrazolium chloride staining. A series of inhibitors, activators, and siRNAs were introduced to the verified regulatory functions for miR-212 governing MMP9 in ischemic stroke. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and tube-forming ability by tubule formation test. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were used to detect the expressions of miR-212, MMP9, Hes-1, and Notch-1. The corresponding results demonstrated that the area of cerebral infarction and the number of neuronal necrosis increased in the MCAO group in contrast to the sham group. Meanwhile, upregulation of miR-212 or downregulation of MMP9 decreases the expressions of MMP9, Hes-1 Notch-1, increases cell proliferation and tube-forming ability and improves the pathological conditions of EPCs. Our study suggests that miR-212 promotes recovery function and vascular regeneration of EPCs through negative regulation of the Notch signaling pathway via downregulating expression of MMP9, thus provides a clinical theoretical basis for ischemic stroke therapy. | Counterfeit |
Text : LIM homeobox domain 6 (LHX6) is emerging as a critical regulator in carcinogenesis and tumor progression. The previous study has reported the expression and function of LHX6 in breast cancer (BC). However, its mechanism underlying BC metastasis remains largely unclear. This study aimed to investigate the related mechanisms of the tumor-suppressive role of LHX6 in BC. Quantitative Real-time PCR (qRT-PCR) and Western blotting were used to determine LHX6 mRNA levels and protein expressions in BC tissues and cell lines. LHX6 protein expression was also analyzed in BC tissues and matched normal breast tissues using immunohistochemistry (IHC). The biologic functions of LHX6 in BC were explored by CCK-8 assay, colony formation assay, and transwell assays in vitro. Finally, we investigated the effect of LHX6 up-regulation on PI3K/AKT/mTOR pathway by Western blot. Our results showed that LHX6 was lowly expressed at the mRNA and protein level in BC cancer tissues and cell lines. Ectopic expression of LHX6 in MDA-MB-231 and T-47D suppressed cell growth, migration, and invasion. Mechanistically, our further investigations revealed that the upregulation of LHX6 inhibited the activation of the PI3K/Akt/mTOR signaling pathway. We firstly provided evidence that LHX6 exerted its anti-tumor function on BC via suppressing activation of the PI3K/Akt/mTOR signaling, which eventually inhibited the progression of BC. | Authentic |
Text : Myocardial ischemia is a serious disease which threatens human's life. Lentinan (LEN) possesses multiple biological properties: anticancer, antibacterial, antiviral and antioxidant effects. Our study investigated the effects of LEN on hypoxia-stimulated cardiomyocytes and the underlying mechanism. Primary neonatal rat ventricular cardiomyocytes (PNCM) were isolated from neonate rat pups. PNCM and H9c2 cells were stimulated by hypoxia and treated by LEN. Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. Moreover, apoptotic factors were examined by western blot. Phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) and β-catenin pathways related proteins were analyzed by western blot. Furthermore, the expression of microRNA-22 (miR-22) was detected by qRT-PCR. Altered expression of miR-22 and silenced information regulator 1 (Sirt1) was achieved by transfection. The relationship between miR-22 and Sirt1 was verified by luciferase assay. We found that LEN promoted cell viability and decreased apoptosis which led to the contrary results with what hypoxia induced. Moreover, LEN decreased the ratio of Bax to Bcl-2 and the level of cleaved caspase-3, as well as activated PI3K/AKT and β-catenin. LEN decreased the expression of miR-22 which was upregulated by hypoxia. miR-22 overexpression broken the promoting effects led by LEN. Moreover, Sirt1 was verified to be a target of miR-22. Silence of Sirt1 led to the opposite results with LEN. In conclusion, LEN relieved hypoxia-induced cellular injuries evidenced by increasing viability and decreasing apoptosis via down-regulation of miR-22, which was accompanied by activation of PI3K/AKT and β-catenin pathways. Highlights Lentinan alleviates hypoxia-induced injuries of PNCM and H9c2 cells; microRNA-22 expression is decreased by lentinan; Lentinan reduces hypoxia-induced injury by microRNA-22 downregulation; Lentinan regulates PI3K/AKT and Wnt/β-catenin by regulation of microRNA-22/Sirt1. | Counterfeit |
