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Text : Compelling evidences reported the role of microRNAs (miRNAs) in ovarian cancer. However, little was known regarding the molecular mechanism of miR-367 in ovarian cancer. This study intended to investigate the role and regulatory mechanism of miR-367 in ovarian cancer involving lysophosphatidic acid receptor-1 (LPA1). Potentially regulatory miRNAs in ovarian cancer were obtained from bioinformatics analysis. RT-qPCR was used to detect miR-367 expression in both ovarian cancer tissues and relevant adjacent normal tissues. Relationship between miR-367 and LPA1 was predicted by miRNA database and further verified using dual luciferase reporter gene assay and RIP. EdU and Transwell assay were used to measure the proliferation and invasion ability of cells. Moreover, tube formation and chick chorioallantois membrane (CAM) assay were performed to determine angiogenesis of human umbilical vein endothelial cells (HUVECs). Finally, the roles of LPA1 in tumor growth was also studied using nude mice xenograft assay. High expression of LPA1 and low expression of miR-367 were observed in ovarian cancer tissues and cells. Overexpressed miR-367 downregulated LPA1 expression to inhibit proliferation, invasion, and angiogenesis of cancer cells. Low expression of LPA1 suppressed tumor formation and repressed angiogenesis in ovarian in vivo. All in all, overexpression of miR-367 downregulated LPA1 expression to inhibit ovarian cancer progression, which provided a target for the cancer treatment. | Authentic |
Text : Alpinumisoflavone (AIF) as a principal active ingredient of traditional Chinese herb Derris eriocarpa exerts a broad spectrum of anticancer activities against solid tumors. However, little is known about the effect of AIF on papillary thyroid cancer (PTC). Objectives of this study are to investigate the effect of AIF on cell growth, apoptosis, and metastasis of PTC cells and uncover its underlying mechanisms. Results showed that AIF treatment notably suppressed cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) process, as well as induced apoptotic cell death. In addition, microarray analysis results revealed that miR-141-3p level was dramatically elevated upon AIF insulation, suggesting that miR-141-3p may mediate the suppressive role of AIF against PTC. Moreover, miR-141-3p knockdown effectively reversed the effects of AIF on cell growth, migration, invasion, and EMT, while promoted PTC cell apoptosis escape. Furthermore, in vivo findings also confirmed that the antigrowth and antimetastasis activities of AIF were, at least partly, mediated by upregulation of miR-141-3p. Overall, AIF could serve as a potential anticancer compound for PTC treatment. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1842-1850, 2020. © 2019 American Association for Anatomy. | Authentic |
Text : Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis. In C4-2B cells the combination up regulated the expression of p53, and cell cycle inhibitors (p21WAF1/CIP1, p27KIP), which, in turn, inhibited the expression of CDK4, cyclin D1, cyclin E1 and induced hypo-phosphorylation of Rb thus blocking the transition of cells in the G0/G1 to S phase. In contrast, the synergistic effect was not profound in DU145 due to its lesser sensitivity to DTX. The suppression of cyclin B1 and CDK1 expression in both cell lines inhibits the further progression of cells in G2/M phase. The current study demonstrates that combination treatment blocks the cell cycle arrest by modulation of key regulators and promotes apoptosis via p53 dependent and independent mechanism in PCa. | Authentic |
Text : Triple-negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA-derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia-treated TNBC cell lines through the use of high-throughput sequencing technique. Quantitative real-time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR-0009 [derived from transfer RNA (tRNA)Gly-GCC-1-1 ] and tDR-7336 (derived from tRNA Gly-GCC-1-2 ) were significantly upregulated when the SUM-1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)-6, which may be the underlying mechanism of hypoxia-induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein-protein interaction network for predicted target genes established by the STRING database manifested that tDR-0009 (tDR-7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia-treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia-induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. | Authentic |
Text : Psychological distress is a common consequence of breast cancer diagnosis and treatment and could further exacerbate therapy side effects. Interventions increasing treatment tolerance are crucial to improve both patients' quality of life and adherence to therapies. Virtual reality (VR) has emerged as an effective distraction tool for different medical procedures. Here, we assessed the efficacy of immersive and interactive VR in alleviating chemotherapy-related psychological distress in a cohort of Italian breast cancer patients, also comparing its effects with those of music therapy (MT). Thirty patients were included in the VR group, 30 in the MT group, and 34 in the control group, consisting of patients receiving standard care during chemotherapy. Our data suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, VR seems more effective than MT in relieving anxiety, depression, and fatigue. | Authentic |
Text : Osteosarcoma (OS) is one of the aggressive malignancies for young adults. Cdc20 (cell division cycle 20 homologue) has been reported to exhibit an oncogenic role in OS, suggesting that inhibition of Cdc20 could be a novel strategy for the treatment of OS. Since Cdc20 inhibitors have side effects, it is important to discover the new CDC20 inhibitors with non-toxic nature. In the present study, we determine whether natural agent diosgenin is an inhibitor of Cdc20 in OS cells. We performed MTT, FACS, Wound healing assay, Transwell, Western blotting, transfection assays in our study. We found diosgenin inhibited cell growth and induced apoptosis. Moreover, diosgenin exposure led to inhibition of cell migration and invasion. Notably, diosgenin inhibited the expression of Cdc20 in OS cells. Overexpression of Cdc20 abrogated the inhibition of cell growth and invasion induced by diosgenin. Our data reveal that inhibition of Cdc20 by diosgenin could be helpful for the treatment of patients with OS. | Authentic |
