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Text : The microRNA (miR)-200 family has been found to be involved in the process of mesenchymal-epithelial transition during renal development. Deregulation of miR-200c has been suggested to be involved in clear cell renal cell carcinoma (ccRCC). However, the precise role of miR-200c in the regulation of ccRCC metastasis has not been previously reported. In the present study, it was observed that miR-200c was frequently downregulated in ccRCC tissue compared with matched adjacent normal tissue. The expression of miR-200c was additionally reduced in ccRCC cell lines when compared with levels in normal renal cells. The DNA demethylation drug 5-Aza-2'-deoxycytidine (Aza) was used to treat several ccRCC cell lines, and it was observed that the expression of miR-200c was significantly increased following Aza treatment. Furthermore, treatment with Aza markedly inhibited ccRCC cell invasion and migration, while treatment with miR-200c inhibitor significantly enhanced invasion and migration of ccRCC cells. In addition, Aza treatment significantly promoted expression of E-cadherin and inhibited the expression of N-cadherin, while the inhibition of miR-200c downregulated E-cadherin and upregulated the expression of N-cadherin, suggesting that miR-200c has a suppressive role in epithelial-mesenchymal transition (EMT) of ccRCC cells. In conclusion, it was suggested that demethylation drug Aza-induced upregulation of miR-200c may inhibit migration, invasion and EMT in ccRCC cells. | Counterfeit |
Text : Peritoneal dissemination is the most common condition of metastasis in gastric cancer. The survival duration of a patient with advanced stage gastric cancer, may be improved by gene therapy. In this study, we used an oncolytic adenovirus vector (Ad/TRAIL-E1) that expresses both the TRAIL and E1A genes under the control of a tumor-specific promoter. We evaluated the anti-tumor effect of Ad/TRAIL-E1 on gastric cancer cells in vitro, as well as in vivo in a xenograft peritoneal carcinomatosis mouse model. Our data showed that Ad/TRAIL-E1 induced TRAIL-mediated apoptosis in gastric cancer cell lines, but not in the normal cell lines. In addition, Ad/TRAIL-E1 significantly inhibited peritoneal metastasis and prolonged the survival of mice without treatment-related toxicity. Therefore, tumor-specific TRAIL expression from an oncolytic adenovirus vector may provide a novel therapeutic approach for the treatment of advance stage gastric cancer with peritoneal dissemination. | Authentic |
Text : To explore the imaging diagnostic value of primary solitary bone tumor and tumor-like lesion of iliac crest. A total of 156 patients with primary solitary bone tumors and tumor-like lesions of the iliac bone treated in our hospital were selected, and the patients were diagnosed by X-ray, CT, and MRI. Sexual analysis of single diagnostic and combined diagnostic value was carried out. Round high-density shadow, soft tissue mass shadow, soft tissue mass, right intestinal tube, and bladder obvious pressure were observed. The detection rates of giant cell tumor of bone, myeloma, osteochondroma, chondroma, eosinophilic granuloma, osteosarcoma, fibrous dysplasia, and Hodgkin lymphoma were 34.6%, 12.8%, 11.5%, 10.3%, 7.7%, 6.4%, 3.8%, and 2.6%, and the differences were statistically significant (P < 005); X-ray, CT, MR single diagnostic comparison, three methods joint diagnostic missed diagnosis rate and misdiagnosis rate, higher detection rate (P < 0.05); combined with X-ray, CT, MR single diagnosis, three methods joint diagnosis sensitivity, specificity, accuracy, statistical significance (P < 0.05); comparison with X-ray, CT, MR single diagnosis, three methods jointly diagnosed positive predictive value, negative predictive value higher, difference statistics significance (P < 0.05); there is a significant difference in the near-end, backbone, and distal detection rate of different bone tumors and tumor lesions, including the humerus and tibia. There is a statistical significance of the detection rate, and the difference isP < 0.05. X-ray plays an important role in the diagnosis of primary solitary bone tumor and tumor-like lesion of iliac crest and is the first choice in clinical diagnosis. In the diagnosis of tumor disease, range, and soft tissue mass, MRI and CT diagnostic value can provide effective theoretical basis for patient clinical treatment. Therefore, the appropriate diagnostic method should be selected according to the specific situation of the patient, so that the efficiency of the clinical feature is improved. | Authentic |
Text : Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer. Tumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p. We found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497-5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro. Our work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation. | Authentic |
Text : Circular RNAs (circRNAs) have been demonstrated to involve in the development of various cancers. This study aimed to investigate the functions of circ_0001742 on regulating tongue squamous cell carcinoma (TSCC) development and the underlying mechanisms. The expression of circ_0001742, miR-431-5p and activating transcription factor 3 (ATF3) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of epithelial-mesenchymal transition (EMT)-related proteins and ATF3 were measured by Western blot analysis. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were used to evaluate cell proliferation and apoptosis. Besides, Cell migration and invasion were assessed by transwell assay. The relationships between circ_0001742 and miR-431-5p, miR-431-5p and ATF3 were predicted by online software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and pull-down assay. The expression of circ_0001742 was upregulated in TSCC tissues and cells. Knockdown of circ_0001742 inhibited proliferation, migration, invasion and EMT and induced apoptosis in TSCC cells. Then, miR-431-5p was identified as a target of circ_0001742, and knockdown of miR-431-5p reversed the effects of circ_0001742 knockdown on proliferation, apoptosis, migration, invasion and EMT of TSCC cells. Moreover, miR-431-5p could bind to ATF3, and overexpression of ATF3 rescued the effects mediated by miR-431-5p in TSCC cells. In addition, circ_0001742 regulated ATF3 expression through miR-431-5p. Our results demonstrated that circ_0001742 plays a tumor-promoting effect in TSCC cells by serving as a competing endogenous RNA (ceRNA) to regulate miR-431-5p/ATF3 axis, which might provide a potential therapeutic target for TSCC. | Authentic |
Text : Prostate stem cell antigen (PSCA) was originally identified as a gene that is overexpressed in prostate cancer, and correlates with prostate cancer progression and prognosis. Recently, a significant association has been identified between the PSCA rs2294008 (C>T) polymorphism and the risk of developing bladder cancer. Therefore, the present study investigated the different expression levels of PSCA mRNA in transitional cell carcinoma (TCC) of the bladder and normal bladder tissue. Furthermore, the association between PSCA mRNA expression levels in TCC and different rs2294008 (C>T) genotypes and various clinicopathological features, including tumor stage and grade, were evaluated. Reverse transcription-quantitative polymerase chain reaction was performed on 80 TCC samples and 38 samples of normal bladder urothelium from TCC patients who underwent transurethral resection of bladder tumor or radical cystectomy at the Beijing Friendship Hospital (Beijing, China) between September 2010 and May 2011. Genomic DNA was extracted from tumor tissue and sequenced to determine the rs2294008 (C>T) genotype. PSCA mRNA expression was detected in all samples (100%); however, tumor samples exhibited significantly higher PSCA expression levels compared with the normal urothelium samples (P=0.038). PSCA mRNA expression was positively correlated with the histological grade of the tumor (G1-2 vs. G3; P=0.001); however, no significant difference was detected between patients with superficial (Ta or T1) and muscle-invasive (≥pT2) tumors (P=0.250). Thus, PSCA mRNA expression levels were associated with TCC and tumor histological grade, but not the tumor stage. Additionally, PSCA mRNA expression levels were significantly higher in T allele carriers compared with CC homozygous patients (P=0.001), indicating that the presence of the T allele may increase PSCA mRNA expression. Therefore, rs2294008 (C>T) may be associated with the biological properties of TCC and, thus, future research should focus on the physiological function of PSCA and the mechanism of rs2294008. | Authentic |
Text : This study aimed to elucidate how microRNA27a-3p (miR-27a-3p) modulates the Wnt/β-catenin signaling pathway to promote the epithelial-mesenchymal transition (EMT) in oral squamous carcinoma stem cells (OSCSCs) by targeting secreted frizzled-related protein 1 (SFRP1). Flow cytometry was used to sort OSCSCs from the SCC-9 and Tca8113 cell lines. The OSCSCs were randomly assigned into the miR-27a-3p inhibitors group, the miR-27a-3p inhibitors-NC group, the si-SFRP1 group, the si-SFRP1 + miR-27a-3p inhibitors group and the blank group. A luciferase reporter, immunofluorescence and Transwell assays were performed to detect luciferase activity, SFRP1, and cell migration and invasion, respectively. The mRNA expression of miR-27a-3p, SFRP1 and EMT markers (E-cadherin, N-cadherin, vimentin and ZEB1) were detected using qRT-PCR. The protein expression of SFRP1, EMT markers and the proteins of the Wnt/β-catenin signaling pathway was detected by Western blotting. OSCSCs showed up-regulated miR-27a-3p, Wnt/β-catenin signaling pathway-related proteins, vimentin, N-cadherin and ZEB1 and down-regulated SFRP1 and E-cadherin. MiR-27a-3p targeted SFRP1. Down-regulated miR-27a-3p resulted in increased E-cadherin and SFRP1 but decreased vimentin, N-cadherin, ZEB1, the Wnt/β-catenin signaling pathway-related proteins, and invasive and migratory cells. Silenced SFRP1 reversed this effect. We found that miR-27a-3p modulated the Wnt/β-catenin signaling pathway to promote EMT in OSCSCs by down-regulating SFRP1. | Counterfeit |
Text : Signal transducer and activator of transcription 3 (STAT3) is an important protein in Janus kinase (JAK)-STAT signaling pathway, and can facilitate expression of Bcl-2 and Cyclin D1 gene, thus playing a role in tumor pathogenesis. Bioinformatics analysis revealed targeted binding sites between mircroRNA-124 (miR-124) and 3'-UTR of STAT3 mRNA. This study aims to investigate the role of miR-124 in regulating STAT3 expression and proliferation, cycle, apoptosis and invasion of prostate cancer cells. Dual luciferase reporter gene assay demonstrated targeted correlation between miR-124 and STAT3. Expression of miR-124, STAT3, p-STAT3, Bcl-2 and Cyclin D1 was compared between normal human prostate epithelial cell RWPE-1 and prostate cancer cell DU145. In vitro cultured DU145 cells were treated with miR-124 mimic and/or si-STAT3, to compare expression of STAT3, phosphorylated STAT3 (p-STAT3), B-cell lymphoma-2 (Bcl-2) and Cyclin D1. Flow cytometry detected cell apoptosis and cycle, followed by clonal formation and transwell assay to test malignant proliferation and cell invasion. Targeted regulation existed between miR-124 and STAT3. Comparing to RWPE-1, DU145 cells had lower miR-124 expression, G0/G1 phase ratio, or cell apoptosis, plus higher expression of STAT3, p-STAT3, Bcl-2 and Cyclin D1, ratio of S or G2/M phase. Transfection of miR-124 mimic and/or si-STAT3 remarkably decreased gene expression, weakened clonal formation, cell invasion, ratio of S and G2/M phase, cell apoptosis and increased G0/G1 ratio. MiR-124 up-regulation significantly suppresses STAT3, pSTAT3 and downstream Bcl-2 and Cyclin D1 expression, weakens cell invasion or malignant proliferation potency, induces G0/G1 phase arrest, and facilitates cell apoptosis. | Authentic |
Text : In modern research, mitochondria are considered a more crucial energy plant in cells. Mitochondrial dysfunction, including mitochondrial DNA (mtDNA) mutation and denatured protein accumulation, is a common feature of tumors. The dysfunctional mitochondria reprogram molecular metabolism and allow tumor cells to proliferate in the hostile microenvironment. One of the crucial signaling pathways of the mitochondrial dysfunction activation in the tumor cells is the retrograde signaling of mitochondria-nucleus interaction, mitochondrial unfolded protein response (UPRmt), which is initiated by accumulation of denatured protein and excess ROS production. In the process of UPRmt, various components are activitated to enhance the mitochondria-nucleus retrograde signaling to promote carcinoma progression, including hypoxia-inducible factor (HIF), activating transcription factor ATF-4, ATF-5, CHOP, AKT, AMPK. The retrograde signaling molecules of overexpression ATF-5, SIRT3, CREB, SOD1, SOD2, early growth response protein 1 (EGR1), ATF2, CCAAT/enhancer-binding protein-d, and CHOP also involved in the process. Targeted blockage of the UPRmt pathway could obviously inhibit tumor proliferation and metastasis. This review indicates the UPRmt pathways and its crucial role in targeted therapy of metastasis tumors. | Authentic |
Text : The aim of this study was to explore the natural course of peritoneal carcinomatosis (PC) in patients who are not fit to undergo cytoreductive (CRS) surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Over an 8-year period (2006-2013) 320 patients were excluded from CRS and HIPEC at our center. Exclusion criteria were: (a) age >75 years; (b) ASA score ≥ 3; (c) extraperitoneal disease; (d) massive disease involvement of the small bowel; (e) disease involvement of the hepatic pedicle or the pancreas; (f) invasion of retroperitoneal space; (g) more than two stenoses of the small bowel. Another 130 patients underwent CRS and HIPEC. In the HIPEC group (N=130), the mean overall survival was 26.2±11.7 months, while from the non- HIPEC group (N=320), 200 patients underwent palliative surgery, with a mean overall survival of 11.7±8.3 months. Only 120 patients received palliative chemotherapy with a mean overall survival of 7.2±4.3 months. Our study suggests that, in patients unfit to undergo CRS & HIPEC, an exploratory laparotomy and palliative surgery should be performed, offering a survival benefit and improved quality of life. | Authentic |
Text : To access antitumor effects of a combined Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and interleukin-18 (IL-18), cDNA fusion of murine GM-CSF and mature IL-18 (GMIL-18) was constructed and transfected in mammalian cells. GMIL-18 fusion protein was highly secreted and displayed bifunctional activities, possessing immune response initiation and cytokine roles, including IFN-γ induction in mouse splenocytes and increased proliferation of GM-CSF-dependent cells, M-NSF-60. The GMIL-18 secreting tumor vaccine was generated and it strongly stimulated differentiation of dendrite cells (DCs) and effusive CD8+ and CD4+ cell infiltration into tumor mice. Moreover, growth of CT26 mouse colon cancer cells was significantly retarded by GMIL-18 (CT26GMIL-18), but not by CT26GM-CSF- or CT26IL-18. The efficiency of prophylactic vaccination was greater than that of therapeutic vaccination in terms of tumor size and its inhibitory role in proliferation. In micrometastasis analysis of tumor models, γ-ray irradiated GMIL-18 tumor vaccine showed a smaller number of liver-meta tumor nodules in mouse liver cells. We concluded that bifunctional GMIL-18 fusion protein could be applied as an immune therapy for cancer treatments. | Authentic |
Text : Oncogenic RAS is a critical driver for the initiation and progression of several types of cancers. However, effective therapeutic strategies by targeting RAS, in particular RASG12D and RASG12V, and associated downstream pathways have been so far unsuccessful. Treatment of oncogenic RAS-ravaged cancer patients remains a currently unmet clinical need. Consistent with a major role in cancer metabolism, oncogenic RAS activation elevates both reactive oxygen species (ROS)-generating NADPH oxidase (NOX) activity and ROS-scavenging glutathione biosynthesis. At a certain threshold, the heightened oxidative stress and antioxidant capability achieve a higher level of redox balance, on which cancer cells depend to gain a selective advantage on survival and proliferation. However, this prominent metabolic feature may irrevocably render cancer cells vulnerable to concurrent inhibition of both NOX activity and glutathione biosynthesis, which may be exploited as a novel therapeutic strategy. In this report, we test this hypothesis by treating the HRASG12V-transformed ovarian epithelial cells, mutant KRAS-harboring pancreatic and colon cancer cells of mouse and human origins, as well as cancer xenografts, with diphenyleneiodonium (DPI) and buthionine sulfoximine (BSO) combination, which inhibit NOX activity and glutathione biosynthesis, respectively. Our results demonstrate that concomitant targeting of NOX and glutathione biosynthesis induces a highly potent lethality to cancer cells harboring oncogenic RAS. Therefore, our studies provide a novel strategy against RAS-bearing cancers that warrants further mechanistic and translational investigation. | Authentic |
Text : Non-small cell lung cancer (NSCLC) is one of the most fatal types of cancer with significant mortality and morbidity worldwide. MicroRNAs (miRs) have been confirmed to have positive functions in NSCLC. In the present study, we try to explore the role of miR-758 in proliferation, migration, invasion, and apoptosis of NSCLC cells by regulating high-mobility group box (HMGB) 3 (HMGB3.) NSCLC and adjacent tissues were collected. Reverse transcription quantitative PCR (RT-qPCR) was employed to detect expression of miR-758 and HMGB3 in NSCLC and adjacent tissues, in BEAS-2B cells and NSCLC cell lines. The targetted relationship between miR-758 and HMGB3 was identified by dual luciferase reporter gene assay. The effects of miR-758 on proliferation, migration, invasion, cell cycle, and apoptosis of A549 cells. MiR-758 expression was lower in NSCLC tissues, which was opposite to HMGB3 expression. The results also demonstrated that miR-758 can target HMGB3. The cells transfected with miR-758 mimic had decreased HMGB3 expression, proliferation, migration, and invasion, with more arrested cells in G1 phase and increased apoptosis. Our results supported that the overexpression of miR-758 inhibits proliferation, migration, and invasion, and promotes apoptosis of NSCLC cells by negative regulating HMGB2. The present study may provide a novel target for NSCLC treatment. | Authentic |