Text : Using tumors containing high concentrations of hydrogen peroxide to design nanozymes is a new and effective strategy, and vanadium-based nanomaterials receive increasing attention. In this paper, four kinds of vanadium oxide nanozymes with different valences of vanadium are synthesized by a simple method to verify the effect of valence on enzyme activity. Vanadium oxide nanozyme-III (Vnps-III) with a low valence of vanadium (V4+) exhibits good peroxidase (POD) and oxidase (OXD) activities, which can effectively produce reactive oxygen species (ROS) in the tumor microenvironment for tumor treatment. In addition, Vnps-III can also consume glutathione (GSH) to reduce ROS consumption. Vanadium oxide nanozyme-I (Vnps-I) containing a high valence of vanadium (V5+) has catalase (CAT) activity, which can catalyze hydrogen peroxide (H2O2) into oxygen (O2), which is beneficial to alleviate the hypoxic environment of solid tumors. Finally, a vanadium oxide nanozyme with both trienzyme simulation activity and GSH consumption ability was screened out by adjusting the ratio of V4+ to V5+ in vanadium oxide nanozymes. In cell and animal experiments, we successfully demonstrate that vanadium oxide nanozymes have excellent antitumor ability and high safety, which may bring great potential for clinical cancer treatment. | Authentic |
Text : Gastric cancer is still among the leading causes of cancer deaths worldwide. Despite the improvements in diagnostic methods, the status of early detection has not been achieved so far. Early diagnosis of gastric cancer may significantly improve the cure rate of patients. Therefore, a new diagnostic method is needed. In this study, subtractive SELEX was performed to screen gastric cancer serum-specific DNA aptamers by using gastric cancer serum and normal serum as the target and negative serum, respectively. Four highly specific aptamers generated for gastric cancer serum, Seq-3, Seq-6, Seq-19 and Seq-54, were developed using whole-serum subtractive SELEX technology with K d of 128 ± 26.3 nM, 149 ± 23.6 nM, 232 ± 44.2 nM, 202 ± 25.6 nM, respectively. These generated aptamers showed higher specificities toward their target serum by differentiating normal serum but closely related other cancer serums. The selected four high affinity DNA aptamers were further applied to the development based on qPCR method for the early detection of gastric cancer. In addition, we performed MALDI-TOF MS followed by secondary peptide sequencing MS analysis for the identification of the aptamer binding proteins. Among these potential biomarkers, APOA1, APOA4, PARD3, Importin subunit alpha-1 showed a relatively high score probability. Therefore, these four ssDNA aptamers generated in our study could be a promising molecular probe for gastric cancer diagnosis. | Authentic |
Text : Cutaneous squamous cell carcinoma (CSCC), an epidermal keratinocyte-derived skin tumor, is one of the most leading causes of cancer-associated morbidity and mortality worldwide. Long noncoding RNAs have emerged as key regulators of tumor development and progression. Recent studies have identified LINC00319, a long intergenic noncoding RNA, as an oncogene in lung cancer. However, the biological role of LINC00319 in CSCC remains largely unknown. The current study aimed to explore the role of LINC00319 in CSCC and uncover the molecular mechanisms. In current study, we found that LINC00319 was significantly upregulated in both CSCC tissues and cell lines. Besides, the χ2 test showed that increased expression of LINC00319 was associated with larger tumor size, advanced TNM stage, and lymphovascular invasion. Gain-of-function and loss-of-function approaches were applied to investigate the effects of LINC00319 on CSCC cells. Functional studies demonstrated that LINC00319 promoted CSCC cell proliferation, accelerated cell cycle progression, facilitated cell migration and invasion, and inhibited cell apoptosis. Mechanistic studies revealed that LINC00319 exerts its oncogenic functions in CSCC via miR-1207-5p-mediated regulation of cyclin-dependent kinase 3. Taken together, upregulation of LINC00319 implies a potential link with poor prognosis and reflects CSCC progression. Collectively, this study may provide some evidence for LINC00319 as a candidate target in CSCC treatment. | Authentic |
Text : Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib. A search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR), disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety. A total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%), disease control rate 88% (95% CI: 82% to 94%), progression-free survival 9.36 months (95% CI: 7.38% to 11.34%), and intracranial ORR 52% (95% CI: 45% to 59%). ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%), and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%). The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18%) and anemia (25%), were even higher than with the first-generation ALK inhibitor crizotinib. Generally, alectinib is a drug with preferable efficacy and tolerable adverse effects, and it is suitable for the treatment of intracranial metastases. | Authentic |