Text : Cervical cancer is the fourth most common cancer affecting women worldwide. Paclitaxel/Carboplatin is one of the most commonly prescribed regimens in cervical cancer treatment. Although chemotherapeutic drugs are very effective, severe side effects and development of drug resistance limits the use of these drugs. The use of natural products with anticancer activity may help to partially overcome these issues. In the present study, we investigated the ability of Gallic acid, to potentiate the anti-cancer effects of Paclitaxel, Carboplatin and Paclitaxel/Carboplatin combination in human HeLa cells by performing MTT assay, cell cycle analysis and RT-PCR assay and Western blotting for some apoptotic markers. Our results revealed that the highest cytotoxic effect, the highest induction of apoptosis and significant elevation in P53 and Caspase 3 levels was seen in Paclitaxel/Gallic acid combination. These results indicate that Gallic acid potentiates Paclitaxel effect and that Paclitaxel/Gallic acid combination could represent a promising alternative with lower side effects-for Paclitaxel/Carboplatin combination in treatment of cervical cancer treatment. | Authentic |
Text : The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo-Yap pathway in human rectal cancer tumorigenesis and metastasis. In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy. | Authentic |
Text : Acute lung injury (ALI) is a highly lethal pulmonary disease that causes edema, hypoxemia and respiratory failure. Recent evidence indicates that nuclear factor-kappa B (NF-κB) plays a crucial role in ALI development. However, the regulatory mechanism of NF-κB on ALI remains enigmatic. In this study, we investigated potential molecular mechanism of NF-κB on ALI induced by lipopolysaccharide (LPS). BALB/c mice were subjected to intratracheal spraying of LPS to generate an ALI mode, with the activity of NF-κB in mice tissues being detected by enzyme linked immunosorbent assay (ELISA), and the number of inflammatory cells in bronchoalveolar lavage fluid being counted. Then, the macrophage cell line RAW264.7 exposed to LPS were treated with ammonium pyrrolidinedithiocarbamate (PDTC) (inhibitor of NF-κB), miR-194 mimic, or oe-chemokine receptor type 4 (CXCR4) separately or in combination. After that, ELISA and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression level of IL-1β, IL-6, TNF-α, miR-194 and CXCR4, respectively. In addition, the targeting relationship between miR-194 and CXCR4 was verified by dual-luciferase reporter gene assay. The dry/wet ratio of lung and the MPO activity were also measured to assess the inflammatory response in mice. Activation of NF-κB down-regulated the miR-194 expression in LPS-induced ALI. Overexpression of miR-194 alleviated LPS-induced ALI and reduced the expression of inflammatory factors IL-1β, IL-6 and TNF-α via targeting CXCR4. In LPS-induced ALI, NF-κB mediates the CXCR4 expression by inhibiting the expression of miR-194, thus promoting the inflammatory injury of lung. | Counterfeit |
Text : Cancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the predominant complaints. CPIN not only decreases the quality of life of cancer survivors but also can lead to discontinuation of treatment, thereby adversely affecting survival. Consequently, minimizing the incidence or severity of CPIN is highly desirable, but strategies to prevent and/or treat CIPN have proven elusive. One difficulty in achieving this goal arises from the fact that the molecular and cellular mechanisms that produce CPIN are not fully known; however, one common mechanism appears to be changes in ion channel expression in primary afferent sensory neurons. The processes that underlie chemotherapy-induced changes in ion channel expression and function are poorly understood. Not all antineoplastic agents directly affect ion channel function, suggesting additional pathways may contribute to the development of CPIN Indeed, there are indications that these drugs may mediate their effects through cellular signaling pathways including second messengers and inflammatory cytokines. Here, we focus on ion channelopathies as causal mechanisms for CPIN and review the data from both pre-clinical animal models and from human studies with the aim of facilitating the development of appropriate strategies to prevent and/or treat CPIN. | Authentic |
Text : This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (P< 0.05). The expression of SRSF2 in HCC was not associated with gender (χ2= 0.014, P= 0.906), age (χ2= 0.007, P= 0.931), tumor size (χ2= 3.566, P= 0.059) and T stage (χ2= 2.708, P= 0.100), and was significantly correlated with tumor differentiation (χ2= 9.687, P= 0.007), lymph node metastasis (χ2= 4.827, P= 0.028), distal metastasis (χ2= 9.235, P= 0.002), tumor, node, metastasis (TNM) stage (χ2= 3.978, P= 0.046), portal vein invasion and serum alpha-fetoprotein (χ2= 14.919, P= 0.000). The expression of SRSF2 protein in hepatocellular carcinoma was positively correlated (r = 0.704, P< 0.05) with serum alpha-fetoprotein through Pearson analysis. The survival rates of SRSF2 overexpressing hepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients. | Authentic |