Text : The observed increase in cancer led to a continuous rise in anticancer drug preparations in Hospital Centres. The quality and security of these preparations are essential to ensure the efficacy and to limit the risk of iatrogenic toxicity. Several methods have been described to secure the process of preparation (i.e. non-analytical methods for the control during the fabrication; analytical methods for the final product evaluation). These different methods have been presented in many studies, in particular in descriptive studies, but in practice, selecting a method is difficult and related to needs and hospital priorities. Therefore, we decided to conduct this present review focused on various existing methods allowing enhancement in security of anti-cancer drugs preparation process. A proactive hazard analysis method was applied, considering preparation and control steps, to discuss the choice of a method in terms of quality and security and to identify potential risks of failure. The results show that none method is perfect. Methods with the lowest criticality score are the robotization closely followed by Drugcam® in the case of re-labelling of all containers. According to these elements a University Hospital Centre could consider these risk indexesimplementing control methods. | Authentic |
Text : Long-chain non-coding RNAs (lncRNAs) are RNA molecules with a length greater than 200 nt and no function of encoding proteins. lncRNAs play a precise regulatory function at different levels of transcription and post-transcription, and they interact with various regulatory factors to regulate gene expression, and then participate in cell growth, differentiation, apoptosis, and other life processes. In recent years, studies have shown that the abnormal expression of lncRNAs is closely related to the occurrence and development of tumors, which is expected to become an effective biomarker in tumor diagnosis. The sequencing analysis of mutations in the whole tumor genome suggests that mutations in non-coding regions may play an important role in the occurrence and development of tumors. Therefore, in-depth study of lncRNAs is helpful to clarify the molecular mechanism of tumor occurrence and development and to provide new targets for tumor diagnosis and treatment. This review introduces the molecular mechanism and clinical application prospect of lncRNAs affecting tumor development from the perspective of gene expression and regulation. | Authentic |
Text : Mesenchymal stem cells (MSCs) are pluripotent mesenchymal cells present in various adult tissues. MSCs secrete exosomes as regulators of the tumor niche, with involvement in tumorigenesis and metastasis. The regulatory role of microRNAs (miRs or miRNAs) in MSCs via targeting cyclin E1 (CCNE1) or cyclin E2 (CCNE2) has been extensively reported. Since exosomes are considered as protective and enriched sources of shuttle miRNAs, we hypothesized that exosomal transfer of miR-144 from bone marrow-derived MSCs (BMMSCs) would affect the development of non-small cell lung cancer (NSCLC) cells by targeting CCNE1 and CCNE2. We first quantified the levels of miR-144, CCNE1, and CCNE2 in NSCLC tissues and cell lines and then undertook gain- and loss-of-function studies of miR-144, CCNE1, and CCNE2 to investigate their roles in the biological characteristics of NSCLC in vitro. NSCLC cells (A549) were exposed to exosomes derived from MSCs, and cell proliferation and colony formation rate were determined using in vitro assays. Finally, effects of BMMSC-derived exosomal miR-144 on tumor development were studied in vivo. In NSCLC tissues and cell lines, miR-144 was expressed poorly and CCNE1 and CCNE2 were expressed highly. Artificially elevating miR-144 inhibited cell proliferation, colony formation, and the number of S phase-arrested cells in NSCLC by downregulating CCNE1 and CCNE2. Additionally, BMMSC-derived exosomal miR-144 led to restrained NSCLC cell proliferation and colony formation. These inhibitory effects of BMMSC-derived exosomes carrying miR-144 on NSCLC were confirmed by experiments in vivo. Collectively, these findings revealed inhibitory effects of BMMSC-derived exosomal miR-144 on NSCLC progression, which were mediated by downregulation of CCNE1 and CCNE2. | Authentic |
Text : Long noncoding RNAs (lncRNAs) play an indispensable role in cancer progression. We aim at exploring the effect of AC009022.1 on colorectal cancer (CRC) development in this paper. CRC tissues and matched normal tissues of 68 CRC patients were collected. HCT-116 and SW620 cells were transfected and grouped. The cell counting kit-8 assay, cell scratch test, and Transwell experiment were performed to sequentially detect cells proliferation, migration, and invasion. In vivo experiments were conducted. The Luciferase reporter gene assay was used. Gene expression was detected by quantitative reverse transcription polymerase chain reaction and Western blot analysis. AC009022.1 expression was abnormally elevated in CRC tissues and cells. High AC009022.1 expression in CRC patients was significantly associated with poor prognosis. Compared with the siNC group, HCT-116 and SW620 cells of siAC009022.1 group exhibited much lower OD450 value (P < .001) and invasive cell number (P < .01), and significantly higher relative wound width (P < .01). Much lower subcutaneous tumor volume and weight were found in the siAC009022.1 group compared with siNC group (P < .001). In CRC cells, AC009022.1 directly inhibited miR-497-5p expression while miR-497-5p directly hindered ACTR3B expression. Compared with HCT-116 and SW620 cells of oe-AC009022.1 group, those of oe-AC009022.1 + miR-497-5p-mimics group and oe-AC009022.1 + siACTR3B group had obviously lower OD450 value (P < .001) and invasion cell number (P < .01), and markedly higher relative wound width (P < .01). AC009022.1 enhanced CRC cell proliferation, migration, and invasion by promoting ACTR3B expression via suppressing miR-497-5p. | Authentic |
Text : This study mainly analyzes the efficacy of 0.01% atropine eye drops (low-dose atropine (LDA)) combined with virtual reality (VR)-based binocular visual function (BVF) balance training in the prevention and control of juvenile myopia. One hundred and thirty-six juvenile myopia patients admitted between November 2018 to November 2021 were selected, including 76 cases (research group) receiving LDA + VR-based BVF balance training and 60 cases (control group) treated by LDA intervention alone. Visual acuity (VA; naked vision), ocular parameters (pupil diameter (PD), axial length (AXL), and diopter), intraocular pressure (IOP), accommodation facility, clinical efficacy, and incidence of adverse reactions were observed, compared, and analyzed in both groups. After analysis, it was found that the research group showed significantly higher naked vision and PD while statistically lower D after intervention than the corresponding preinterventional parameters than the control group. While AXL showed no statistical difference between the groups and within groups. The IOP also differed insignificantly between groups, but the post-treatment accommodation facility was better in the research group compared with the baseline (before treatment) and control group. In terms of curative effects, an obviously higher total effective rate was determined in the research group. In addition, the two groups showed no significant difference in the incidence of adverse reactions. LDA + VR-based BVF balance training deserves clinical popularization, as it can prevent and control myopia among teenagers, with better adjusting effects on eye function and certain safety. | Counterfeit |
Text : Liver cancer is one of the most common malignancies in the world and a leading cause of cancer-related mortality. Accumulating evidence has highlighted the critical role of long noncoding RNAs (lncRNAs) in various cancers. The present study aimed to explore the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in cell growth and migration in MHCC97 cells and its underlying mechanism. First, we assessed the expression of UCA1 in MHCC97 and three other cell lines by RT-qPCR. Then the expression of UCA1, miR-301a, and CXCR4 in MHCC97 cells was altered by transient transfection. The effects of UCA1 and miR-301 on cell viability, migration, invasion, and apoptosis were assessed. The results revealed that UCA1 expression was relatively higher in MHCC97 cells than in MG63, hFOB1.19, and OS-732 cells. Knockdown of UCA1 reduced cell viability, inhibited migration and invasion, and promoted cell apoptosis. However, the effect of UCA1 knockdown on cell growth and migration was blocked by miR-301a overexpression, whose expression was regulated by UCA1. We also found that miR-301a positively regulated CXCR4 expression. CXCR4 inhibition reversed the effect of miR-301a overexpression on cell growth and migration. Moreover, miR-301a activated the Wnt/β-catenin and NF-κB pathways via regulating CXCR4. The present study demonstrated that UCA1 inhibition exerted an antigrowth and antimigration role in MHCC97 cells through regulating miR-301a and CXCR4 expression. | Counterfeit |
Text : Chemotherapy is the most common method to treat leukemia as well as other types of human cancers. However, drug resistance has remained as the main challenge against the efficacy of treatments. Furthermore, having various adverse effects, chemotherapy drugs are becoming replaced by natural modalities for cancer therapy. In this regard, herbal components such as resveratrol and prednisolone have been identified to sensitize the leukemic cells to programmed cell death through a set of complex processes. In this study, we have examined DNA methylation on the human multidrug resistance gene 1 (MDR1) as a well-known marker for cellular drug resistance. We evaluated the effect of resveratrol and prednisolone on DNA methylation patterns of MDR1 gene promoter in the CCRF-CEM cell line as a representative for acute lymphoblastic leukemia. The study was aimed to clarify whether the MDR1 gene expression is regulated via DNA promoter methylation as a potential underlying mechanism, following exposure to resveratrol and prednisolone. Our data revealed that despite a strong influence to down-regulate the MDR1 expression, Resveratrol and Prednisolone did not alter the methylation pattern, suggesting other regulatory mechanisms in controlling the MDR1 expression in CCRF-CEM cell line. Unchanged status of DNA methylation of MDR1 gene may suggest that Resveratrol and Prednisolone causes the gene expression changes through a distinct mechanism which requires further studies to be understood. A more detailed understanding of the mechanisms beyond the regulation of the genes involved in cancer formation will help to design novel therapeutic strategies to fight the human cancers. | Authentic |
Text : Laryngeal cancers are mostly squamous cell carcinomas. Although targeting radio-resistant cancer cells is important for improving the treatmental efficiency, the signaling pathway- and therapeutic strategy-related to laryngeal carcinoma still require further study. Galangin is an active pharmacological ingredient, isolated from propolis and Alpinia officinarum Hance, and has been reported to have anticancer and anti-oxidative properties through regulation of cell cycle, resulting in angiogenesis, apoptosis, invasion and migration without triggering any toxicity in normal cells. PI3K/AKT and p38 are important signaling pathways to modulate cancer cell apoptosis and proliferation through caspase-3, NF-κB and mTOR signal pathways. Autophagy is also enhanced by activating LC3s and Beclin 1. In the present study, galangin was found to suppress laryngeal cancer cell proliferation. Also, flow cytometry, immunohistochemical and western blot analysis indicated that cell apoptosis was induced for galangin administration, promoting caspase-3 expression through regulating PI3K/AKT/NF-κB. Furthermore, galangin inhibited laryngeal cancer cell proliferation, related to p38 inactivation by galangin treatment. Additionally, mTOR activation regulated by PI3K/AKT was reduced by galangin, suppressing cancer cell transcription and proliferation. Our data also indicated that the tumor volume and weight in nude mice were reduced for galangin use in vivo accompanied by Ki-67 decrease and TUNEL increase in tumor tissues. Together, our data indicated that galangin has a potential role in suppressing human laryngeal cancer via inhibiting tumor cell proliferation, activating apoptosis and autophagy, which were regulated by p38 and AKT/NF-κB/mTOR pathways, providing a therapeutic strategy for human laryngeal cancer treatment. | Authentic |
Text : microRNAs (miRNAs) have been revealed to participate in some oral cancers and are proved to be effective. In the present study, we tried to explore the biological function of miR-133a in oral squamous cell carcinoma (OSCC) cells. The relationship that C-terminal-binding proteins 2 (CTBP2) was the putative target gene of miR-133a revealed from bioinformatics analysis was further was further validated by dual-luciferase reporter gene assay. In total, 40 patients with OSCC were enrolled for characterization of miR-133a, CTBP2, and Notch signaling pathway-related gene expression in clinical OSCC tissues. Low expression of miR-133a and high expression of CTBP2, Hes1, Notch-1, and Notch-3 were determined in OSCC tissues. OSCC cell lines were transfected with miR-133a inhibitor, miR-133a mimic, or shRNA targeting CTBP2, in response to which cell proliferation, migration, invasion, cell cycle, and apoptosis were evaluated. Transfection of miR-133a mimic induced apoptosis and inhibited OSCC cell proliferation, migration, and invasion and this was demonstrated to be attributable to decreased CTBP2 expression and suppression of the Notch signaling pathway. Taken together, we concluded that miR-133a acted as a tumor suppressor in OSCC through inhibition of the Notch signaling pathway via binding to CTBP2. | Counterfeit |
Text : This study aims to investigate the role of circular antisense non-coding RNA at the INK4 locus (cANRIL) in the inflammatory response of vascular endothelial cells (ECs) in a rat model of coronary atherosclerosis (AS). A rat model of AS was established with rats that were injected with a large dose of vitamin D3 and fed a high-fat diet. Sixty Wistar rats were randomly assigned into control, model, empty vector, over-expressed cANRIL and low-expressed cANRIL groups (12 rats in each group). Sixteen weeks later, the ultrastructure of their coronary arteries was observed via transmission electron microscopy. Rat serum lipid levels were analyzed using an automatic biochemical analyzer, and their atherogenic index (AI) values were calculated. Hematoxylin and eosin staining was used to observe the endothelial morphology of rats. Additionally, rat EC apoptosis was tested via a TUNEL assay. Enzyme-linked immunosorbent assays (ELISAs) were applied to measure serum levels of interleukin-1 (IL-1), IL-6, matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP). The cANRIL, Bax, bcl-2 and caspase-3 mRNA expression levels were measured with a quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Bax, bcl-2 and caspase-3 were detected using immunohistochemistry. In the control group, ECs were closely arranged with normal structures, and there was no proliferation. In the model, empty vector and over-expressed cANRIL groups, some cells were not present, and atherosclerotic plaques and thrombi appeared. However, in the under-expressed cANRIL group, the cells had a normal structure. Compared with the model and empty vector groups, the levels of total cholesterol (CHOL), triglycerides (TGs), low density lipoprotein (LDL), IL-1, IL-6, MMP-9, CRP, cANRIL, Bax, and caspase-3, AI values, and rates of EC apoptosis decreased in the low-expressed cANRIL group, while HDL (high density lipoprotein) levels and mRNA and protein expression levels of bcl-2 were increased. The changes in expression levels in the over-expressed cANRIL group were the opposite of those in the low-expressed cANRIL group. Our study provides evidence that reduced cANRIL expression could prevent coronary AS by reducing vascular EC apoptosis and inflammatory factor expression. | Counterfeit |
Text : With changes in lifestyle and an increase in bad health habits, cancer has become a noncommunicable and frequently occurring disease that poses a serious threat to human life. Cancer is associated with high rates of morbidity and mortality worldwide. As a major negative life event, advanced malignancies lead to strong mood swings in most patients. Furthermore, various internal and external factors can have a huge impact on patients' physical and mental health and put them in a stressful situation, causing a series of psychological stress responses. To explore the degree of fear of disease progression in patients with advanced cancer and the usefulness of dignity therapy. Overall, 120 patients with advanced malignant tumors admitted to Shijiazhuang No. 1 hospital between January 2019 and January 2020 were enrolled. The selected patients were divided into the test and control groups (60 people per group) using a random number table. All patients received basic treatment. Patients in the trial group also received dignity therapy. The intervention period was 4 weeks. Simplified scales were used for assessing disease progression (FoP-Q-SF) and quality of life (QLQ-C30) before and after the intervention, and the scores were compared between the groups. After the intervention, the degree of fear in the experimental group was lower than that of the control group. Cognitive function, emotional function, and the scores of the overall health status of the experimental group were higher than those of the control group. Additionally, the scores of fatigue, insomnia, loss of appetite, and diarrhea in the experimental group were lower than those of the control group (P < 0.05). The social support level scale scores, depression scores, hospital anxiety and depression scale scores, and patient dignity inventory scores of the experimental group were lower than those of the control group (P < 0.05). Patients with advanced malignant tumors have fear, anxiety, and depression related to disease progression. Dignity therapy is useful for improving the patients' quality of life, increasing dignity, and enhancing social support. | Authentic |