Text : Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population. | Authentic |
Text : Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play pivotal roles in the processes of cancer occurrence, progression, and treatment. FAM83A-AS1 is a novel onco-lncRNA involved in various cancers. Nevertheless, the biological function and underlying mechanism of FAM83A-AS1 in lung adenocarcinoma (LUAD) remain largely unclear. In this study, we found FAM83A-AS1 to be upregulated in LUAD tissues and closely associated with tumor size, lymph node metastasis, and TNM stage. In addition, high FAM83A-AS1 expression correlated positively with a poor prognosis. Functional investigation revealed that FAM83A-AS1 promotes LUAD cell proliferation, migration, invasion and the epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Mechanistically, FAM83A-AS1 functions as an endogenous sponge of miR-150-5p by directly targeting it, removing inhibition of MMP14, a target of miR-150-5p. Furthermore, rescue assays demonstrated that FAM83A-AS1 enhances cell migration, invasion and EMT by modulating the miR-150-5p/MMP14 pathway. Collectively, we conclude that the novel FAM83A-AS1/miR-150-5p/MMP14 axis regulates LUAD progression, suggesting an innovative therapeutic strategy for this cancer. | Authentic |
Text : We conducted a meta-analysis to comprehensively evaluate the correlations of ezrin expression with pathological characteristics and the prognosis of osteosarcoma. The MEDLINE (1966-2013), the Cochrane Library Database, EMBASE, CINAHL, Web of Science (1945-2013), and the Chinese Biomedical Database were searched without language restrictions. Meta-analyses conducted using STATA software were calculated. Ten studies met the inclusion criteria, including 459 patients with osteosarcoma. Meta-analysis results illustrated that ezrin expression may be closely associated with the recurrence of osteosarcoma or metastasis in osteosarcoma. Our findings also demonstrated that patients with grade III-IV osteosarcoma showed a higher frequency of ezrin expression than those with histological grade I-II osteosarcoma. Furthermore, we found that patients with positive expression of ezrin exhibited a shorter overall survival than those with negative ezrin expression. The results also indicated that positive ezrin expression was strongly correlated with poorer metastasis-free survival. Nevertheless, no significant relationships were observed between ezrin expression and clinical variables (age and gender). In the current meta-analysis, our results illustrated significant relationships of ezrin expression with pathological characteristics and prognosis of osteosarcoma. Thus, ezrin expression could be a promising marker in predicting the clinical outcome of patients with osteosarcoma. | Counterfeit |
Text : Epigenetic readers are specific proteins which recognize histone marks and represents the underlying mechanism for chromatin regulation. Histone H3 lysine methylation is a potential epigenetic code for the chromatin organization and transcriptional control. Recognition of histone methylation is achieved by evolutionary conserved reader modules known as chromodomain, identified in several proteins, and is involved in transcriptional silencing and chromatin remodelling. Genetic perturbations within the structurally conserved chromodomain could potentially mistarget the reader protein and impair their regulatory pathways, ultimately leading to cellular chaos by setting the stage for tumor development and progression. Here, we report the structural conservations associated with diverse functions, prognostic significance and functional consequences of mutations within chromodomain of human proteins in distinct cancers. We have extensively analysed chromodomain containing human proteins in terms of their structural-functional ability to act as a molecular switch in the recognition of methyl-lysine recognition. We further investigated the combinatorial potential, target promiscuity and binding specificity associated with their underlying mechanisms. Indeed, the molecular mechanism of epigenetic silencing significantly underlies a newer cancer therapy approach. We hope that a critical understanding of chromodomains will pave the way for novel paths of research providing newer insights into the designing of effective anti-cancer therapies. | Authentic |