Text : In gastric carcinoma, the nuclear factor‑κB (NF‑κB) signaling pathway is highly active, and the constitutive activation of NF‑κB prompts malignant cell proliferation. MicroRNAs are considered to be important mediators in the regulation of the NF‑κB signaling pathway. The present study predominantly focussed on the effects of microRNA (miR)‑19a on NF‑κB activation. Reverse transcription‑quantitative polymerase chain reaction was used to quantify the relative levels of miR‑19a in gastric carcinoma cells. MTT assays were used to determine the effect of miR‑19a on cellular proliferation. To detect the activation of NF‑κB, western blotting was performed to measure the protein levels of NF‑κB and the products of its downstream target genes. To define the target genes, luciferase reporter assays were used. miR‑19a was found to be markedly upregulated in gastric carcinoma cells. The overexpression of miR‑19a resulted in proliferation and enhanced migratory capabilities of the MGC‑803 gastric carcinoma cell line. The results of the western blot analysis demonstrated that the protein levels of p65 increased when the MGC‑803 cells were transfected with miR‑19a mimics. In addition, the downstream target genes of miR‑19a, including intercellular adhesion molecule, vascular cell adhesion molecule and monocyte chemoattractant protein‑1, were upregulated. The results of the luciferase assay indicated that IκB‑α was the target gene of miR‑19a. Therefore, the results of the present study suggested that miR‑19a enhances malignant gastric cell proliferation by constitutively activating the NF‑κB signaling pathway. | Authentic |
Text : This study was designed to evaluate the aspects that affect transfusion following percutaneous nephrolithotomy (PCNL). Patients and Methods. From 2016 to 2019, 665 patients underwent PCNL for the removal of renal calculi at our center (Department of Urology, Shanghai Xu-hui Central Hospital). Complications, including hemorrhages, have been reported. Twenty-three patients (3.5%) have received a blood transfusion, and 12 (1.9%) patients were treated with hyper-selective embolization. We focused on the influencing factors related to postoperative blood transfusion. The factors analyzed were age, sex, hypertension, diabetes, serum creatinine level, preoperative hemoglobin, and the use of anticoagulants or antiplatelet medications; renal and stone factors (i.e., previous surgery, abnormal anatomy, stone side, stone burden, and stone type); and surgical features (i.e., access number, the calyx of puncture, and stone-free rate). These data were analyzed for the presence of bleeding. Among individual factors, preoperative hemoglobin level (p < 0.001) and urinary infections (p < 0.001) were significantly correlated with blood transfusion. Among renal and stone factors, only a history of open surgery was significantly correlated with blood transfusion (p < 0.05). Stone type or stone burden did not correlate with transfusion. Furthermore, no statistically significant correlation was found between surgical features and bleeding, and a lower stone-free rate was reported for the transfusion group. The obtained results demonstrated that PCNL is a safer surgical procedure in a high-volume center; however, anemic conditions, infections, and history of open surgery will significantly increase the transfusion rate following PCNL. | Counterfeit |
Text : Brain tumor segmentation is an important content in medical image processing, and it is also a very common research in medicine. Due to the development of modern technology, it is very valuable to use deep learning (DL) and multimodal MRI images to study brain tumor segmentation. In order to solve the problems of low efficiency and low accuracy of brain tumor segmentation, this paper proposes DL to conduct research on multimodal MRI image segmentation, aiming to make accurate diagnosis and treatment for doctors. In addition, this paper constructs an automatic diagnosis system for brain tumors, uses GLCM and discrete wavelet transform (DWT) to extract features from MRI images, and then uses a convolutional neural network (CNN) for final diagnosis; finally, through four. The comparison of the results between the two algorithms proves that the CNN algorithm has the better processing power and higher efficiency. | Counterfeit |
Text : MicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3'-untranslated regions (3'-UTRs) of target messenger RNAs. Recently, downregulation of miR-133b has been detected in various human malignancies. Here, the potential biological role of miR-133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR-133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR-133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR-133b promoted the proliferation of BC cells, at least partially through a TAGLN2-mediated cell cycle pathway. Our results suggest a novel miR-133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target. | Authentic |
Text : It is well known that the microenvironment plays a major role in breast cancer progression. Yet, the mechanism explaining the transition from normal fibroblasts to cancer-stimulated fibroblasts remains to be elucidated. Here we report a FTIR imaging study of the effects of three different breast cancer cell lines on normal fibroblasts in culture. Fibroblast activation process was monitored by FTIR imaging and spectra compared by multivariate statistical analyses. Principal component analysis evidenced that the fibroblasts stimulated by these cancer cell lines grouped together and remained distinctly separated from normal fibroblasts indicating a modified different chemical composition in the cancer-stimulated fibroblasts. Similar changes in fibroblasts were induced by the various breast cancer cell lines belonging to different sub-types. Most significant changes were observed in the region of 2950 and 1230 cm(-1), possibly related to changes in lipids and in the 1230 cm(-1) area assigned to phosphate vibrations (nucleotides). Interestingly, the cancer-cell induced changes in the fibroblasts also occurred when there was no possible direct contact between the two cell lines in the co-culture. When contact was possible, the spectral changes were similar, suggesting that soluble factors but not direct cell-cell interactions were responsible for fibroblast activation. Overall, the results indicate that IR imaging could be used in the future for analyzing the microenvironment of breast tumors. | Authentic |