Text : In recent years, microRNAs (miRNAs/miRs) have been shown to be deregulated in epithelial ovarian cancer (EOC). Their deregulation has been suggested to be involved in EOC formation and progression through the regulation of the expression of numerous cancer‑related genes. Hence, it is of great importance to further determine the detailed roles and underlying mechanisms of miRNAs involved in EOC and to identify novel targets for diagnosis, prognosis and treatment of patients with EOC. In this study, the expression of miR‑655‑3p (miR‑655) was significantly downregulated in EOC tissues and four EOC cell lines. After miR‑655 was restored, functional assays revealed that cellular proliferation and invasion were considerably reduced in EOC. Additionally, vascular endothelial growth factor (VEGF) A was identified as a direct target gene of miR‑655 in EOC cells. Furthermore, VEGF knockdown could mimic the tumour‑suppressive roles of miR‑655 overexpression in EOC cells. Moreover, the introduction of VEGF abrogated the effects of miR‑655‑induced proliferation and invasion inhibition in EOC cells. Altogether, these findings indicated that miR‑655 may inhibit EOC cell proliferation and invasion by repressing VEGF. Thus, the miR‑655/VEGF pathway could serve as a novel therapeutic target for patients with EOC. | Counterfeit |
Text : The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed in vivo and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer. | Authentic |
Text : The morbidity and mortality rates of nonsmall-cell lung cancer (NSCLC) have increased in recent years. We aimed to explore the biological role of fibroblast growth factor 5 (FGF5) in NSCLC. We first established that the expression of FGF5 was increased in NSCLC tissues compared with the normal adjacent tissues. The expression of FGF5 was also increased in NSCLC cell lines. The effect of FGF5 silencing on cell proliferation, cell cycle, apoptosis, migration, and invasion of H661 and CALU1 cells was then examined. Downregulation of FGF5 significantly inhibited cell proliferation and induced G1 phase cell cycle arrest compared with the negative control small interfering (siNC) groups. Cell apoptosis was promoted by siFGF5 treatment. Cell migration and invasion of H661 and CALU1 cells with siFGF5 transfection were markedly diminished compared with the siNC groups. In addition, migration and invasion-associated proteins (E-cadherin, matrix metalloproteinase-2 [MMP-2], and MMP-9) and epithelial mesenchymal transition markers (N-cadherin, vimentin, snail, and slug) were also regulated by FGF5 siRNA treatment. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) cell cycle and vascular endothelial growth factor (VEGF) pathways were correlated with FGF5 expression, which was further confirmed in NSCLC cells by Western blot analysis. Our results indicated that FGF5 silencing suppressed cell growth and invasion via regulation of the cell cycle and VEGF pathways. Therefore, FGF5 may serve as a promising therapeutic strategy for NSCLC. | Authentic |
Text : Plasmablastic lymphoma (PBL) is a B-cell malignancy associated with human immunodeficiency virus (HIV). PBL could also influence the HIV-negative patients. The study aimed to identify prognostic factors for survival among Chinese PBL patients. Eligible patients from literature and Peking Union Medical College Hospital (PUMCH) were included in this study. Clinical characteristics and immunophenotypic data were extracted. Kaplan-Meier curve was used to describe the survival status. Cox regression was used for multivariate analysis. A total of 60 Chinese PBL patients were included, including 54 patients from 36 published articles and 6 new patients that have not been reported. The median overall survival was 7 months (95% confidence interval 3.853-10.147 months). An overwhelming majority (79.31%) of the included cases were Ann Arbor stage IV patients. All the Chinese PBL patients were HIV-negative; 46.81% were Epstein-Barr virus-positive. CD38, CD138, or MUM1 was positively expressed in more than 80% of patients; CD20 expression was also found in 22.03% of cases. Kaplan-Meier curve revealed obvious differences in patient survival between patients in primary stages and advanced stages, as well as between patients with kidney involvement and those without kidney involvement. Cox regression analysis indicated that stage and age were 2 prognostic factors for patient survival. Advanced stage might be associated with poor prognosis among PBL HIV-negative patients in Chinese. | Authentic |
Text : Gastric cancer is the third leading cause of cancer mortality all over the world. The combination therapy of surgery with chemotherapy, that is, 5-fluorouracil (5-FU) and platinum-containing anticancer drugs, is becoming a current clinical strategy for patients with gastric cancer because of the lower curative rate and higher cancer recurrence rate of patients treated with only surgery. However, the development of drug resistance in cancer cells is still the most challenge in clinical chemotherapy. Excision repair cross-complementing 1 (ERCC1), an essential member of nucleotide excision repair system, recently has been suggested to be a predictive biomarker of treatment evaluation and might affect the outcomes of chemotherapy. Thus, this study was aimed to investigate whether ERCC1 expression could be regulated, and its role in gastric cancer cells treated with 5-FU and the underlying mechanism. Human AGS gastric cancer cells were used in this study. It was shown that ERCC1 expression could be upregulated in AGS cells treated with 5-FU and this upregulation could subsequently attenuate the cytotoxicity of 5-FU in AGS cells. Moreover, 5-FU-upregulated ERCC1 expression was regulated by extracellular signal-regulated kinase (ERK) 1/2 and p38 signaling through activating the transcription factor c-jun/activator protein (AP)-1. These results indicated the role of ERCC1 in the development of drug resistance to 5-FU in AGS cells. The mechanism elucidation concerning the ERK1/2 and p38 kinases and transcription factor c-jun/AP-1 might contribute another idea to the development of chemotherapy strategy for the gastric cancers in the future. | Authentic |
Text : Mdm2 antagonizes the tumor suppressor p53. Targeting the Mdm2-p53 interaction represents an attractive approach for the treatment of cancers with functional p53. Investigating mechanisms underlying Mdm2-p53 regulation is therefore important. The scaffold protein β-arrestin2 (β-arr2) regulates tumor suppressor p53 by counteracting Mdm2. β-arr2 nucleocytoplasmic shuttling displaces Mdm2 from the nucleus to the cytoplasm resulting in enhanced p53 signaling. β-arr2 is constitutively exported from the nucleus, via a nuclear export signal, but mechanisms regulating its nuclear entry are not completely elucidated. β-arr2 can be SUMOylated, but no information is available on how SUMO may regulate β-arr2 nucleocytoplasmic shuttling. While we found β-arr2 SUMOylation to be dispensable for nuclear import, we identified a non-covalent interaction between SUMO and β-arr2, via a SUMO interaction motif (SIM), that is required for β-arr2 cytonuclear trafficking. This SIM promotes association of β-arr2 with the multimolecular RanBP2/RanGAP1-SUMO nucleocytoplasmic transport hub that resides on the cytoplasmic filaments of the nuclear pore complex. Depletion of RanBP2/RanGAP1-SUMO levels result in defective β-arr2 nuclear entry. Mutation of the SIM inhibits β-arr2 nuclear import, its ability to delocalize Mdm2 from the nucleus to the cytoplasm and enhanced p53 signaling in lung and breast tumor cell lines. Thus, a β-arr2 SIM nuclear entry checkpoint, coupled with active β-arr2 nuclear export, regulates its cytonuclear trafficking function to control the Mdm2-p53 signaling axis. | Authentic |
Text : The objective of the study was to elucidate the mechanism by which microRNA-34a (miR-34a) influences heart development and participates in the pathogenesis of congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling pathway. Forty D7 pregnant mice were recruited for the purposes of the study and served as the CHD (n=20, successfully established as CHD model) and normal (n=20) groups. The positive expression of the NOTCH-1 protein was evaluated by means of immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups. The expressions of miR-34a, NOTCH-1, Jagged1, Hes1, Hey2 and Csx in cardiac tissues and ECCs were determined by both RT-qPCR and western blotting methods. MTT assay and flow cytometry were conducted for cell proliferation and apoptosis measurement. A dual luciferase reporter assay was applied to demonstrate that NOTCH-1 was the target gene of miR-34a. In comparison to the normal group, the expressions of miR-34a, Jagged1, Hes1 and Hey2 displayed up-regulated levels, while the expressions of NOTCH-1 and Csx were down-regulated in the CHD group. Compared with the blank and NC groups, the miR-34a mimics and siRNA-NOTCH-1 groups displayed reduced expressions of NOTCH-1 and Csx as well as a decreased proliferation rate, higher miR-34a, Jagged1, Hes1 and Hey2 expressions and an increased rate of apoptosis; while an reverse trend was observed in the miR-34a inhibitors group. The expressions of MiR-34a recorded increased levels in the miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups, however no changes in the expressions of NOTCH-1, Jagged1, Hes1, Hey2, Csx, as well as cell proliferation and apoptosis were observed when compared to the blank and NC groups. The results of our study demonstrated that miR-34a increases the risk of CHD through its downregulation of NOTCH-1 by modulating the Notch signaling pathway. | Counterfeit |
Text : Exosomes from cancer cells or immune cells, carrying bio-macromolecules or microRNAs (miRNAs), participate in tumor pathogenesis and progression by modulating microenvironment. Our study aims to investigate the role of these microRNA-501-3p (miR-501-3p) containing exosomes derived from tumor-associated macrophage (TAM) in the progression of pancreatic ductal adenocarcinoma (PDAC). Firstly, the function of TAM recruitment in PDAC tissues was assessed, followed by identification of the effects of M2 macrophage-derived exosomes on PDAC cell activities and tumor formation and metastasis in mice. In silico analysis was conducted to predict differentially expressed genes and regulatory miRNAs related to PDAC treated with macrophages, which determined miR-501-3p and TGFBR3 for subsequent experiments. Next, gain- and loss-of-function experiments were performed to examine their role in PDAC progression with the involvement of the TGF-β signaling pathway. TAM recruitment in PDAC tissues was associated with metastasis. Highly expressed miR-501-3p was observed in PDAC tissues and TAM-derived exosomes. Both M2 macrophage-derived exosomes and miR-501-3p promoted PDAC cell migration and invasion, as well as tumor formation and metastasis in nude mice. MiR-501-3p was verified to target TGFBR3. PDAC cells presented with down-regulated TGFBR3, which was further decreased in response to M2 macrophage treatment. TGF-β signaling pathway activation was implicated in the promotion of miR-501-3p in PDAC development. The suppression of macrophage-derived exosomal miR-501-3p resulted in the inhibition of tumor formation and metastasis in vivo. M2 macrophage-derived exosomal miR-501-3p inhibits tumor suppressor TGFBR3 gene and facilitates the development of PDAC by activating the TGF-β signaling pathway, which provides novel targets for the molecular treatment of PDAC. | Counterfeit |
Text : Combination treatment through simultaneous delivery of anticancer drugs and gene with nano-formulation has been demonstrated to be an elegant and efficient approach for colorectal cancer therapy. Recently, sorafenib being studied in combination therapy in colorectal cancer (CRC) attracted attention of researchers. On the basis of our previous study, pigment epithelium-derived factor (PEDF) loaded nanoparticles showed good effect on CRC in vitro and in vivo. Herein, we designed a combination therapy for sorafenib (Sora), a multi-kinase inhibitor and PEDF, a powerful antiangiogenic gene, in a nano-formulation aimed to increase anti-tumor effect on CRC for the first time. Sora and PEDF were simultaneously encapsulated in PEG-PLGA based nanoparticles by a modified double-emulsion solvent evaporation method. The obtained co-encapsulated nanoparticles (Sora@PEDF-NPs) showed high entrapment efficiency of both Sora and PEDF - and exhibited a uniform spherical morphology. The release profiles of Sora and PEDF were in a sustained manner. The most effective tumor growth inhibition in the C26 cells and C26-bearing mice was observed in the Sora@PEDF-NPs in comparison with none-drug nanoparticles, free Sora, mono-drug nanoparticles (Sora-NPs and PEDF-NPs) and the mixture of Sora-NPs and equivalent PEDF-NPs (Mix-NPs). More importantly, Sora@PEDF-NPs showed lower toxicity than free Sora in mice according to the acute toxicity test. The serologic biochemical analysis and mice body weight during therapeutic period revealed that Sora@PEDF-NPs had no obvious toxicity. All the data demonstrated that the simultaneously loaded nanoparticles with multi-kinase inhibitor and anti-angiogenic gene might be one of the most potential formulations in the treatment of colorectal carcinoma in clinic and worthy of further investigation. | Authentic |
Text : This study aims to investigate the role of lncRNA growth arrest-specific transcript 5 (GAS5)/miR-362-5p/suppressor of morphogenesis in the genitalia 1 (SMG1) axis in 131 I-resistance in thyroid cancer (TC). GAS5, miR-362-5p, and SMG1 expression in TC tissues was assessed and the 131 I-resistant TC cells were established, which were treated with altered GAS5, miR-362-5p, and SMG1. The proliferation and apoptosis of 131 I-resistant TC cells were detected, and the expression of Akt/mTOR signaling pathway-related proteins was assessed. Binding relations between GAS5 and miR-362-5p, and miR-362-5p and SMG1 were confirmed. The role of GAS5 in 131 I-resistant TC cell growth in vivo was observed. GAS5 was downregulated and miR-362-5p was upregulated in TC tissues and 131 I-resistant cells. The 131 I-resistant TC cells had enhanced proliferation and repressed apoptosis, and the Akt/mTOR signaling pathway was activated. Overexpressed GAS5 strengthened 131 I sensitivity and suppressed TC cell growth, while upregulated miR-362-5p had an opposite effect. MiR-362-5p upregulation reversed the effect of GAS5, and SMG1 overexpression eliminated the impact of miR-362-5p upregulation on 131 I-resistant TC cells. GAS5 competitively binds to miR-362-5p and SMG1 is targeted by miR-362-5p. GAS5 sponges miR-362-5p to promote sensitivity of TC cells to 131 I by upregulating SMG1 and inactivating Akt/mTOR signaling pathway. | Counterfeit |
Text : Over 90% of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. This study investigated the antitumor efficacy of the inhibition of cell division cycle protein 20 (CDC20) and heparanase (HPSE) expression in Hepa1-6 mouse hepatoma cells. Cell viability was measured by the MTT assay. Cell cycle was analyzed by cytometry. The invasion assay was performed using the Transwell chamber. The orthotopic liver tumor model was established by inoculating the livers of immunocompetent Kunming mice with Hepa1-6 cells. The MTT assay showed that 50 and 100 nM CDC20 siRNA-1 and HPSE siRNA-2 significantly reduced Hepa1-6 cell viability with the combination of CDC20 and HPSE siRNA being the most effective. Silencing of CDC20 or both CDC20 and HPSE expression significantly induced G2/M phase cell cycle arrest in Hepa1-6 HCC cells. Silencing HPSE expression significantly inhibited the invasion ability of Hepa1-6 cells with the combination of CDC20 and HPSE silencing being more effective than HPSE alone. Silencing CDC20 and HPSE expression significantly inhibited HCC tumor growth in the orthotopic liver tumor model, but the combination was most effective. Silencing CDC20 and HPSE expression activated cell apoptosis and autophagy. In conclusion, targeting inhibition of both CDC20 and HPSE expression is an ideal strategy for HCC therapy. | Authentic |
Text : Although microRNA‑33 (miR‑33) family members are known to be involved in the regulation and balancing of cholesterol metabolism, fatty acid oxidation and insulin signaling, their functions in carcinogenesis are controversial and the underlying mechanisms have remained elusive. Gastric cancer is the fourth most common malignancy in the world; however, the dysregulation and function of miR‑33 family members in gastric cancer have not been extensively studied. The present study reported that a miR‑33 family member, miR‑33a, was significantly downregulated in gastric cancer tissues and gastric cancer cell lines. Of note, the expression of miR‑33a was inversely correlated with pathological differentiation and metastasis as well as gastric cancer biomarker CA199. A cell‑counting kit‑8 assay showed that transfection of the SGC‑7901 gastric cell line with miR‑33a‑overexpression plasmid inhibited the capability of the cells to proliferate. Furthermore, overexpression of miR‑33a led to cell cycle arrest of SGC‑7901 cells in G1 phase. In addition, a luciferase reporter assay showed that miR‑33a directly targeted cyclin‑dependent kinase 6 (CDK6), cyclin D1 (CCND1) and serine/threonine kinase PIM‑1. In gastric cancer specimens, the reduced expression of miR‑33a was associated with increased expression of CDK‑6, CCND1 and PIM1. However, only PIM1 expression was significantly increased in cancer tissues compared with that in their adjacent tissues. The present study revealed that miR‑33a was downregulated in gastric cancer tissues and cell lines, while forced overexpression of miR‑33a decreased CDK‑6, CCND1 and PIM1 expression to inhibit gastric cancer cell proliferation by causing G1 phase arrest. miR‑33a overexpression may therefore resemble an efficient strategy for gastric cancer therapy. | Authentic |