Text : β-elemene, a compound extracted from Curcuma wenyujin plant, exhibits anticancer activity in many cancer types. However, the detailed mechanism by which β-elemene inhibits growth of nasopharyngeal carcinoma (NPC) cells remains unknown. We showed that β-elemene reduced phosphorylation of signal transducer and activator of transcription 3 (Stat3), and protein expressions of DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2). Exogenously expressed Stat3 antagonized the effect of β-elemene on DNMT1 and EZH2 expressions. Furthermore, overexpressions of DNMT1 and EZH2 reversed the effect of β-elemene on phosphorylation of Stat3 and cell growth inhibition. Intriguingly, exogenously expressed DNMT1 overcame β-elemene-inhibited EZH2 protein expression and promoter activity. On the contrary, silencing of EZH2 and DNMT1 genes feedback strengthened the effect of β-elemene on phosphorylation of Stat3. Consistent with this, β-elemene inhibited tumor growth, phosphorylation of Stat3, expressions of DNMT1 and EZH2 in a mouse xenograft model. Collectively, this study shows that β-elemene inhibits NPC cell growth via inactivation of Stat3, and reduces DNMT1 and EZH2 expressions. The interplay of DNMT1 and EZH2, and the mutual regulations among Stat3, EZH2 and DNMT1 contribute to the overall responses of β-elemene. This study uncovers a novel mechanism by which β-elemene inhibits growth of NPC cells. | Authentic |
Text : "Orphan" cytochromes are a new group of P450 cytochromes without a fully recognized biological role. The expression of these CYPs in tumors is higher than that in normal tissues, which makes them attractive as chemopreventive and/or therapeutic targets. In this study, we compared the effect of synthetic methoxy stilbenes and resveratrol on the expression of two orphan cytochromes, CYP2S1 and CYP2W1, in breast cancer cells. Breast cancer cells, lines MCF7 and MDA-MB-231, were treated for 72 h with tested compounds. The expression of CYP2S1 and CYP2W1 was evaluated at the transcript and protein levels by RT-PCR and Western blot, respectively. The constitutive expression of both isoforms was confirmed at the mRNA and protein levels. CYP2S1 and CYP2W1 showed higher expression in MDA-MB-231 cells. In MCF7 cells treated with stilbenes, the expression of both CYPs was increased at the mRNA level, whereas at the protein level this effect was confirmed for CYP2S1 alone. In contrast, in estrogen receptor-negative MDA-MB-231 cells treated with stilbenes, the expression of both CYPs decreased, but mostly at the transcript level. The results of the present study confirmed the constitutive expression of CYP2S1 and CYP2W1 in breast cancer cells, although their relatively low level of expression suggests that they may be less involved in the transformation of therapeutic agents in these types of tumors. Stilbenes, particularly 3MS and 4MS, can modulate the expression of "orphan" CYPs more efficiently than resveratrol. | Authentic |
Text : Laryngeal squamous cell carcinoma (LSCC) is a very common neoplasm of the head and neck in the world. Long noncoding RNAs play key roles in cell infiltration, fate, apoptosis, and invasion. However, the functional role and expression of LINC00339 remains unclear in LSCC. In this study, we showed that the expression level of LINC00339 was upregulated in LSCC tissues and cell lines. LINC00339 silencing suppressed the proliferation, invasion, and epithelial-mesenchymal transition (EMT) progression of LSCC cells. In addition, we showed that LINC00339 acted as a sponge of miR-145, and LINC00339 silencing promoted the expression of miR-145 in Hep2 cell. Furthermore, the expression of miR-145 was lower in LSCC tissues than in their paired normal samples and the miR-145 expression level was negatively correlated with LINC00339 expression in LSCC tissues. The knockdown of miR-145 promoted the proliferation, invasion, and EMT progression of LSCC cells. Finally, we indicated that LINC00339 silencing inhibited the proliferation, invasion, and EMT progression of LSCC cells by suppressing the miR-145 expression. These data suggested that LINC00339 acted as an oncogene in the development of LSCC, partly by regulating the miR-145 expression. | Authentic |
Text : Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions. While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells. Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches. | Authentic |