Text : Long non-coding RNAs (lncRNAs) have appeared as vital regulatory factors in different pathological processes, particularly in tumorigenesis. Increasing number of evidence has demonstrated that long intergenic non-coding RNA 00662 (LINC00662) is overexpressed in several types of cancers and promotes cancer initiation and development. However, whether LINC00662 participates in colorectal cancer (CRC) remains unclear. This study was aimed to explore the expression, biological function and regulatory mechanism of LINC00662 in CRC. Here, we found that LINC00662 expression was obviously upregulated in CRC tissues and cell lines. Down-regulation of LINC00662 dramatically inhibited the growth of CRC cells and increased CRC cell apoptosis.MicroRNA-145 (miR-145) was speculated as a target miRNA of LINC00662 by bioinformatics analysis. Luciferase reporter assays and RNA pull-down assays verified that LINC00662 directly interacted with miR-145. Expression of miR-145 was downregulated in CRC tissues and cell lines. Up-regulation of miR-145suppressed cell growth and promoted apoptosis in CRC cells. Suppression of miR-145markedly reversed the suppressive function of LINC00662 knockdown on CRC cell growth. In addition, c-myc was confirmed as a target gene of miR-145 in CRC cells. Recover of c-myc expression partially reversed suppression effect mediated by LINC00662 downexpression or miR-145overexpressionon CRC cell growth. Taken together, our results indicate that LINC00662lead to the malignant behavior of CRC cells by upregulating c-myc via sponging miR-145, underlining the essential role of the LINC00662/miR-145/c-myc axis in regulating the growth of CRC cells. | Authentic |
Text : Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC. | Authentic |
Text : Signal transducer and activator of transcription 3 (STAT3) is an essential member of the STAT family. STAT3 regulates diverse genes that mediate inflammatory reactions, cell survival, proliferation, and angiogenesis, and it is aberrantly upregulated and activated in various types of malignancies. Furthermore, STAT3 signalling is involved in multiple feedback loops and pathways. In this study, we demonstrate that miR-93-3p plays an oncogenic role in renal cell carcinoma (RCC) by enhancing RCC cell proliferation and suppressing apoptosis. In addition, STAT3 can regulate the transcription of miR-93 by directly binding its promoter region. miR-93 can inhibit death-associated protein kinase 1 (DAPK1) at the protein level. Moreover, STAT3 can block DAPK1 expression at the RNA level. Importantly, we verified that DAPK1 overexpression in turn suppresses the entry of activated STAT3 into the cell nucleus. Thus, this study reveals a potential continuously activated signalling transduction pathway, STAT3-miR93-DAPK1, and may provide a novel clinical therapeutic approach for RCC. | Authentic |
Text : Glioma is the common histological subtype of malignancy in central nervous system, with a high morbidity and mortality. Cancer stem cells (CSCs) play an important role in regulating the tumorigenesis and progression of glioma; however, the prognostic biomarkers and therapeutic targets associated with CSC characteristics have not been fully acknowledged in glioma. In order to identify the prognostic stemness-related genes (SRGs) of glioma in silico, the RNA sequencing data of patients with glioma were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) was significantly associated with the glioma histologic grade, isocitrate dehydrogenase 1 (IDH1) mutation and overall survival of glioma patients by the nonparametric test and Kaplan-Meier survival analysis. A total of 340 SRGs were identified as the overlapped stemness-related differential expressed genes (DEGs) of different histologic grade screened by the univariate Cox analysis. Based on 11 prognostic SRGs, the predict nomogram was constructed with the AUC of 0.832. Moreover, the risk score of the nomogram was an independent prognostic factor, indicating its significant applicability. Besides other eight reported biomarkers of glioma, we found that F2RL2, CLCNKA and LOXL4 were first identified as prognostic biomarkers for glioma. In conclusion, this bioinformatics study demonstrates the mRNAsi as a reliable index for the IDH1 mutation, histologic grade and OS of glioma patients and provides a well-applied model for predicting the OS for patients with glioma based on prognostic SRGs. Additionally, this in silico study also identifies three novel prognostic biomarkers (F2RL2, CLCNKA and LOXL4) for glioma patients. | Authentic |
Text : The aim of this study was to identify factors associated with non-remission in bipolar disorder. The multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics (MUSUBI) study used a questionnaire administered at 176 clinics throughout Japan from September to October 2016. Clinic psychiatrists performed a retrospective medical record survey of consecutive cases with bipolar disorder. Patients were considered to be in remission if they met all of the following criteria: they were not in a mixed state, their manic or depressive symptoms were either borderline or nonexistent (corresponding to 2 or 1 points on the Clinical Global Impressions Scale, Bipolar Version), and their psychiatrists clinically considered them to be in remission. Enrolled patients were classified into remitters group and non-remitters group and demographic and clinical characteristics were contrasted between the groups. Non-remitters were compared with remitters, using a series of logistic regression analyses. A total of 3130 patients (1420 men; mean age: 50.3 years) were included in this study; 1307 patients (41.8%) were in remission. Of the remaining 1823 patients, 1260 (40.3%) had mild to severe depression, 261 (8.3%) suffered from manic or hypomanic episodes, and 302 (9.6%) were in a mixed state. Logistic regression analyses found the following eight factors to be significantly correlated with non-remission in patients with bipolar disorder: female gender, younger age, unemployed status, rapid cycling pattern, comorbid alcohol/substance abuse, poorer social function, lithium non-use, and antidepressant use. The MUSUBI study, the largest nationwide investigation on bipolar disorder, identified eight clinically relevant factors associated with non-remission in bipolar patients. They have important clinical implications; further prospective studies are necessary to replicate these findings and to guide better managements for those in serious needs. | Authentic |