Text : Various circular RNAs (circRNAs) have been reported to involve in carcinoma. This study explored the role and mechanism of circRNA circFNDC3B (circFNDC3B) in renal carcinoma (RC). The detection indicators in this paper were viability, colony, and migration, which respectively investigated by Cell Counting Kit-8, colony formation, and migration assay. Reverse transcriptase quantitative polymerase chain reaction tested and cell transfection changed circFNDC3B and miR-99a expression. Moreover, western blot tested relate-proteins of proliferation, migration, and cell pathways were examined by western blot. circFNDC3B was upregulated at RC tissues. circFNDC3B enhanced cell viability, colony and migration, and miR-99a mimic played reverse impacts. Furthermore, circFNDC3B negatively regulated miR-99aand circFNDC3B restrained the janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) and extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathways by miR-99a downregulation. Overexpression of circFNDC3B enhanced cell viability, colony formation and migration by miR-99a downregulation via JAK1/STAT3 and MEK/ERK pathways. | Authentic |
Text : Primary intra-abdominal synovial sarcomas are rare soft tissue malignancies. Herein, we present a case of poorly differentiated monophasic synovial sarcomain ileum mesenterieswith pulmonary metastasis. The patient was a 47-year-old female with a history of cough with variable expectoration and paroxysmal abdominal pain for two months. The tumor was located in ileum mesenteries and composed of monophasic spindle tumor cells with active mitosis and massive necrosis. Tumor cells were positive for vimentin and BCL-2 by immunohistochemistry staining and positive for SYT gene break apart by dual color break apart fluorescence in situ hybridization assay. The differential diagnosis includes gastrointestinal stromal tumour and other mesenchymal tumour. | Authentic |
Text : Hydroxychloroquine (HCQ) is being tested in a number of human clinical trials to determine the role of autophagy in response to standard anticancer therapies. However, HCQ pharmacodynamic (PD) responses are difficult to assess in patients, and preclinical studies in mouse models are equivocal with regard to HCQ exposure and inhibition of autophagy. Here, pharmacokinetic (PK) assessment of HCQ in non-tumor-bearing mice after intraperitoneal dosing established 60 mg/kg as the human equivalent dose of HCQ in mice. Autophagy inhibition, cell proliferation, and cell death were assessed in two-dimensional (2D) cell culture and three-dimensional tumor organoids in breast cancer. Mice challenged with breast cancer xenografts were then treated with 60 mg/kg HCQ via intraperitoneal dosing, and subsequent PK and PD responses were assessed. Although autophagic flux was significantly inhibited in cells irrespective of autophagy-dependence status, autophagy-dependent tumors had decreased cell proliferation and increased cell death at earlier time points compared with autophagy-independent tumors. Overall, this study shows that 2D cell culture, three-dimensional tumor organoids, and in vivo studies produce similar results, and in vitro studies can be used as surrogates to recapitulate in vivo antitumor responses of HCQ. SIGNIFICANCE STATEMENT: Autophagy-dependent tumors but not autophagy-independent tumors have decreased cell proliferation and increased cell death after single-agent hydroxychloroquine treatment. However, hydroxychloroquine causes decreased autophagic flux regardless of autophagy status, suggesting its clinical efficacy in the context of autophagy inhibition. | Authentic |
Text : Previous studies have been indicated that tumor necrosis factor receptor-associated factor 6 (TRAF6)-induced inflammation leads to acute kidney injury (AKI). How microRNA (miR) contributes to this process is poorly defined. The aim of this study was to investigate whether miR-590-3p regulated lipopolysaccharide (LPS)-induced inflammatory response by inhibiting TRAF6. LPS-induced septic mice were treated with adenovirus expressing miR-590-3p (ad-miR-590-3p) via tail-vein injection. AKI was evaluated by examining serum cystatin C (CysC), serum β2-microglobulin (β2-MG), and blood urea nitrogen (BUN). The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. The proliferation of podocytes was monitored using the MTT assay. Cell apoptosis was analyzed by flow cytometry. Survival outcomes in ad-miR-590-3p-transfected septic mice were markedly improved compared with mice with LPS-induced sepsis. Ad-miR-590-3p transfection significantly attenuated LPS-induced AKI, which was reflected by an improved glomerular filtration rate (GFR) as determined by measuring CysC, β2-MG, and BUN. Moreover, we observed that miR-590-3p was a novel regulator of TRAF6, binding to its 3'-untranslated regions (3'-UTRs). In vitro, a miR-590-3p gain-of-function mutation blocked LPS-induced podocyte growth inhibition and apoptosis, as well as overactivation of the inflammatory response. miR-590-3p has the ability to suppress LPS-induced AKI and podocyte apoptosis by targeting TRAF6. This might provide a novel strategy for the treatment of LPS-induced renal injuries. | Authentic |
Text : A long non‑coding RNA (lncRNA) called prostate cancer‑associated non‑coding RNA 1 (PRNCR1) serves crucial roles in the aggressive phenotypes of colorectal cancer and non‑small cell lung cancer. However, there is little research on the expression profile, clinical value and detailed functions of PRNCR1 in tongue squamous cell carcinoma (TSCC). The aim of the present study was to determine PRNCR1 expression in TSCC and to examine the involvement of PRNCR1 in TSCC progression. The molecular mechanisms behind the oncogenic effects of PRNCR1 in TSCC cells were also investigated. PRNCR1 was revealed to be upregulated in TSCC tumors and cell lines. The high PRNCR1 expression showed a significant correlation with tumor size, clinical stage, lymph node metastasis, and shorter overall survival times among patients with TSCC. A PRNCR1‑knockdown reduced TSCC cell proliferation, migration and invasion, and increased apoptosis in vitro. Additionally, the PRNCR1‑knockdown slowed down in vivo tumor growth of TSCC cells. With regards to the mechanism, PRNCR1 acted as a competing endogenous RNA on microRNA‑944 (miR‑944) in TSCC cells, and the effects of the PRNCR1‑knockdown were reversed by an miR‑944‑knockdown. HOXB5 was validated as a direct target gene of miR‑944 in TSCC cells, and HOXB5 expression was found to be positively regulated by PRNCR1. Furthermore, resumption of HOXB5 expression reversed the tumor‑suppressive actions of miR‑944 in TSCC cells. In conclusion, PRNCR1 acts as an oncogenic lncRNA in TSCC through the upregulation of HOXB5 by sponging miR‑944, thereby indicating a potential therapeutic target in TSCC. | Counterfeit |
Text : Chemotherapy is one of the most common therapeutic option for metastatic tumors and hematological malignancies. ABCB1-mediated multidrug resistance is the major obstacle for chemotherapy. Natural products with diversified structures are ideal source of ABCB1 modulators. Ganoderenic acid B, a lanostane-type triterpene isolated from Ganoderma lucidum, exhibited potent reversal effect on ABCB1-mediated multidrug resistance of HepG2/ADM cells to doxorubicin, vincristine and paclitaxel. Similarly, ganoderenic acid B could also significantly reverse the resistance of ABCB1-overexpressing MCF-7/ADR cells to doxorubicin. Furthermore, ganoderenic acid B notably enhanced intracellular accumulation of rhodamine-123 in HepG2/ADM cells through inhibition of its efflux. ABCB1 siRNA interference assay indicated that the reversal activity of ganoderenic acid B was dependent on ABCB1. Further mechanistic investigations found that ganoderenic acid B did not alter the expression level of ABCB1 and the activity of ABCB1 ATPase. Molecular docking model displayed that the positions of ganoderenic acid B binding to ABCB1 were different from the region of verapamil interacted with ABCB1. Collectively, ganoderenic acid B can enhance the cytotoxicity of chemotherapeutics towards ABCB1-mediated MDR cancer cells via inhibition of the transport function of ABCB1. These findings provide evidence that ganoderenic acid B has the potential to be developed into an ABCB1-mediated multidrug resistance reversal agent. | Authentic |
Text : To explore the diagnosis of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) by cervical biopsy under colposcopy and analyze the factors influencing the detection. The clinical data of 134 CIN confirmed by colposcopy biopsy in our hospital from June 2018 to October 2019 and subsequent LEEP treatment were analyzed retrospectively. All patients were diagnosed pathologically after the operation. The diagnosis of CIN by cervical biopsy under colposcopy was observed. The influencing factors of CIN and ICC detected by colposcopy biopsy were analyzed by the pathological results of loop electrosurgical excision procedure (LEEP) as the gold standard. After LEEP, the number of the no intraepithelial or malignant lesions (NILM) or ICC were higher than that of colposcopy biopsy, and CIN-III was lower than that of colposcopy biopsy, the differences were all statistically significant (P < 0.05). Among the 134 patients, the coincidence rate between colposcopy biopsy and LEEP examination results was 79.10% (106/134), and postoperative pathological findings showed that there were 13 cases (9.70%) with the pathological upgrade and 19 cases (14.18%) with pathological decrease. Multivariate logistic analysis showed that the image quality of colposcopy image, atypical blood vessels, biopsy sampling method, and visible lesion area of the cervix were the independent influencing factors for the detection of CIN and ICC by colposcopy biopsy (P < 0.05). CIN and ICC can be diagnosed by colposcopy cervical biopsy and postoperative histopathology. However, there are still some missed and misdiagnosed cervical biopsies under colposcopy, and the combined detection of the two can further ensure the diagnosis rate. The clinical registration number is E2018091. | Authentic |
Text : In the literature, some articles report that the incidence of numerous diseases increases among the individuals who live around high-voltage electric transmission lines (HVETL) or are exposed vocationally. However, it was not investigated whether HVETL affect bone metabolism, oxidative stress, and the prevalence of thyroid nodule. Dual-energy X-ray absorptiometry (DEXA) bone density measurements, serum free triiodothyronine (FT3), free thyroxine (FT4), RANK, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), phosphor, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were analyzed to investigate this effect. Bone mineral density levels of L1-L4 vertebrae and femur were observed significantly lower in the electrical workers. ALP, phosphor, RANK, RANKL, TOS, OSI, and anteroposterior diameter of the left thyroid lobe levels were significantly higher, and OPG, TAS, and FT4 levels were detected significantly lower in the study group when compared with the control group. Consequently, it was observed that the balance between construction and destruction in the bone metabolism of the electrical workers who were employed in HVETL replaced toward destruction and led to a decrease in OPG levels and an increase in RANK and RANKL levels. In line with the previous studies, long-term exposure to an electromagnetic field causes disorders in many organs and systems. Thus, it is considered that long-term exposure to an electromagnetic field affects bone and thyroid metabolism and also increases OSI by increasing the TOS and decreasing the antioxidant status. | Authentic |
Text : ATP citrate lyase (ACLY) is a key enzyme of lipogenesis in cells. However, ACLY expression in renal cell carcinoma (RCC) and its association with clinicopathological parameters remain unclear. The present study aimed to evaluate ACLY expression levels in RCC and adjacent normal tissues. This study included 33 patients with clear cell RCC (ccRCC). ACLY protein was assayed using immunohistochemistry and western blotting methods. ACLY mRNA expression was determined by reverse transcription-quantitative polymerase chain reaction. Serum ACLY concentrations were measured using the ELISA. Compared with adjacent normal tissues, significantly higher levels of ACLY protein expression were observed in all of the ccRCC tissues (P<0.05). ACLY protein levels were positively associated with the T stage and nuclear grade of RCC. ACLY immunostaining was located in the cytoplasm and nucleus. ACLY protein levels and ACC1 mRNA expression in RCC tissues were significantly higher compared with that in adjacent normal tissues (P<0.05). There were no significant differences in serum ACLY concentrations between patients with RCC and health controls (P>0.05). Preliminary evaluation of ACLY function showed that ACLY small interfering RNA downregulation inhibited RCC cell proliferation and migration, but promoted RCC cell apoptosis. ACLY may be a novel biomarker for the evaluation of biological aggressiveness and may be a potential target for RCC treatment. | Authentic |
Text : This study aims to determine the effects of artesunate on proliferation, apoptosis and β-catenin expression in the human osteosarcoma cell line MG-63. MG-63 cells in the logarithmic growth phase were collected and cultured with different concentrations of artesunate (12.5 µg/mL, 25 µg/mL and 50 µg/mL) for 24 h, 48 h and 72 h. The total number of MG-63 cells and the morphological changes were observed under an inverted microscope. The MTT assay was adopted to test the inhibition rate (IR) of cell growth. The apoptosis rate was detected using annexin V/propidium iodide (PI) staining. Cell cycle distribution was identified by flow cytometry (FCM), and the expression levels of β-catenin, cyclins and cyclin dependent kinases (CDKs) were measured using Western blotting. The results of the MTT assay indicated that artesunate could remarkably inhibit MG-63 cell proliferation compared with the rates in the untreated control group (0 µg/mL artesunate), and the inhibitory effect was dose-dependent. The apoptosis rate of MG-63 cells was elevated as the concentration of artesunate increased, and all the rates were significantly higher than that in the control group. Additionally, as the artesunate concentration increased, the proportion of MG-63 cells in G0/G1 phase gradually declined whereas that of cells in the G2/M and S phases increased. Western blotting confirmed that a higher concentration of artesunate reduced the expression levels of β-catenin, cyclin A, cyclin D1 and CDK1 and increased the expression levels of cyclin B1; however, artesunate had no impact on CDK2 expression in MG-63 cells. These results demonstrated that artesunate can inhibit β-catenin expression and cell proliferation as well as promote cell apoptosis in MG-63 cells, which indicates that artesunate may serve as a promising drug in the clinical treatment of osteosarcoma. | Counterfeit |
Text : Latent transforming growth factor-β-binding protein (LTBP)2 is a member of the fibrillin/LTBP superfamily of extracellular matrix proteins, and has been demonstrated to exhibit tumor-promoting and tumor-suppressive functions in different types of cancer. However, the function of LTBP2 in gastric cancer (GC) remains unknown. The aim of the present study was to investigate the expression and molecular function of LTBP2 in GC, and to evaluate its prognostic value for patients with GC. The results revealed that the expression of LTBP2 was upregulated in GC tissues and cell lines. Increased LTBP2 expression was associated with poor overall survival in patients with early-stage [tumor-node-metastasis (TNM) I/II] and late-stage (TNM III/IV) GC. Furthermore, silencing of LTBP2 effectively suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition in GC cells. These results suggested that LTBP2 may be considered as a potential therapeutic target and a promising prognostic biomarker for human GC. | Authentic |
Text : Many risk factors of cancer have been established, but the contribution of paternal age in this regard remains largely unexplored. To further understand the etiology of cancer, we investigated the relationship between paternal age and cancer incidence using PLCO cohort. Cox proportional hazards models were performed to assess the association between paternal age and the risk of cancers. During follow-up time (median 11.5 years), 18,753 primary cancers occurred. Paternal age was associated with reduced risk of cancers of the female genitalia (HR, 0.79; 95%CI, 0.66-0.94; P = 0.008) as well as cancers of the respiratory and intrathoracic organs (HR, 0.78; 95%CI, 0.63-0.97; P = 0.026). The association was stronger for lung cancer (HR, 0.67; 95%CI, 0.52-0.86; P = 0.002). The subgroup analysis suggested that age, gender, smoking and BMI were related to the decreased cancer incidence of the respiratory and intrathoracic organs, lung and the female genitalia. Positive linear associations were observed between paternal age and cancer incidence of the female genitalia, respiratory and intrathoracic organs and the lungs. These findings indicate that advanced paternal age is an independent protective factor against various cancers in offspring. | Authentic |