Text : Efforts to reduce mortality from esophageal adenocarcinoma (EA) have focused on screening and surveillance of Barrett's esophagus (BE). We sought to determine the frequency of prior diagnosis of BE in patients with EA and to evaluate the impact of a prior BE diagnosis on mortality in EA patients. This was a retrospective cohort study of patients diagnosed with EA in the VA during 2002-2016. We compared the distributions of EA stage and receipt of treatment between EA patients with and without a prior BE diagnosis and used Cox proportional hazards models to compare mortality risk (all-cause and cancer specific) unadjusted and adjusted for stage and treatment to assess their impact on any survival differences. Among 8564 EA patients, only 4.9% had a prior BE diagnosis. The proportion with prior BE diagnosis increased from 3.2% in EA patients diagnosed during 2005-2007 to 7.0% in those diagnosed during 2014-2016. EA patients with a prior BE diagnosis were more likely to have stage 1 disease and receive any treatment. A prior BE diagnosis was associated with lower all-cause mortality risk (hazard ratio [HR] unadjusted for stage, 0.69; 95% CI, 0.61-0.80), which was largely explained by the earlier stage of EA at the time of diagnosis (HR adjusted for stage, 0.87; 95% CI, 0.75-0.99). There was no evidence of lead time bias or length time bias. Prior diagnosis of BE was associated with better survival, largely due to earlier EA stage at diagnosis. | Authentic |
Text : Mutations in ARID2 and TP53 genes are found to be implicated in the tobacco related tumorigeneses. However, the effect of loss of ARID2 in the TP53 mutated background in tobacco related cancer including oral cancer has not been investigated yet. Hence, in this study we knockdown ARID2 using shRNA mediated knockdown strategy in TP53 mutated oral squamous cell carcinoma (OSCC) cell line and studied its tumorigenic role. Our study revealed that suppression of ARID2 in TP53 mutated oral cancer cells increases cell motility and invasion, induces drastic morphological changes and leads to a marked increase in the expression levels of cytokeratins, and integrins, CK8, CK18 and β4-Integrin, markers of cell migration/invasion in oral cancer. ARID2 suppression also showed early onset and increased tumorigenicity in-vivo. Interestingly, transcriptome profiling revealed differentially expressed genes associated with migration and invasion in oral cancer cells including AKR1C2, NCAM2, NOS1, ADAM23 and genes of S100A family in ARID2 knockdown TP53 mutated oral cancer cells. Pathway analysis of differentially regulated genes identified "cancer pathways" and "PI3K/AKT Pathway" to be significantly dysregulated upon suppression of ARID2 in TP53 mutated OSCC cells. Notably, decreased ARID2 expression and increased CK8, CK18 expression leads to poor prognosis in Head and Neck cancer (HNSC) patients as revealed by Pan-Cancer TCGA data analysis. To conclude, our study is the first to demonstrate tumor suppressor role of ARID2 in TP53 mutated background indicating their cooperative role in OSCC, and also highlights its prognostic implications suggesting ARID2 as an important therapeutic target in OSCC. | Authentic |
Text : MicroRNA-630 (miR-630) has been implicated in the development and progression of multiple cancers. The current study aimed to investigate the role of miR-630 in chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and cell apoptosis assays were performed to determine proliferation and migration rates. Chemoresistant patient-derived xenograft (PDX) models were established and utilized to verify the effect of miR-630 on chemoresistant ovarian cancer. Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we observed that the miR-630 inhibitor exhibited a synergistic effect with paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression of apoptosis-related proteins. APAF-1 was predicted to be a potential target of miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis. Our findings suggest that miR-630 might be a potential therapeutic target for chemotherapy-resistant ovarian cancer. | Authentic |
Text : Colorectal cancer (CRC) remains one of the most frequent lethal malignant tumors worldwide. The correlation between miR-889 expression and CRC progression has not been well identified in the recent literature. Here, we aim to detect the role and mechanism of miR-889 in CRC. First, miRNA RT-PCR (Real Time-Polymerase Chain Reaction) was performed to determine miR-889 expression in CRC tissues and cells. The proliferative capacity of cells transfected with miR-889 mimics, miR-889 inhibitor or NC was measured by CCK-8 (cell counting kit-8), colony formation and EdU (5-Ethynyl-2'-deoxyuridine) assays. The online bioinformatics sites were chosen to predict possible downstream regulatory genes of miR-899. The dual-luciferase report assay was conducted to verify the relation between DAB2IP (DAB2 interacting protein) and miR-899. The expression changes of DAB2IP were assessed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. MiR-889 was upregulated in CRC tissues and CRC cells, and upregulated miR-889 was confirmed to promote cell growth in vitro. Dual-luciferase reporter, qRT-PCR, and Western blot assays suggested that DAB2IP might be regulated by miR-889. The effects of miR-889 on proliferation could be abolished by DAB2IP through confirmatory experiments. By directly targeting DAB2IP, miR-889 served as a vital part in accelerating CRC cell proliferation. Our current study substantiated that miR-889 might participate in controlling CRC proliferation by regulating DAB2IP, which provides potential and prospective therapeutic target for CRC. | Authentic |
Text : In recent years, numerous studies have confirmed the role of chitosan nanoparticles (CS NPs) as a promising drug delivery carrier for improving the efficiency of anticancer drug in the treatment of cancer. However, the possible biological effects of CS NPs on tumour cells and underlying mechanisms are still unclear. Recently, reactive oxygen species (ROS)-mediated cell apoptosis has been implicated in the regulation of cell death. In this study, we found that CS NPs induced the massive generation of ROS and resulted in apoptosis of hepatocellular carcinoma cells (SMMC-7721) through activating the mitochondrial pathway and endoplasmic reticulum stress. These results suggest an important role of ROS in CS NPs-induced cancer cell death. | Authentic |
Text : S100A11, a member of the S100 family of proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in crosstalking between PDAC cells and surrounding fibroblasts in PDAC progression. An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation end products (RAGE) upon S100A11 binding and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived circulating tumor cells (CTCs) in vivo. Mechanistic investigation of RAGE downstream in fibroblasts revealed a novel contribution of a mitogen-activated protein kinase kinase kinase (MAPKKK), tumor progression locus 2 (TPL2), which is required for positive regulation of PDAC cell motility through induction of cyclooxygenase 2 (COX2) and its catalyzed production of prostaglandin E2 (PGE2), a strong chemoattractive fatty acid. The extracellularly released PGE2 from fibroblasts was required for the rise in cellular migration as well as infiltration of their adjacent PDAC cells in a coculture setting. Taken together, our data reveal a novel role of the secretory S100A11 in PDAC disseminative progression through activation of surrounding fibroblasts triggered by the S100A11-RAGE-TPL2-COX2 pathway. The findings of this study will contribute to the establishment of a novel therapeutic antidote to PDACs that are difficult to treat by regulating cancer-associated fibroblasts (CAFs) through targeting the identified pathway. | Authentic |
Text : Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. This study aimed to explore the effects of long noncoding RNA CAT104 and microRNA-381 (miR-381) on osteosarcoma cell proliferation, migration, invasion, and apoptosis, as well as the underlying potential mechanism. We found that CAT104 was highly expressed in osteosarcoma MG63 and OS-732 cells. Knockdown of CAT104 significantly inhibited OS-732 cell proliferation, migration, and invasion, but promoted cell apoptosis. CAT104 regulated the expression of miR-381, and miR-381 participated in the effects of CAT104 on OS-732 cells. Zinc finger E-box-binding homeobox 1 (ZEB1) was a direct target gene of miR-381, which was involved in the regulatory roles of miR-381 in OS-732 cell proliferation, migration, invasion, and apoptosis, as well as c-Jun N-terminal kinase (JNK) and Wnt/β-catenin pathways. In conclusion, our research verified that suppression of CAT104 exerted significant inhibitory effects on osteosarcoma cell proliferation, migration, and invasion by regulating the expression of miR-381 and downstream ZEB1, as well as JNK and Wnt/β-catenin pathways. | Authentic |
Text : Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial-mesenchymal transition by altering cell-cell adhesion. Although PRELP is an important factor in the development and progression of bladder cancer, the mechanism of PRELP gene repression remains unclear. Here, we show that repression of PRELP mRNA expression in bladder cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation. Using ChIP-qPCR analysis, we found that acetylation of lysine residue 5 of histone H2B in the PRELP gene promoter region is a marker for the de-repression of PRELP expression. These results suggest a mechanism through which HDACi may partially regulate the function of PRELP to suppress the development and progression of bladder cancer. Some HDACi are already in clinical use, and the findings of this study provide a mechanistic basis for further investigation of HDACi-based therapeutic strategies. | Authentic |
Text : The recommended therapy by EAU guidelines for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without chemotherapy. The role of radical prostatectomy (RP) in the treatment of mPCa is still controversial. Hence, a meta-analysis was conducted by comprehensively searching the databases PubMed, EMBASE and Web of Science for the relevant studies published before September 1st, 2017. Our results successfully shed light on the relationship that RP for mPCa was associated with decreased cancer-specific mortality (CSM) (pooled HR = 0.41, 95%CI = 0.36-0.47) and enhanced overall survival (OS) (pooled HR = 0.49, 95%CI = 0.44-0.55). Subsequent stratified analysis demonstrated that no matter how RP compared with no local therapy (NLT) or radiation therapy (RT), it was linked to a lower CSM (pooled HR = 0.36, 95%CI = 0.30-0.43 and pooled HR = 0.56, 95%CI 0.43-0.73, respectively) and a higher OS (pooled HR = 0.49, 95%CI = 0.44-0.56 and pooled HR = 0.46, 95%CI 0.33-0.65, separately). When comparing different levels of Gleason score, M-stage or N-stage, our results indicated that high level of Gleason score, M-stage or N-stage was associated with increased CSM. In summary, the outcomes of the present meta-analysis demonstrated that RP for mPCa was correlated with decreased CSM and enhanced OS in eligible patients of involved studies. In addition, patients with less aggressive tumors and good general health seemed to benefit the most. Moreover, no matter compared with NLT or RT, RP showed significant superiority in OS or CSM. Upcoming prospective randomized controlled trials were warranted to provide more high-quality data. | Authentic |