Text : Several studies have noted benign thecoma‑fibroma tumors with positive F‑18 fluorodeoxyglucose (FDG) accumulation mimicking malignant ovarian tumors following F‑18 FDG positron emission tomography (PET). The present study analyzed four cases with false‑positive F‑18 FDG PET/computed tomography (CT) diagnoses of thecoma‑fibroma tumors as malignant tumors due to F‑18 FDG accumulation, compared with eight cases of FDG‑positive ovarian cancers and two cases of FDG‑negative fibromas. Hypoxia inducible factor (HIF)‑1α expression was examined in the six thecoma‑fibroma tumors using reverse transcription‑polymerase chain reaction (RT‑PCR). The four F‑18 FDG‑positive cases exhibited higher cellularity, maximum standard uptake and signal intensity on T2‑weighted imaging, and gadolinium (Gd) enhancement using magnetic resonance imaging than the two FDG-negative fibroma cases. In the F‑18 FDG‑positive thecoma‑fibroma group, Ki‑67 expression was low and LAT1 expression was not identified, ruling out the diagnosis and potential for malignancy. However, considerable glucose transporter 1, HIF‑1α, and vascular endothelial growth factor expression was observed. HIF‑1α expression was elevated in all four false‑positive cases by RT‑PCR. From these results, it was hypothesized that hypoxia due to elevated cellularity may stimulate HIF‑1α expression and be associated with F‑18 FDG accumulation in F‑18‑positive thecoma‑fibroma tumors. | Authentic |
Text : A better understanding of the immune profile of non-small cell lung cancer (NSCLC) and the immunomodulatory impact of chemotherapy is essential to develop current therapeutic approaches. Herein, we collected peripheral blood from 20 healthy donors and 50 patients with advanced NSCLC, before and after chemotherapy, followed by phenotypic analysis of lymphocyte subsets and assessment of the correlation between their post-chemotherapy levels and progression-free survival (PFS). Results showed that, before chemotherapy, the levels of CD8+ lymphocytes, PD-1+CD4+, Th2, and Th17 cells were elevated in patients' peripheral blood, in contrast to natural killer (NK) cells and Th1 cells. Besides, there was no remarkable difference in the frequency of PD-1+CD8+ cells between patients and healthy controls. After chemotherapy, the levels of CD8+ lymphocytes, NK, Th2, Th17, and Treg were declined, in contrast to the level of Th1 cells which was markedly increased. Importantly, chemotherapy had no impact on the frequencies of PD-1+CD8+ and PD-1+CD4+ cells. PFS was significantly better in patients with low percentage of PD-1+CD4+ T cells than those with high percentage. Patients with high content of Th1 cells showed longer PFS than those with low content. The low percentages of Th17 and Treg cells were correlated with longer PFS, even though the difference did not reach statistical significance. In conclusion, the imbalance of lymphocyte subsets is a hallmark of NSCLC. Furthermore, the high level of PD-1+CD4+ cells plays a crucial role in the progression of NSCLC and could be used as a prognostic marker; and the high level of Th1 could predict better clinical outcomes of chemotherapy. | Authentic |
Text : Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer, by Y.-B. Shi, S.-L. Liu, X.-R. Mou, J. Liao, J.-P. Che, X.-Q. Fei, A.-R. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1243-1249-DOI: 10.26355/eurrev_202002_20177-PMID: 32096154" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20177. | Authentic |
Text : Adoptive cell therapy using patients' own T-cells is expected to be an ideal cancer treatment strategy with excellent antitumor effects and low side effects. However, this therapy targeting solid tumors is unlikely to be effective because tumor tissues have an environment that suppresses T-cell function. In particular, interaction between programmed death-1 (PD-1) and its ligand (PD-L1) inhibits T-cell activation by which T-cells eliminate tumor cells. Here, we attempted to develop T-cells that can exert potent antitumor activity even in tumor tissues by genetically modifying them to express the anti-PD-L1 membrane-anchoring type single chain variable fragment (M-scFv) that can inhibit PD-L1/PD-1 interaction. Anti-PD-L1 M-scFv could be expressed on T-cells while maintaining PD-L1-binding ability. Although T-cell proliferation induced by CD3 stimulation was decreased depending on the PD-L1 stimulation intensity, M-scFv-expressing T-cells showed high proliferative activity even in the presence of PD-L1 by avoiding the PD-L1/PD-1-mediated suppression. Furthermore, M-scFv-expressing T-cells showed higher cytotoxic activity against PD-L1high tumor cells than that of mock T-cells. The effect of PD-L1/PD-1 blockade was more pronounced when the therapeutic target was low-antigenic tumor cells with low major histocompatibility complex expression, presenting only the shared antigen. These results indicated that anti-PD-L1 M-scFv expression was functional in avoiding T-cell dysfunction by PD-L1/PD-1 interaction. Our concept of anti-PD-L1 M-scFv-expressing T-cells is thus expected to improve the efficacy of T-cell therapy and contribute to simplify the treatment system and reduce treatment costs compared with the combination therapy of T-cells and antibodies. | Authentic |
Text : Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer‑related mortality worldwide. An increasing number of studies have demonstrated that microRNAs may be used as diagnostic, therapeutic and prognostic targets for human cancers, including HCC. The present study aimed to evaluate microRNA (miR)‑302a expression and function in HCC, and its underlying mechanisms. The results revealed that miR‑302a was expressed at low levels in HCC tissues and cell lines. Reduced miR‑302a expression was correlated with tumor‑node‑metastasis stage and lymph node metastasis in patients with HCC. Additionally, overexpression of miR‑302a reduced cell proliferation and invasion, and induced apoptosis in HCC cells. Vascular endothelial growth factor A (VEGFA) was demonstrated to be a direct target gene of miR‑302a. VEGFA was highly expressed in HCC tissues and inversely correlated with miR‑302a expression. Knockdown of VEGFA expression led to reduced HCC cell proliferation and invasion, and increased apoptosis rates, similar to miR‑302a overexpression, which suggested that VEGFA may be a functional downstream target of miR‑302a in HCC. These data suggested that this newly identified miR‑302a/VEGFA axis may be involved in HCC formation and progression. The present results also provide novel potential targets for the treatments of patients with HCC. | Authentic |
Text : To investigate the influence of tumor necrosis factor-stimulated gene-6 (TSG-6) secreted by bone mesenchymal stem cells (BMSCs) on blood brain barrier (BBB) after intracerebral hemorrhage (ICH) and its related mechanisms. BMSCs and astrocytes were isolated and induced by TNF-α and LPS respectively. The effect of TSG-6 secreted by BMSCs on the proliferation and apoptosis of astrocytes and inflammatory response were assessed by CCK8, flow cytometry, and ELISA respectively. Then we studied the effects of TSG-6 secreted by BMSCs through the paracrine mechanism on the integrity of BBB after ICH via NF-κB signaling pathway in vitro and in vivo. We successfully isolated BMSCs and astrocytes. After LPS treatment of astrocytes, IL-1β, IL-6, and TNF-α showed an upward trend. TSG-6 secreted by TNF-α-activated BMSCs could antagonize the inflammatory response in activated astrocytes. Through the co-culture of astrocytes and BMSCs and the ICH animal model, we found that TSG-6 regulates activated astrocytes by inhibiting the NF-κB signaling pathway and ameliorates BBB damage. Furthermore, we found that TNF-α-activated BMSCs secreted exosomes containing TSG-6 and played an anti-inflammatory effect. TSG-6 secreted by BMSCs regulates activated astrocytes by inhibiting the NF-κB signaling pathway, thereby ameliorating BBB damage. | Authentic |
Text : A methanolic extract of propolis obtained in Myanmar was found to inhibit PANC-1 human pancreatic cancer cells preferentially under nutrient-deprived conditions (NDM), with a PC(50) value of 9.3 microg/mL. Bioactivity-guided fractionation of the extract led to the isolation of two new cycloartane-type triterpenes, (22Z,24E)-3-oxocycloart-22,24-dien-26-oic acid (1) and (24E)-3-oxo-27,28-dihydroxycycloart-24-en-26-oic acid (2), together with 13 cycloartanes (3-13) and four known prenylated flavanones (14-17). Among these, compound 1 exhibited the most potent preferential cytotoxicity (PC(50) 4.3 microM) in a concentration- and time-dependent manner. Furthermore, 1 induced apoptosis-like morphological changes of PANC-1 cells within 24 h of treatment. | Authentic |
Text : Potentilla discolor has been used in traditional Chinese medicine for the treatment of hyperglycemia. However, the potential role of Potentilla discolor against cancer and its mode of action remain to be fully elucidated. The present study explored the apoptotic effect of methanol extract of Potentilla discolor (MEPD) in human mucoepidermoid carcinoma (MEC) cell lines of salivary glands. MEPD markedly suppressed the growth and induced apoptotic cell death in MC3 and YD15 cells. MEPD treatment significantly upregulated the expression of PUMA and reduced STAT3 phosphorylation. Overexpression of STAT3 partially recovered the growth of MEC cells inhibited by MEPD. In addition, dephosphorylation of STAT3 by cryptotanshinone (a potent STAT3 inhibitor) was sufficient to inhibit the growth of MEC cells and induce apoptosis via affecting PUMA protein. These results suggest that MEPD has a potential anticancer property via the STAT3/PUMA signaling axis in human MEC cells of salivary gland. | Authentic |
Text : Numerous microRNAs (miRs) have been implicated in breast cancer; however, the molecular mechanism is not fully understood. The present study examined the function and regulatory mechanism of miR‑181 in breast cancer. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to examine the RNA and protein expression. MTT assay, wound healing assay and transwell assay were conducted to study cell proliferation, migration and invasion. Luciferase reporter gene assay was used to confirm targeting relationship. The results suggested that the miR‑181 expression levels were significantly higher in breast cancer cell lines and clinical tissue samples. The increased expression of miR‑181 was markedly associated with higher clinical stage and lymph node metastasis. The patients with high miR‑181 expression demonstrated worse prognosis compared with those with a low expression of miR‑181. Small interfering RNA‑induced miR‑181 downregulation significantly inhibited breast cancer cell proliferation, migration and invasion in vitro, and tumor growth in vivo. Protein sprouty homolog 4 (SPRY4), downregulated in breast cancer tissues and cell lines, was observed to be a novel target gene of miR‑181. Downregulation of SPRY4 was significantly associated with breast cancer progression in addition to poor prognosis. Knockdown of SPRY4 rescued the inhibitory effects of miR‑181 downregulation on the malignant phenotypes of breast cancer cells. Thus, the present study demonstrated that miR‑181 serves a promoting role in breast cancer at least in part through the inhibition of SPRY4 expression. The present results expand the understanding of the miR‑181/SPRY4 axis' function during for the malignant progression of breast cancer. | Counterfeit |
Text : Recent studies have discovered a class of long non-coding RNAs (lncRNAs) which are dysregulated in various tumors and linked to carcinogenesis. This paper aimed to uncover the molecular functions of lncRNA CASC15 in glioma tumorigenesis. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect CASC15 expression in 50 glioma samples and 4 glioma cells. Besides, proliferation assay, transwell assay and wound healing assay were performed to explore the role of CASC15 in glioma progression in vitro. Furthermore, the interaction between CASC15 and miR-130b-3p in glioma was studied by performing the Dual-Luciferase reporter assay. In addition, tumor formation and metastasis assay were performed in vivo. CASC15 expression was remarkably upregulated in glioma samples compared with that in adjacent samples. Cell proliferation, invasion and migration in glioma were inhibited via knockdown of CASC15 in vitro. Moreover, miR-130b-3p was upregulated via knockdown of CASC15 in vitro. Besides, miR-130b-3p was a direct target of CASC15 in glioma. Tumor formation and metastasis were inhibited after CASC15 was knockdown in vivo. These results suggest that CASC15 could repress metastasis and proliferation of glioma by sponging miR-130b-3p in vitro and in vivo, which may offer a new therapeutic intervention for glioma patients. | Authentic |
Text : In recent years, long non-coding RNAs (lncRNAs) have attracted much attention because of its regulatory role in occurrence and progression of tumors, including triple-negative breast cancer (TNBC). LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) has been explored in some cancers, whereas its function and molecular mechanism in TNBC remain unclear. PITPNA-AS1 expression in TNBC tissues and cells was determined by RT-qPCR. TNBC cell viability, proliferation, migration, invasion were assessed with CCK-8, colony formation, wound healing, transwell assays. Cell apoptosis was evaluated by flow cytometry. Expression of EMT-related markers was detected by western blot analyses. The molecular mechanism of PITPNA-AS1 was explored by RNA pull down, luciferase reporter, RIP and ChIP assays. PITPNA-AS1 showed high expression levels in TNBC tissues and cells. PITPNA-AS1 knockdown suppressed TNBC cell viability, proliferation, migration, invasion in vitro and inhibited xenograft tumor growth in mice. Mechanistically, PITPNA-AS1 upregulated SIK2 expression by sponging miR-520d-5p and recruiting DDX54 protein. Results of rescue assays suggested that the inhibitive effects of silenced PITPNA-AS1 on TNBC cellular processes were partially rescued by overexpressing SIK2 or combination of miR-520d-5p inhibition and DDX54 overexpression. More importantly, we found that the upregulation of PITPNA-AS1 in TNBC cells was attributed to transcription factor MYBL2. PITPNA-AS1 activated by MYBL2 plays an oncogenic role in TNBC through upregulating SIK2. | Authentic |
Text : Survivin is highly expressed in fetal tissue and is completely absent in terminally differentiated cells, but its re-expression has been observed in most human tumors. Presently, we aimed to analyze the possible impact of the survivin gene (-31G > C, rs 9904341) promoter polymorphism on the expression profile of survivin gene and ultimately the role of survivin re-expression in the development and progression of non-small cell lung cancer. A case-control study of 100 non-small cell lung cancer patients and 100 cancer-free healthy controls was conducted. Survivin gene promoter polymorphism was analyzed by PCR-restriction fragment length polymorphisms (RFLP) technique, and the survivin expression profile was evaluated using quantitative real-time PCR assay. Compared to the survivin GG genotype, odd ratio of 3.2 (95 % CI 4.8-25.9, p = 0.004) was found to be associated to homozygous CC genotype with 15-fold increase of survivin gene expression in non-small cell lung cancer patients. Significant trend of increase in survivin expression was observed with the increase in severity of the disease. Patients with survivin (-31CC) genotype had significantly shorter overall survival compared to survivin (-31GG) genotype carriers. In addition, advanced disease status and significant poor overall survival were also reflected by patients with higher-fold increase in survivin gene expression. In conclusion, present study demonstrated that survivin (-31G > C) polymorphism may contribute to the risk of developing non-small cell lung cancer in Indian population. Survivin (-31CC) genotype was associated with significantly increased survivin gene expression and ultimately may contribute in the poor clinical outcome of non-small cell lung cancer patients, suggesting its possible significance in the development and progression of non-small cell lung cancer. | Authentic |
Text : Long non-coding RNAs (lncRNAs) are associated with a spectrum of biological processes such as gene regulation on transcriptional and post-transcriptional levels. The HOXA transcript at the distal tip (HOTTIP) lncRNA plays an important role in carcinogenesis; however, the underlying role of HOTTIP in colorectal carcinoma (CRC) remains unknown. The aim of the present study was to evaluate the expression and function of HOTTIP in CRC. In the present study, we analyzed HOTTIP expression levels of CRC patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown of HOTTIP by RNA interference was performed to explore its roles in cell proliferation, migration, and invasion. Our results found that HOTTIP was upregulated in human primary CRC tissues. Knockdown of HOTTIP inhibited CRC cell proliferation, migration, and invasion. Above all, knockdown of HOTTIP could represent a rational therapeutic strategy for CRC. | Authentic |
Text : Colorectal cancer is one of most common tumors in developed countries and, despite improvements in treatment and diagnosis, mortality rate of patients remains high, evidencing the urgent need of novel biomarkers to properly identify colorectal cancer high-risk patients that would benefit of specific treatments. Recent works have demonstrated that the telomeric protein TRF2 is over-expressed in colorectal cancer and it promotes tumor formation and progression through extra-telomeric functions. Moreover, we and other groups evidenced, both in vitro on established cell lines and in vivo on tumor bearing mice, that TRF2 regulates the vascularization mediated by VEGF-A. In the present paper, our data evidence a tight correlation between TRF2 and VEGF-A with prognostic relevance in colorectal cancer patients. For this study we sampled 185 colorectal cancer patients surgically treated and diagnosed at the Regina Elena National Cancer Institute of Rome and investigated the association between the survival outcome and the levels of VEGF-A and TRF2. Tissue microarray immunohistochemical analyses revealed that TRF2 positively correlates with VEGF-A expression in our cohort of patients. Moreover, analysis of patients' survival, confirmed in a larger dataset of patients from TCGA, demonstrated that co-expression of TRF2 and VEGF-A correlate with a poor clinical outcome in stage I-III colorectal cancer patients, regardless the mutational state of driver oncogenes. Our results permitted to identify the positive correlation between high levels of TRF2 and VEGF-A as a novel prognostic biomarker for identifying the subset of high-risk colorectal cancer patients that could benefit of specific therapeutic regimens. | Authentic |