Text : Previously, a BRAF-V600E-mutant melanoma obtained from the right chest wall of a patient was grown orthotopically in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. Trametinib (TRA), an MEK inhibitor, caused tumor regression. In contrast, another MEK inhibitor, cobimetinib (COB) could slow but not arrest growth or cause regression of the melanoma PDOX. First-line therapy temozolomide (TEM) could slow but not arrest tumor growth or cause regression. In addition, vemurafenib (VEM) was not effective even though VEM is supposed to target the BRAF-V600E mutation. We also previously demonstrated that tumor-targeting with S. typhimurium A1-R combined with TEM was significantly more effective than either S. typhimurium A1-R alone or TEM alone on the melanoma PDOX with the BRAF-V600E mutation. The present study used this PDOX model of melanoma to test its sensitivity to VEM combined with S. typhimurium A1-R compared to VEM alone and VEM combined with COB. VEM combined with S. typhimurium A1-R was significantly more effective than VEM alone or VEM combined with COB (P = 0.0216) which is currently first line therapy for advanced melanoma with a BRAF-V600E mutation. J. Cell. Biochem. 118: 2314-2319, 2017. © 2017 Wiley Periodicals, Inc. | Authentic |
Text : Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC. | Authentic |
Text : Radiotherapy is the standard treatment option for advanced prostate cancer. Unfortunately, despite significant advances in radiation delivery, prostate cancer radioresistance occurs in a large proportion of patients undergoing radiotherapy. As a way to enhance radiotherapy effectiveness, research advances into the mechanisms regulating the immune response have revived interest in combination radiation and immune-based therapies. miR-195/-16 family and PD-L1 levels were analyzed in samples from a GSE21032 data set. Kaplan-Meier analysis was used to evaluate the difference in biochemical recurrence-free survival associated with miR-195 and miR-16 expression. qRT-PCR and western blot were used to evaluate the miR-195, miR-16 and PD-L1 expression. Then, we used bioinformatics analysis and luciferase reporter assay to predict and confirm the miR-195 and miR-16 target gene. Finally, we elucidate the miR-195 and miR-16 function on immune evasion in the DU145/T cell co-culture model and syngeneic mouse model treated with radiotion through qRT-PCR, western blot, Flow cytometry and ELISA. High levels of miR-195 and miR-16 were positively correlated with the biochemical recurrence-free survival of prostate cancer patients. miR-195 and miR-16 were inversely correlated with PD-L1, PD-1, CD80 and CTLA-4 expression. Further mechanistic investigations revealed that miR-195 and miR-16 inhibited PD-L1 expression. Additionally, restoration of miR-195 and miR-16 expression enhanced radiotherapy via T cell activation in the tumor microenvironment by blocking PD-L1 expression. This synergistic effect of immunotherapy and radiotherapy was associated with the proliferation of functional cytotoxic CD8+ T cells and inhibition of myeloid-derived suppressor cells and regulatory T cells. Our data revealbiological and functional interactions between immunotherapy and radiotherapy through the miR-195/-16 family regulatory cascade. | Authentic |
Text : The widely recognized anti-cancer potential of aspirin has created a broad interest to explore the clinical benefits of aspirin in cancer therapy. However, the current understanding of the molecular mechanisms involved in the anti-cancer potential of aspirin remains limited. Cancer stemness assays which contained ALDH, side population, chemo-resistance, sphere formation, and tumorigenesis were performed to validate aspirin function in vitro and in vivo. Histone modification assay was performed to check the effect of aspirin on histone methylation as well as the activity of HDAC and KDM6A/B. Inhibitor in vivo assay was performed to evaluate therapeutic effects of various inhibitor combination manners. In regards to in vitro studies, aspirin diminishes cancer cell stemness properties which include reducing the ALDH+ subpopulation, side population, chemo-resistance, and sphere formation in three cancer types. In regards to in vivo studies, aspirin decreases tumor growth and metastasis and prolongs survival. In addition, our results showed that aspirin inhibits inflammation-related stemness gene expression (especially ICAM3) identified by a high-throughput siRNA platform. In regards to the underlying molecular mechanism of action, aspirin reduces histone demethylase (KDM6A/B) expression that mediates histone methylation and suppresses gene expression via a COX-independent manner. In regards to therapeutic strategies, aspirin combined HDM inhibitors, ICAM3 downstream signaling Src/PI3K inhibitors, or ICAM3 inhibitor Lifitigrast prevents cancer progression in vivo. The aforementioned findings suggest a molecular model that explains how aspirin diminishes cancer cell stemness properties. These findings may provide novel targets for therapeutic strategies involving aspirin in the prevention of cancer progression. | Authentic |