Text : Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), also known as fibulin-4, MBP1 and UPH1, is an extracellular matrix protein associated with a variety of tumors. The purpose of this study was to investigate the prognostic value and the function of EFEMP2 in lung cancer. The mRNA and protein expression of EFEMP2 in lung normal and cancer tissues, lung cancer cell lines (A549, H460, H1299 and H1650) and normal epithelial cell line BEAS-2B were evaluated by immunohistochemistry, RT-qPCR and Western blotting. The Public databases (Oncomine and Kaplan-Meier plotter) were used to investigate the prognostic value of EFEMP2 in lung cancer. RNA interference (RNAi) and overexpression transfection were performed to detect the effects of EFEMP2 up- or down-regulation on lung normal and cancer cell proliferation, invasion and metastasis in vitro and in vivo. EFEMP2 was lowly expressed in lung cancer tissues and cells, and its low expression was associated with malignant phenotype and poor prognosis of lung cancer. The same conclusion had been drawn from the Public databases. EFEMP2 overexpression significantly inhibited the invasion of lung cancer cells, hampered the process of EMT, and decreased the expression and activity of MMP2 and MMP9, while EFEMP2 knockdown remarkably enhanced the invasion of lung cancer cells, promoted EMT, and increased the expression and activity of MMP2 and MMP9. The low expression of EFEMP2 was detected in lung cancer and was positively correlated with the poor prognosis of patients. EFEMP2 was a tumor suppressor gene that inhibited the progress of lung cancer, which suggested a new research objective for the future studies. | Authentic |
Text : Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib. Crizotinib was initially designed as a MET inhibitor, whereas alectinib is a selective ALK inhibitor. The MET signal, which is inhibited by crizotinib but not by alectinib, is dysregulated in many human cancers. However, the role of the MET signal in ALK-positive NSCLC remains unclear. In this study, we found that hepatocyte growth factor (HGF), ligand of MET, mediated the resistance to alectinib, but not to crizotinib, via the MET signal in ALK-positive NSCLC cell lines (H3122 and H2228 cell lines). In addition, alectinib activated the MET signal even in the absence of HGF and the inhibition of the MET signal enhanced the efficacy of alectinib. These findings suggest that activated MET acts as a salvage signal in ALK-positive NSCLC. This novel role of the MET signal in ALK-positive NSCLC may pave the way for further clinical trials examining MET inhibitors. | Authentic |
Text : Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) is a corepressor for the transcription factor PBX. Previous studies showed that HPIP is frequently overexpressed in many tumors. However, the role of HPIP in head-and-neck squamous cell carcinoma (HNSCC) has not yet been determined. Thus, we decided to investigate the effects and mechanisms of HPIP in HNSCC. Our results demonstrated that HPIP is highly expressed in human HNSCC cell lines and provides the first evidence that knockdown of HPIP obviously inhibits proliferation and migration/invasion in HNSCC cells in vitro, as well as inhibits tumor growth in vivo. Furthermore, knockdown of HPIP significantly inhibits the expression of p-PI3K and p-Akt in human HNSCC cells. In conclusion, our study demonstrated that knockdown of HPIP significantly inhibits the proliferation and migration/invasion of HNSCC cells by suppressing the PI3K/Akt signaling pathway. Therefore, HPIP may be a novel potential therapeutic target for the treatment of HNSCC. | Authentic |
Text : Activin receptor‑like kinases (ALKs), members of the type I activin receptor family, belong to the serine/threonine kinase receptors of the transforming growth factor‑β (TGF‑β) superfamily. ALKs mediate the roles of activin/TGF‑β in a wide variety of physiological and pathological processes, ranging from cell differentiation and proliferation to apoptosis. For example, the activities of ALKs are associated with an advanced tumor stage in prostate cancer and the chondrogenic differentiation of mesenchymal stem cells. Therefore, potent and selective small molecule inhibitors of ALKs would not only aid in investigating the function of activin/TGF‑β, but also in developing treatments for these diseases via the disruption of activin/TGF‑β. In recent studies, several ALK inhibitors, including LY‑2157299, SB‑431542 and A‑83‑01, have been identified and have been confirmed to affect stem cell differentiation and tumor progression in animal models. This review discusses the therapeutic perspective of small molecule inhibitors of ALKs as drug targets in tumor and stem cells. | Authentic |
Text : The activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling and upregulation of excision repair cross complementation group 1 (ERCC1) are the two most important factors that confer resistance to cisplatin (DDP) therapy in non-small-cell lung cancer (NSCLC). Therefore, inhibition of the PI3K/Akt/mTOR signaling pathway and ERCC1 expression is a potential approach for the treatment of patients with advanced NSCLC. In the present study, whether combined treatment with DDP and BEZ235, a dual PI3K/mTOR inhibitor, could provide a synergistic antitumor effect in A549/DDP cells was investigated, and the possible mechanisms involved were explored. The half-maximal inhibitory concentration (IC50) values were calculated in A549/DDP cells. Synergistic interaction of BEZ235 and DDP was evaluated by combination index (CI) analysis. The levels of phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), apoptosis-related proteins and ERCC1 were detected by western blot analysis. Apoptotic cells were quantified by flow cytometry and Hoechst 33342 staining. The migration and invasion abilities of A549/DDP cells were evaluated by wound healing and Transwell assays, respectively. It was observed that the dose reduction index (DRI) of BEZ235 was 13.82 and for DDP it was 13.58, and the CI of combination was <1 over a wide range of doses. In addition, the levels of p-Akt, p-mTOR and ERCC1 were significantly elevated by DDP treatment, and were reduced by co-administration of BEZ235 and DDP. Furthermore, the combination treatment significantly induced apoptotic cell death, decreased migration and invasion abilities compared with those treated with either BEZ235 or DDP alone. In conclusion, the combination of BEZ235 with DDP had synergistic antitumor effects in A549/DDP cells as reflected by reduced proliferation, increased apoptosis, and suppression of the migration and invasion abilities of A549/DDP cells, and the mechanism mediating these effects may be associated with the inhibition of PI3K/Akt/mTOR signaling and down-regulation of ERCC1 expression. | Authentic |
Text : The purpose of this study was to investigate the inhibitory effect of baicalein on the proliferation of cervical carcinoma cells and stimulate cervical carcinoma cells with baicalein. MTT method was used to observe cell proliferation. Flow cytometry was used to observe cell cycle, and gene technology was used to observe the expression of corresponding genes at the level of gene and protein. β-catenin activity was assessed using Western blot and ChIP. Baicalein suppressed cervical carcinoma cell HeLa proliferation by enhancing the activity of caspase-3. Baicalein blocked cell cycle at G0/G1 stage by inhibiting the expression of some genes. At the same time, it can prevent the nuclear translocation of β-catenin and inhibit the activity of Wnt. When the Wnt signaling pathway is increased, the proliferation of HeLa cells is inhibited, and apoptosis is promoted in this way. In conclusion, it indicated that baicalein inhibits cervical carcinoma progression by targeting CCND1 via Wnt/β-catenin signaling pathway. | Authentic |
Text : Background: Ovarian cancer (OC) represents the seventh most lethal female tumors worldwide. The combination of PARP inhibitor (PARPi) and angiogenic inhibitor has been shown to be effective as a first-line or second-line maintenance regimen to synergistically exert antitumor effects, which prompts us to further evaluate the therapeutic effect of the combination of PARP inhibitor Niraparib and anti-angiogenic Brivanib on OC. Method:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay were applied to evaluate the anti-proliferative effect of Niraparib, Brivanib, or the combination treatment on OC cells. The Annexin V-FITC/PI apoptotic assay was adopted to detect cell apoptosis. Tumor xenograft experiment and immunohistochemical (IHC) analysis were performed to evaluate the effect of single or combination treatment on the tumorigenicity of OC in vivo. Results: Our current findings revealed that OC cells harboring BRAC1/2 mutations were more sensitive to Niraparib treatment compared to those with BRAC wild-type, and the addition of Brivanib enhanced programmed cell death (PCD) to sensitize OC cells with BRAC mutations to Niraparib treatment in vitro and in vivo. Conclusion: Our work illustrates that the combination regimen of PARPi and angiogenic inhibitor treatment should be beneficial for the OC patients with BRAC mutations, at least partially owing to the induction of multiple forms of programmed cell death (PCD). | Authentic |
Text : Four new annonaceous acetogenins (ACGs), squamocin-I (1), II (2) and III (3) and squamoxinone-D (4), together with seven known ACGs (5-11), were isolated from the seeds of Annona squamosa. The structures of all isolates were elucidated and characterised by spectral and chemical methods. Compounds 1-4 were evaluated for their cytotoxicities against Hep G2, SMMC 7721, BEL 7402, BGC 803 and H460 human cancer cell lines. Compound 1 exhibited better potent activity than the positive compound and compound 3 shows selectively cytotoxical activity against H460 with IC50 values of 0.0492 μg/ml. | Counterfeit |
Text : MicroRNAs (miRNAs) have emerged as critical regulators in cancer progression. miR‑613 has been reported as a tumor suppressor gene in many types of human cancers. However, the function of miR‑613 in renal cell carcinoma (RCC) remains unclear. In the present study, the authors aimed to detect the expression of miR‑613 and its function in RCC cell lines. miR‑613 was reported to be significantly downregulated RCC cell lines. Functional analyses demonstrated that overexpression of miR‑613 significantly decreased RCC cell proliferation and invasion. Bioinformatics analysis showed that Frizzled7 (FZD7) was a predicted target of miR‑613, which was verified by dual‑luciferase reporter assay, reverse transcription quantitative‑polymerase chain reaction and western blot analysis. Restoration of FZD7 significantly reversed the suppressive effects of miR‑613 on RCC cell proliferation and invasion. Taken together, the results of the present study indicated that miR‑613 functions as a tumor suppressor that inhibits RCC cell proliferation and invasion by targeting and inhibiting FZD7, providing novel insight into RCC pathogenesis and a potential therapeutic target for RCC. | Authentic |
Text : The purpose of this study was to elucidate the potential influence of LINC01605 on the progression of laryngeal squamous cell carcinoma (LSCC) and the underlying mechanism. LINC01605 and microRNA-493-3p (miR-493-3p) levels in normal laryngeal tissues, LSCC tissues, and paired paracancerous tissues were detected. Regulatory effects of LINC01605 on proliferative ability and apoptosis in HEp-2 and AMC-HN-8 cells were assessed. Besides, the interaction between LINC01605 and miR-493-3p was evaluated by Dual-Luciferase reporter gene assay and Spearman's rank correlation analysis. Finally, rescue experiments were conducted to clarify the role of LINC01605/miR-493-3p axis in the progression of LSCC. LINC01605 was upregulated and miR-493-3p was downregulated in LSCC tissues. Knockdown of LINC01605 inhibited proliferative ability, and stimulated apoptosis in HEp-2 and AMC-HN-8 cells. Moreover, LINC01605 directly bound to miR-493-3p, and the former negatively regulated the level of the latter. In addition, miR-493-3p was able to reverse the regulatory effect of LINC01605 on proliferative ability in LSCC. LINC01605 is upregulated in LSCC tissues, and it promotes the malignant progression of LSCC via targeting miR-493-3p. | 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 : Gastric cancer (GC) patients develop malignant ascites as the disease progresses owing to peritoneal metastasis. GC patients with malignant ascites have a rapidly deteriorating clinical course with short survival following the onset of malignant ascites. Better optimized treatment strategies for this subset of patients are needed. To define the cellular characteristics of malignant ascites of GC, we used single-cell RNA sequencing to characterize tumor cells and tumor-associated macrophages (TAMs) from four samples of malignant ascites and one sample of cerebrospinal fluid. Reference transcriptomes for M1 and M2 macrophages were generated by in vitro differentiation of healthy blood-derived monocytes and applied to assess the inflammatory properties of TAMs. We analyzed 180 cells, including tumor cells, macrophages, and mesothelial cells. Dynamic exchange of tumor-promoting signals, including the CCL3-CCR1 or IL1B-IL1R2 interactions, suggests macrophage recruitment and anti-inflammatory tuning by tumor cells. By comparing these data with reference transcriptomes for M1-type and M2-type macrophages, we found noninflammatory characteristics in macrophages recovered from the malignant ascites of GC. Using public datasets, we demonstrated that the single-cell transcriptome-driven M2-specific signature was associated with poor prognosis in GC. Our data indicate that the anti-inflammatory characteristics of TAMs are controlled by tumor cells and present implications for treatment strategies for GC patients in which combination treatment targeting cancer cells and macrophages may have a reciprocal synergistic effect. | Authentic |
Text : Liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) are both considered as radical treatments for small hepatocellular carcinoma (HCC). However, it is still unclear whether to select LR or PMCT in HCC patients with different degrees of liver cirrhosis. The purpose of this study was to compare the efficacy of LR and PMCT in the treatment of solitary and small HCC accompanied with different degrees of liver cirrhosis. In this study, 230 patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 108 received PMCT. The short- and long-term outcomes were compared between these two procedures. Severity of liver cirrhosis was evaluated by using clinical scoring system (CSS) as previously published. Subgroup analysis based on CSS was performed to evaluate the effect of severity of liver cirrhosis on surgical outcomes after LR and PMCT. There was no mortality within 90 days in both groups. Major complications were significantly more frequent in the LR group than in the PMCT group (18.8% vs. 4.6%, p<0.001). However, LR provided better surgical outcomes than PMCT. The 5-year overall survival (OS) rates for the LR and PMCT groups were 65.2% and 42%, respectively (p=0.006), and the corresponding disease-free survival (DFS) rates were 51.7% and 31.5%, respectively (p=0.004). Nevertheless, subgroup analysis showed that PMCT provided long-term outcomes that were similar to LR and lower surgical complications in HCC patients with CSS score≥4. LR may provide better OS and DFS rates than PMCT for patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function irrespective of liver cirrhosis. PMCT should be viewed as the optimal treatment for solitary and small HCC with severe cirrhosis. | Authentic |
Text : Prostate cancer remains a significant cause of cancer-related deaths in male population. More recently, accumulating evidence continues to implicate long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in various types of cancers, including prostate cancer. The current study aimed to elucidate the role of lncRNA AGAP2-AS1/miR-195-5p/PDZ and LIM domain 5 (PDLIM5) in prostate cancer progression. Initially, microarray expression profiles were applied to screen differentially expressed lncRNAs/miRNAs/genes associated with prostate cancer. Dual-luciferase reporter and RNA pull-down/RIP assays were subsequently performed to explore the interactions among lncRNA AGAP2-AS1, miR-195-5p, and PDLIM5, after which their expression was detected in cancer tissues and cells. Next, gain- and loss-of-function approaches were employed to elucidate the mechanism of lncRNA AGAP2-AS1/miR-195-5p/PDLIM5 in the processes of cell proliferation, migration and invasion as well as tumor growth. LncRNA AGAP2-AS1 was found to be highly expressed in prostate cancer. Silencing of lncRNA AGAP2-AS1 contributed to the suppression of proliferation, migration and invasion of cancer cells in vitro. Besides, lncRNA AGAP2-AS1 could bind to miR-195-5p which targeted PDLIM5 and subsequently downregulated its expression, ultimately impeding the progression of prostate cancer. Additionally, lncRNA AGAP2-AS1 inhibition led to an up-regulated expression of miR-195-5p and down-regulated PDLIM5 expression, resulting in delayed tumor growth in vivo. Taken together, the key findings of our study demonstrated that lncRNA AGAP2-AS1 silencing exerted suppressive effects on the development of prostate cancer via the miR-195-5p-dependent downregulation of PDLIM5. Our findings highlighted the potential of lncRNA AGAP2-AS1 as a promising novel molecular target for prostate cancer therapy. | Counterfeit |
Text : Objective: In China, cancer accounts for one-fifth of all deaths, and exerts a heavy toll on patients, families, healthcare systems, and society as a whole. This study aims to examine the temporal trends in socio-economic and rural-urban differences in treatment, healthcare service utilization and catastrophic health expenditure (CHE) among adult cancer patients in China. We also investigate the relationship between different types of treatment and healthcare service utilization, as well as the incidence of CHE. Materials and Methods: We analyzed data from the 2011 and 2015 China Health and Retirement Longitudinal Study, a nationally representative survey including 17,224 participants (234 individuals with cancer) in 2011 and 19,569 participants (368 individuals with cancer) in 2015. The study includes six different types of cancer treatments: Chinese traditional medication (TCM); western modern medication (excluding TCM and chemotherapy medications); a combination of TCM & western medication; surgery; chemotherapy; and radiation therapy. Multivariable regression models were performed to investigate the association between cancer treatments and healthcare service utilization and CHE. Results: The age-adjusted prevalence of cancer increased from 1.37% to 1.84% between 2011 and 2015. More urban patients (54%) received cancer treatment than rural patients (46%) in 2015. Patients with high socio-economic status (SES) received a higher proportion of surgical and chemotherapy treatments compared to patients with low SES in 2015. Incidence of CHE declined by 22% in urban areas but increased by 31% in rural areas. We found a positive relationship between cancer treatment and outpatient visits (OR = 2.098, 95% CI = 1.453, 3.029), hospital admission (OR = 1.961, 95% CI = 1.346, 2.857) and CHE (OR = 1.796, 95% CI = 1.231, 2.620). Chemotherapy and surgery were each associated with a 2-fold increased risk of CHE. Conclusions: Significant improvements in health insurance benefit packages are necessary to ensure universal, affordable and patient-centered health coverage for cancer patients in China. | Authentic |
Text : MicroRNAs are short regulatory RNAs that posttranscriptionally modulate gene expression and thus play crucial roles in controlling cancer-onset, growth, and progression processes. miR107, a highly conserved microRNA that maps to intron 5 of the PANK1 gene, contributes to the regulation of normal and tumor biological processes. Studies have reported that miR107 has oncogenic or tumor-suppressor functions in different human tumors. The pleiotropic functions of miR107 in various cancers are achieved via its targeting different genes that are involved in tumor proliferation, invasiveness, metastasis, angiogenesis, and chemotherapy-response pathways. The carcinogenicity or cancer-suppressor effects of miR107 occur in a tissue- and cell-specific manner, and the expression level of miR107 can be affected by various factors, including epigenetic and genetic factors, treatment exposure, and daily diet. A comprehensive analysis of the current literature suggests that miR107 functions as a central element in the regulation of cancer networks and can be used as a potential diagnostic and prognostic biomarker and drug target for therapeutic intervention. | Authentic |
Text : Phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) is required for protein kinase B (AKT) activation. The level of PI(3,4,5)P3 is constantly regulated through balanced synthesis by phosphoinositide 3-kinase (PI3K) and degradation by phosphoinositide phosphatases phosphatase and tensin homologue (PTEN) and SH2-domain containing phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 (SHIP2), known as negative regulators of AKT. Here, I show that SHIP2 inhibition in cervical cancer cell lines alters H2 O2 -mediated AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway activation. In addition, SHIP2 inhibition enhances reactive oxygen species generation. Interestingly, I found that SHIP2 inhibition and H2 O2 treatment enhance lipid and protein phosphatase activity of PTEN. Pharmacological targeting or RNA interference(RNAi) mediated knockdown of PTEN rescues extracellular signal-regulated kinase and AKT activation. Using a series of pharmacological and biochemical approaches, I provide evidence that crosstalk between SHIP2 and PTEN occurs upon an increase in oxidative stress to modulate the activity of mitogen-activated protein kinase and phosphoinositide 3/ATK pathways. | Authentic |
Text : Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a membrane glycoprotein expressed by activated effector T cells (Teffs) and participates in the repression of T cell proliferation, cell cycle progression and cytokine production. Currently, antibodies targeting CTLA-4, ipilimumab and tremelimumab are widely used as a therapeutic approach in a variety of human malignancies. However, their detailed mechanism remains unclear. Therefore, in this review, we focused specifically on recent findings concerning the role of CTLA-4 in immune response and also discussed clinical studies of targeting CTLA-4, alone or in combination with other therapies for the treatment of cancers. CTLA-4 blockade is used as a therapeutic approach for the treatment of cancer through competing with CD28-positive costimulation for binding to their shared B7 ligands or exhibiting direct inhibitory effect on signaling molecules in the cytoplasmic tail. At present, antibodies for targeting CTLA-4 or in combination with other therapies significantly reinforced the anti-tumor effect and improved the prognosis of malignant disease. In addition, severe adverse events of targeting CTLA-4 therapy could be a challenge for the development of this therapeutic strategy. This review may provide some new insights for clinical studies of targeting CTLA-4. | Authentic |
Text : The aim of this study was to investigate whether lncSNHG15 promoted the proliferation and migration of non-small cell lung cancer (NSCLC) cells by binding to miR-211-3p, thereby participating in the development of NSCLC. Expressions of lncSNHG15 and miR-211-3p in NSCLC tissues and para-cancerous tissues were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). LncSNHG15 and miR-211-3p expression in NSCLC cell lines were determined as well. Furthermore, cell counting kit-8 (CCK-8) and transwell assays were performed to evaluate the effects of lncSNHG15 and miR-211-3p on cell proliferation and migration, respectively. The binding relationship between miR-211-3p and ZNF217, as well as between miR-211-3p and lncSNHG15, were further verified by the Luciferase reporter gene assay. In addition, rescue experiments were performed to verify whether lncSNHG15 promoted the proliferation and migration of NSCLC cells by degrading miR-211-3p. The expression of lncSNHG15 in NSCLC tissues was significantly higher than that of para-cancerous tissues. In particular, the expression of lncSNHG15 in NSCLC patients with stage III-IV was higher than those with stage I-II. Furthermore, lncSNHG15 over-expression remarkably promoted the proliferation and migration of NSCLC cells (A549 and H358). The Luciferase reporter gene assay further indicated that lncSNHG15 could bind to miR-211-3p. Simultaneously, miR-211-3p expression in NSCLC tissues was significantly lower than that of para-cancerous tissues. The over-expression of miR-211-3p could inhibit the proliferation and migration of A549 and H358 cells. Meanwhile, the Luciferase reporter gene assay indicated that ZNF217 was the target of miR-211-3p. In addition, the over-expression of ZNF217 reversed the inhibitory effect of miR-211-3p on the proliferative and migratory potentials of A549 and H358 cells. High expression of lncSNHG15 promoted the proliferation and migration of NSCLC cells by upregulating ZNF217 by adsorbing miR-211-3p. | Authentic |
Text : Tumor-associated macrophages (TAMs) are closely related to poor prognosis in triple-negative breast cancer (TNBC). Thus, gaining insight into how TAMs support cancer progression could contribute to effective therapies. We utilized the 4 T1 murine TNBC cell line and murine bone marrow-derived macrophages to assess TAM-mediated pro-proliferative effects in vivo and in vitro. Further, Transcriptional analysis was performed to identify pathways activated in TAM-stimulated 4 T1 cells. We also explored the therapeutic efficacy of combining a mitogen-activated protein kinase kinase (MEK) inhibitor with TAM-targeted therapy using a TNBC mouse model. We found that the presence of TAMs was significantly associated with proliferating cancer cells in a TNBC mouse model. Moreover, RNA sequencing analysis showed that TAMs could enhance mitogen-activated protein kinase (MAPK) pathway activation in 4 T1 cells compared to that in control cells. Further, the depletion of TAMs by clodronate liposomes significantly reduced MAPK pathway activation in vivo. In addition, the blockade of MAPK signaling by a MEK inhibitor repressed TAM-mediated cancer cell proliferation. Most importantly, MEK inhibition combined with macrophage depletion significantly suppressed tumor growth and increased T lymphocyte infiltration in a TNBC model. Our study suggests the possibility that TAM-induced MAPK pathway activation promotes cancer cell proliferation. Thus, MEK inhibition combined with macrophage depletion might represent an effective treatment for TNBC. | Authentic |
Text : Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC. | Authentic |
Text : The aim of this overview study is to familiarize readers with the impact of changes to body image (BI) among patients treated for breast cancer. Body image is subjected to many changes during oncological treatment and every method of treatment (surgery, chemotherapy, radiotherapy, and hormone therapy) can have a negative impact on the way the treated patients perceive their bodies. The article differentiates the susceptibility of patients to a worsened self-image due to their pre-disease personality, socioeconomic factors, age, and declared sense of control during the oncological treatment. Herein, the areas of patients' lives which are the most affected by negative BI are discussed: quality of life and functioning in society, with particular emphasis on the return to work and sexuality. The ways of protecting patients' BI throughout treatment which have been proposed in the literature are presented in conclusions. | Authentic |
Text : The existences of cancer stem cells in patients with pancreatic cancer are considered as pivotal factors contributing to chemoresistance and disease relapse. Glypican-4 (GPC4) is one of the members of the glypicans family, which underlies human congenital malformations and multiple diseases. However, its potential biological function in pancreatic cancer still remains elusive. In this study, we are the first to demonstrate that GPC4 was involved in 5-fluorouracil (5-FU) resistance and pancreatic cancer stemness through comprehensive bioinformatical analysis. Functional experiments showed that knockdown of GPC4 sensitized pancreatic cancer cells to 5-FU and attenuated stem cell-like properties. In terms of mechanism research, knockdown of GPC4 suppressed the activation of Wnt/β-catenin pathway and its downstream targets. Furthermore, the expression of GPC4 was significantly upregulated in pancreatic cancer tissues compared with normal tissues and remarkably correlated with patients' overall survival according to the data derived from the Cancer Genome Atlas database. Taken together, our results suggest that GPC4 is a key regulator in chemoresistance and pancreatic cancer stemness. Thus, targeting GPC4 may serve as a promising strategy for pancreatic cancer therapy. | Authentic |
Text : Prostate cancer is one of the most common malignant tumors. Recently, the role of long noncoding RNAs (lncRNAs) in tumor progression has been well concerned by numerous researchers. In this research, lncRNA TTN-AS1 was studied to identify its biological function in the progression of prostate cancer. Firstly, Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was conducted to measure TTN-AS1 expression in prostate cancer tissues. Furthermore, in vitro role of TTN-AS1 in regulating prostate cancer cells was assessed. Tumor formation assay was conducted in NOD/SCID mice to explore the in vitro function of TTN-AS1. In addition, the luciferase reporter gene assay was performed to analyze the relationship between TTN-AS1 and miR-1271. TTN-AS1 expression was remarkably higher in prostate cancer samples compared with that of corresponding ones. Moreover, proliferation and migration of prostate cancer cells were inhibited after TTN-AS1 was silenced. MiR-1271 was upregulated after the silence of TTN-AS1. Further mechanism assays showed that miR-1271 was a direct target of TTN-AS1 in prostate cancer. In addition, tumor formation and metastasis abilities were inhibited after in vivo knockdown of TTN-AS1. Our study discovers a potential oncogene in prostate cancer and demonstrates that TTN-AS1 enhances cell proliferation and migration via sponging miR-1271. | Counterfeit |
Text : To explore the expression levels of miR-488, miR-29c-3p, and growth differentiation factor 15 (GDF15) in colon cancer tissue and analyze their relationship with clinicopathological features in patients with colon cancer. The study was conducted from November 2012 to November 2020. A total of 200 patients with colon cancer were treated in our hospital during this period. During the operation, the colon cancer tissues and the adjacent tissues whose distance from the cancer tissues were more than 5 cm were collected, and the expression levels of miR-488, miR-29c-3p, and GDF15 mRNA in colon cancer tissues were detected by qRT-PCR (real-time fluorescence quantitative). The relationship between them and the clinicopathological features and prognosis of patients with colon cancer were analyzed and discussed. The level of miR-488 in colon cancer tissues was lower than that in adjacent tissues, but the levels of miR-29c-3p and GDF15 mRNA in colon cancer tissues were higher than those in adjacent tissues (P < 0.05). Compared with paracancerous tissues, the expression rates of miR-29c-3p and GDF15 protein were higher in colon cancer tissues (P < 0.05). There was no difference in age, sex, tumor location, and tumor diameter between high expression of miR-488 group and low expression of miR-488 group (P > 0.05). The degree of differentiation, depth of invasion, TNM stage, lymph node metastasis, and other factors have a direct impact on the level of miR-488 and the expression of miR-29c-3p (P < 0.05). The depth of invasion, TNM stage, and lymph node metastasis could affect the expression of GDF15 in patients with colon cancer (P < 0.05). miR-488, miR-29c-3p, and GDF15 in colon cancer tissue are related to the clinicopathological features of patients in varying degrees and may become markers after early warning of colon cancer, which can provide effective guidance for clinical diagnosis and treatment. | Authentic |
Text : Since DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.XY39ph) may act as a tumour-relevant factor. This study was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for expression of KRas mutated. H2A.X phosphorylation and ERK1/2 was measured, and transwell experiment was performed to examine the consequents of H2A.XY39ph on MP65 cells developing and migration. Regulatory relationship between H2A.XY39ph and ERK1/2 downstream genes were measured. Moreover, whether JMJD6 and MDM2 are involved in H2A.X phosphorylation was studied. Mutation of Ras activated ERK1/2 signalling and inhibited H2A.X phosphorylation at Y39. Silence of H2A.XY39ph contributed to the regulation of MP65 cells growth, migration and transcription of ERK1/2 downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16. The repressed H2A.X phosphorylation through Ras-ERK1/2 signalling might be through MDM2-mediated JMJD6 degradation. Our study suggested that Ras-ERK1/2 signalling inhibited H2A.X phosphorylation at Y39, which led to the uncontrolled developing and migration of uveal melanoma cells. In addition, H2A.X phosphorylation was mediated possibly through JMJD6 which could be degraded by MDM2. | Counterfeit |
Text : This study was conducted in order to explore the role that Bmi-1 plays during the development of a gastrointestinal stromal tumor (GIST) by regulation of the p16Ink4A and p14ARF expressions. Eighty-six patients diagnosed with GIST were selected to take part in this experiment. The Bmi-1 protein expressions in GIST and adjacent normal tissues were detected using immunohistochemistry and further analyzed by using photodensitometry. To monitor and track the progression of the GIST, a 3-year follow-up was conducted for all affected patients. After cell transfection, the GIST cells were assigned into the control group (without transfection), the negative control (NC) group (transfected with Bmi-1-Scramble plasmid), and the Bmi-1 shRNA group (transfected with the pcDNA3.1-Bmi-1 shRNA plasmid). Protein and mRNA expressions collected from Bmi-1, p16lnk4A, P14ARF, cyclin D1, and CDK4 were measured using both the RT-qPCR and western blotting methods Cell senescence was assessed and obtained by using the β-Galactosidase (β-Gal) activity assay. The use of a Soft agar colony formation assay and CCK-8 assay were performed in order to detect the cell growth and subsequent proliferation. Cell invasion and migration were analyzed using the Transwell assay and scratch test. Bmi-1 in the GIST tissues was found to be significantly higher and the p16lnk4A and P14ARF expressions were lower than those in the adjacent normal tissues. Bmi-1 was negatively correlated with p16lnk4A and P14ARF expressions according to the correlation analysis. Bmi-1 expression was associated with the TNM stage, postoperative recurrence, metastasis, tumor size, and the 5-year survival rate. Area under ROC curve was calculated at 0.884, and sensitivity, specificity, and accuracy of Bmi-1 predicting the GIST were 67.44%, 97.67%, and 65.12%, respectively. Patients exhibiting a high Bmi-1 expression in the GIST tissues had lower survival rates than those with low Bmi-1 expression. In comparison with the control group, P14ARF, and p16lnk4A were up-regulated, while cyclinD 1 and CDK4 were down-regulated, cell senescence was promoted, and cell proliferation, invasion, and migration also showed some regression in the Bmi-1 shRNA group. These collection of data indicated that the down-regulated Bmi-1 might inhibit the proliferation, invasion, and migration of GIST cells and can be subsequently linked to the incidence and developing a prognosis of GIST. | Counterfeit |
Text : Colon cancer is one of the most malignant cancers. Histone modification is closely related to tumour development. Our study explored the functions of anti-silencing function 1A (ASF1A) on H4Y72ph in colon cancer cells. Colon cancer cell lines and clinical specimens were obtained and/or transfected with full length ASF1A or interference mRNA to mimic or silence of ASF1A expression. Immunoprecipitation and GST pull down was used to target targeting ASF1A or H4Y72ph. Cells were transfected with H4WT- or H4Y72F-expressing. An in vitro kinase activity assay was set to determine whether ASF1A could phosphorylate H4. The severity of autophagy was measured by detecting number of autophagosomes, number of EGFP-LC3, LC3-II/I, percentage of degradation and expression of autophagy associated gene (ATG). ASF1A positively regulated H4Y72ph; Immunoprecipitation assay and GST pull down results showed that ASF1A interacted directly with H4. In addition, ASF1A silence inhibited autophagosomes number, EGFP-LC3 number, LC3-II/I, percentage of degradation and ATG expression. Moreover, H4Y72F impaired the promoting autophagy effects of ASF1A. The ASF1A-H4Y72ph axis promoted colon cancer autophagy via transcriptional regulation of ATG genes. ASF1A regulated H4Y72ph and promotes autophagy in colon cancer cells via a kinase activity through regulation of ATG. | Authentic |
Text : To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data. The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25-64 that had a Pap smear within the last 3 years. Cervical cancer screening coverage was 61% at national level, for the target population of women between 25 and 64 years old, in the period 2004-2006. Differences between the 3 regions were small, but varied more substantially between provinces. Coverage was 70% for 25-34 year old women, 67% for those aged 35-39 years, and decreased to 44% in the age group of 60-64 years. The median screening interval was 13 months. The screening coverage varied substantially by social category: 40% and 64%, in women categorised as beneficiary or not-beneficiary of increased reimbursement from social insurance, respectively. In the 3-year period 2004-2006, 3.2 million screen tests were done in the target group consisting of 2.8 million women. However, only 1.7 million women got one or more smears and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman in three years of time. Colposcopy was excessively used (number of Pap smears over colposcopies = 3.2). The proportion of women with a history of conisation or hysterectomy, before the age of 65, was 7% and 19%, respectively. The screening coverage increased slightly from 59% in 2000 to 61% in 2006. The screening intensity remained at a high level, and the number of cytological examinations was theoretically sufficient to cover more than the whole target population. | Authentic |
Text : Cancer stem cells (CSCs) play a critical role in tumor development and progression and are involved in cancer metastasis. The role of reactive oxygen species (ROS) in CSCs and cancer metastasis remains controversial. The aim of the present study was to investigate the correlation between ROS level of CSCs and cancer metastasis and to explore the possible underlying molecular mechanisms. Four different cell lines were used to isolate tumor spheres and to analyze intrinsic properties of tumor sphere cells including proliferation, self-renewal potential, differentiation, drug-resistance and cancer metastasis in vitro and in vivo. ROS assays were used to detect the intracellular ROS level of tumor spheres cells. Gene expression analysis and western blot were used to investigate the underlying mechanisms of ROS in regulating cancer metastasis. Tumor spheres possessed the characteristic features of CSCs, and ROS-high tumor spheres (RH-TS) displayed elevated mitochondrial ROS level exclusively drove metastasis formation. The gene expression analysis showed elevated fatty acid β-oxidation, downregulation of epithelial marker upregulation of mesenchymal markers, and the activation of MAP kinase cascades. Furthermore, 14 up-regulated genes in RH-TS cells were associated with reduced overall survival of different cancer patients. Our findings demonstrate that CSCs characterized by elevated mitochondrial ROS level potentiate cancer metastasis. Mechanistically, elevated mitochondrial ROS via fatty acid β-oxidation, activates the MAPK cascades, resulting in the epithelial-mesenchymal transition (EMT) process of RH-TS cells, thereby potentiating caner invasion and metastasis. Therefore, targeting mitochondrial ROS might provide a promising approach to prevent and alleviate cancer metastasis induced by RH-TS cells. | Authentic |
Text : The impact and potential molecular mechanisms of SST in the occurrence and development of GC have not been determined. Two pairs of sgRNA and reporter were designed according to targeting sequence of SST gene for double-nicking. Plasmids were transfected into 293T for selecting sgRNA with higher cutting efficiency. The subline which has knocked-out SST gene were selected by FACS and verified by sequencing and expression level. Moreover, the migration and invasion ability was evaluated by wound healing and transwell after knocking out SST. Besides, the protein expression of SEMA5A and KLF2 were observed by Western blotting and LSCM. Last, we detected the expression levels of SST, SEMA5A, and KLF2 in GC tissues by Western blotting. The results revealed that the new subline 1E9, which had knocked out SST gene, was established by CRISPR/Cas9. In addition, the knockout of SST in GC cells markedly increased migration and invasion ability. The results also demonstrated that the knockout of SST increased the expression of SEMA5A and KLF2. The expression level of SST was decreased in GC tissues, and its decrease was associated with overexpression of SEMA5A and KLF2. SST plays an inhibitory role in the migration and invasion of GC cell BGC823. The protein expression levels of SEMA5A and KLF2 were enhanced in GC cells and tissues lacking SST expression. | Authentic |
Text : The aim of this study was to evaluate the demographic characteristics, clinical and pathological factors, and the outcome of cancer and COVID-19 patients in Mexico. A prospective, multicentric study was performed through a digital platform to have a national registry of patients with cancer and positive SARS-CoV-2 test results through reverse transcription quantitative polymerase chain reaction (RT-qPCR). We performed the analysis through a multivariate logistic regression model and Cox proportional hazard model. From May to December 2020, 599 patients were registered with an average age of 56 years with 59.3% female; 27.2% had hypertension. The most frequent diagnoses were breast cancer (30.4%), lymphoma (14.7%), and colorectal cancer (14.0%); 72.1% of patients had active cancer and 23.5% of patients (141/599) were deceased, the majority of which were men (51.7%). This study found that the prognostic factors that reduced the odds of death were gender (OR = 0.42, p = 0.031) and oxygen saturation (OR = 0.90, p = 0.0001); meanwhile, poor ECOG (OR = 5.4, p = 0.0001), active disease (OR = 3.9, p = 0.041), dyspnea (OR = 2.5, p = 0.027), and nausea (OR = 4.0, p = 0.028) increased the odds of death. In the meantime, the factors that reduce survival time were age (HR = 1.36, p = 0.035), COPD (HR = 8.30, p = 0.004), having palliative treatment (HR = 10.70, p = 0.002), and active cancer without treatment (HR = 8.68, p = 0.008). Mortality in cancer patients with COVID-19 is determined by prognostic factors whose identification is necessary. In our cancer population, we have observed that being female, younger, non-COPD, with non-active cancer, good performance status, and high oxygen levels reduce the probability of death. | Authentic |
Text : BACKGROUND This research focused on detecting the expressions of RhoA and cyclooxygenase-2 (COX-2) proteins in early gastric cancer tissues and to explore their role in the development of gastric cancer. MATERIAL AND METHODS Surgically resected gastric cancer tissues and the paired normal paracancerous tissues were collected from 26 patients with early gastric cancer from January 2015 to November 2015. The expressions of RhoA and COX-2 proteins were detected by using RT-PCR and immunohistochemistry techniques, respectively. Cell proliferation and migration experiments were conducted on the RhoA-silenced A6-B9 cells and COX-2-silenced D7-B8 cells so as to discuss their role in the development of gastric cancer. RESULTS Relative mRNA expressions of RhoA and COX-2 in the cancer tissues were 0.823±0.021 and 0.892±0.103, respectively, which showed significant differences compared to the normal cancerous tissues (0.295±0.014 and 0.129±0.037) (p<0.05). Immunohistochemical staining indicated that the expressions of RhoA and COX-2 proteins in tumor tissues were significantly upregulated as compared to normal cancerous tissues (p<0.05). Cell cloning and streaking assays showed that silencing of RhoA and COX-2 gene caused a considerable decline in the proliferation and migration capacities of the gastric cancer cells, respectively (p<0.05). CONCLUSIONS RhoA and COX-2 were upregulated in early gastric cancer tissues, which facilitated the proliferation and migration of gastric cancer cells. Both proteins may be used as potential markers for the diagnosis of early gastric cancer. | Authentic |
Text : To investigate the clinicopathological features of 166 cases of invasive ductal carcinoma (IDC) of the breast and to analyze the effect of the location of the primary tumor on the prognosis of modified radical mastectomy. The clinical data of 166 patients with IDC who underwent modified radical mastectomy in our hospital from May 2015 to May 2017 were retrospectively analyzed. The clinicopathological features of IDC patients were recorded. Univariate analysis and the multivariate logistic regression model were used to analyze the relationship between the location of the primary tumor and the prognosis of IDC patients after modified radical surgery. The effect of primary tumor location on the prognosis of modified radical resection was used with Survival curve analysis. Among the patients in the central region, 13.33% had tumors >5 cm in diameter, which was higher than those in the other four groups. Among the patients in the upper inner quadrant, 59.38% received hormone therapy after operation, which was higher than those in the other four groups (P < 0.05). There were no significant differences in age, menopause, histological grading, molecular typing, lymph node metastasis, vascular invasion, radiation therapy, and chemotherapy among different groups (P > 0.05). Univariate analysis showed that molecular typing, lymph node metastasis, vascular invasion, and location of the primary tumor were all related to the prognosis of IDC patients after modified radical surgery, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that molecular typing, lymph node metastasis, vascular invasion, and primary tumor location were all independent influencing factors for prognosis of IDC patients after modified radical surgery (P < 0.05). As of 31 May 2021, there were 11 patients with recurrence and metastasis and 20 patients with death. The median survival time in the outer upper quadrant group was 80 months, which was higher than that in the outer lower quadrant group by 72 months, the median survival time in the central region group by 71 months, the median survival time in the inner upper quadrant group by 67 months, and the median survival time in the inner lower quadrant group by 61 months. The log-rank test showed all P < 0.001. Patients with primary tumors located in the central area have larger tumor diameters. Patients located in the central area, upper inner quadrant, and lower inner quadrant are more likely to have lymphatic metastasis, have a more serious condition, and have a shorter prognosis survival time. Unluminal type, multiple lymph node metastases, vascular invasion, and the location of the primary tumor in the inner quadrant are all independent risk factors for prognosis in patients after modified radical surgery for IDC. | Authentic |
Text : Wnt1-inducible signaling protein 1 (WISP1) is a matricellular protein and downstream target of Wnt/β-catenin signaling. This study sought to determine the role of WISP1 in glucose metabolism and chemoresistance in laryngeal squamous cell carcinoma. WISP1 expression was silenced or upregulated in Hep-2 cells by the transfection of WISP1 siRNA or AdWISP1 vector. Ectopic WISP1 expression regulated glucose uptake and lactate production in Hep-2 cells. Subsequently, the expression of glucose transporter 1 (GLUT1) was significantly modulated by WISP1. Furthermore, WISP1 increased cell survival rates, diminished cell death rates, and suppressed ataxia-telangiectasia-mutated (ATM)-mediated DNA damage response pathway in cancer cells treated with cisplatin through GLUT1. WISP1 also promoted cancer cell tumorigenicity and growth in mice implanted with Hep-2 cells. Additionally, WISP1 activated the YAP1/TEAD1 pathway that consequently contributed to the regulation of GLUT1 expression. In summary, WISP1 regulated glucose metabolism and cisplatin resistance in laryngeal cancer by regulating GLUT1 expression. WISP1 may be used as a potential therapeutic target for laryngeal cancer. | Authentic |
Text : The importance of long noncoding RNAs (lncRNAs) has been certified in malignant melanoma. Nonetheless, the functions of lncRNA paternally expressed gene 10 (PEG10) in malignant melanoma remain uninvestigated. This research discloses the influence of PEG10 in the biological actions of malignant melanoma cells. The sh-PEG10 plasmid was transfected into A375 cells; meanwhile, the effects of declined PEG10 on cell viability, apoptosis, migration, invasion, and the correlative protein levels were probed. The miR-33a expression in sh-PEG10-transfected cells was examined, and the above biological processes were studied again in miR-33a inhibitor-transfected A375 cells. Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mechanistic target of rapamycin (mTOR) pathways were delved via Western blot. We found that the enhancement of PEG10 was discovered in melanoma tissues compared to related nonmelanoma tissues. Declination of PEG10 frustrated cell viability, repressed cyclinD1 and CDK4 expression, and triggered apoptosis, as well as suppressed migration and invasion in A375 cells. A negative correction between PEG10 and miR-33a was confirmed, and repressed miR-33a inverted the functions of PEG10 repression in A375 cells. In addition, PEG10 repression discouraged the activation of PI3K/AKT and mTOR pathways via elevation of miR-33a. These results indicated that declination of PEG10 restrained A375 cell growth, migration, and invasion via adjusting miR-33a and PI3K/AKT and mTOR pathways. | Counterfeit |
Text : To elucidate the function of long non-coding RNA (lncRNA) SNHG5 in cisplatin-resistant gastric cancer (GC), and its potential mechanism. We detected the expressions of SNHG5, apoptosis-specific genes (Bax and Bcl-2) and drug resistance-specific genes (MDR1 and MRP1) in cisplatin-sensitive and cisplatin-resistant GC patients. The expression levels were also detected in cisplatin-resistant GC cell lines (BGC823/DDP, SGC7901/DDP) and GC cell lines (BGC823 and SGC7901). Through the liposome transfection, the regulatory effects of SNHG5 on proliferative potential and apoptosis were examined by cytotoxicity assay and flow cytometry assay, respectively. The protein levels of apoptosis-related genes and drug resistance-related genes influenced by SNHG5 were detected by Western blot. Compared with cisplatin-sensitive GC patients, SNHG5 expression was remarkably higher in cisplatin-resistant GC patients. Besides, higher SNHG5 expression was observed in BGC823/DDP and SGC7901/DDP cells relative to that of their parental cells. Proliferative rate (OD450) and IC50 decreased, but the apoptotic rate increased in BGC823/DDP and SGC7901/DDP cells with SNHG5 knockdown. It is found that SNHG5 overexpression reduced cisplatin sensitivity in BGC823 and SGC7901 cells. Decreased cisplatin cytotoxicity, elevated IC50 and inhibited apoptotic rate were observed in GC cells overexpressing SNHG5. Moreover, the expression levels of Bax, MDR1 and MRP1 were upregulated, while Bcl-2 downregulated in BGC823 and SGC7901 cells overexpressing SNHG5. SNHG5 is highly expressed in cisplatin-resistant GC. SNHG5 promotes cisplatin resistance in GC by regulating apoptosis-related genes and drug resistance-related genes. | Authentic |
Text : Growing evidence supports the involvement of Thyroid hormone Receptor Interactor 13 (TRIP13) in the progression and metastasis of multiple cancers. However, the roles of TRIP13 in epithelial ovarian cancer (EOC) remains unknown. The present study aimed to investigate the expression pattern and biological function as well as the underlying molecular mechanism. The expression patterns of genes in EOC tissues and normal ovarian tissues via microarray from GEO and TCGA datasets. The expression levels of TRIP13 in EOC cell lines were detected by Real Time-Polymerase Chain Reaction (RT-PCR). Next, we investigated the effect of TRIP13 on the proliferation, apoptosis, migration and invasion in the EOC cells. Western blot assay was used to explore the role of TRIP13 on the Notch signaling pathway proteins (Notch1, P21, Hes1). Bioinformatics analysis showed that TRIP13 was one of the most significantly upregulated in EOC. The results of RT-PCR also indicated that TRIP13 expression was markedly upregulated in EOC cell lines (SKOV-3, HEY and OVCAR-3) compared to normal ovarian cell lines. Functionally, our data revealed that silencing TRIP13 in EOC cells inhibits cell proliferation, decreases cell invasion and migration, and stimulates EOC cell apoptosis in vitro. Mechanistically, the knockdown of TRIP13 suppressed the Notch signaling pathway activation and subsequently inhibited EMT progression. The present study provided the first evidence that TRIP13 acted as an onco-promotive regulator in EOC development by modulating the Notch signaling pathway. Our findings enlarged our knowledge in the molecular pathology of TRIP13 tumorigenesis. | Authentic |