Text : To investigate the expression levels of lncRNA HOXA11-AS in HCC tissues and cells, and to explore its biological role in the development and progression of HCC. We detected the relative expression level of HOXA11-AS in 72 HCC tissues and cells by the real-time quantitative PCR (qRT-PCR) assay. After interference with HOXA11-AS expression in HCC cells, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clone formation, flow cytometry and an established nude mice transplanted tumor model were used to detect the biological behavior of HCC cells. qRT-PCR and Western blotting assays were used to detect the expression level of large tumor suppressor kinases 1 (LATS1). The subcellular localization of HOXA11-AS in HCC was detected by separating nuclei from the cytoplasm. The molecular mechanism of HOXA11-AS was regulated by ribonucleoprotein immunoprecipitation-microarray (RIP-Chip) experiments. qRT-PCR assays showed that HOXA11-AS was relatively highly expressed in HCC tissues and cells. In vivo and in vitro experiments showed that HOXA11-AS could inhibit the proliferation of HCC cells, promote their apoptosis and retard the cell cycle progression from G1 to G0 phase. qRT-PCR and Western blotting assays results showed that LATS1 genes were the downstream target genes of HOXA11-AS. RIP and CHIP experiments showed that HOXA11-AS inhibited the expression of LATS1 genes by binding enhancer of zeste homolog 2 (EZH2) proteins. HOXA11-AS inhibited the malignant transcription of the LATS1 genes and promoted the malignant proliferation of HCC cells. Interactions among HOXA11-AS, PRC2, and LATS1 may provide a new target for the treatment of HCC. | Authentic |
Text : The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value. We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53 and Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. Here, we describe an adaptation of these GEM models to orthotopic allografts that uniformly develop tumors with short latency and are ideally suited for routine preclinical studies. Ovarian tumors deficient in Brca1 respond to treatment with cisplatin and olaparib, a PARP inhibitor, whereas Brca1-wild type tumors are non-responsive to treatment, recapitulating the relative sensitivities observed in patients. These mouse models provide the opportunity for evaluation of effective therapeutics, including prediction of differential responses in Brca1-wild type and Brca1-deficient tumors and development of relevant biomarkers. | Authentic |
Text : The aim of our study was to assess the efficacy, safety, and prognostic factors of drug-eluting bead transarterial chemoembolization (DEB-TACE) in Chinese hepatocellular carcinoma (HCC) patients. Patients (n=102) diagnosed as primary HCC were consecutively enrolled in this retrospective cohort study. Treatment responses were assessed following the modified Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were evaluated, and adverse events (AEs) as well as liver function-related laboratory indexes of all DEB-TACE records (N=131) were assessed. Complete response (CR) rate, objective response rate, and disease control rate were 51.0, 87.3, and 95.1%, respectively, at 1-3 months post DEB-TACE. The mean PFS and OS were 227 (95%CI: 200-255) days and 343 (95%CI: 309-377) days, respectively. Multivariate logistic regression revealed that portal vein invasion and abnormal total protein (TP) were independent predictive factors for worse CR, and multivariate Cox's regression analysis showed that multifocal disease independently correlated with shorter PFS. Most of the liver function-related laboratory indexes worsened at 1 week but recovered at 1-3 months post-treatment, only the percentage of patients with abnormal ALP increased at 1-3 months. In addition, 112 (85.5%), 84 (64.1%), 53 (40.5%), 40 (30.5%), and 16 (12.2%) patients had pain, fever, nausea, vomiting, and other AEs, respectively. DEB-TACE is efficient and safe in Chinese HCC patients, and portal vein invasion, abnormal TP level as well as multifocal disease could be used as unfavorable prognostic factors to DEB-TACE treatment. | Authentic |
Text : Remodeling and spacing factor-1 (RSF-1) is an identified tumor biomarker that is overexpressed in a variety of human cancers, but its effect on radiotherapy remains unclear. In this study, we aimed to explore the effect of RSF-1 siRNA on sensitizing cervical cancer cells to radiation and its underlying mechanism. The mRNA and protein expression of RSF-1 in tissue and cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell counting kit-8 (CCK-8) and colony formation assay were used to examine cell proliferation. Flow cytometry was used to analyzed the cell cycle and cell apoptosis. DNA damage was examined by the comet assay. ATM, ATR, CHK1, CHK2, H2AX, γH2AX and phosphorylated ATM, ATR, CHK1 and CHK2 were detected by Western blotting. γH2AX foci were demonstrated by immunofluorescence staining. RSF-1 was upregulated in cervical cancer tissue and decreased after effective treatment. RSF-1 siRNA in combination with radiation suppressed cell viability, redistributed cell cycles and also induced cell apoptosis in HeLa and SiHa cell lines. Further, knockdown of RSF-1 induced DNA damage by attenuating DNA repair capability, thereby sensitizing cervical cancer cells to radiation. These data demonstrate that RSF-1 siRNA enhanced the sensitivity of radiotherapy, and targeting RSF-1 may be a promising approach for the development of novel radiosensitizing agents for the treatment of cervical cancer. | Authentic |
Text : The Warburg effect (aerobic glycolysis) is a hallmark of cancer and is becoming a promising target for diagnosis and therapy. Phosphoglycerate kinase 1 (PGK1) is the first adenosine triphosphate (ATP)-generating glycolytic enzyme in the aerobic glycolysis pathway and plays an important role in cancer development and progression. However, how microRNAs (miRNAs) regulate PGK1-mediated aerobic glycolysis remains unknown. Here, we show that miR-16-1-3p inhibits PGK1 expression by directly targeting its 3'-untranslated region. Through inhibition of PGK1, miR-16-1-3p suppressed aerobic glycolysis by decreasing glucose uptake, lactate and ATP production, and extracellular acidification rate, and increasing oxygen consumption rate in breast cancer cells. Aerobic glycolysis regulated by the miR-16-1-3p/PGK1 axis is critical for modulating breast cancer cell proliferation, migration, invasion and metastasis in vitro and in vivo. In breast cancer patients, miR-16-1-3p expression is negatively correlated with PGK1 expression and breast cancer lung metastasis. Our findings provide clues regarding the role of miR-16-1-3p as a tumor suppressor in breast cancer through PGK1 suppression. Targeting PGK1 through miR-16-1-3p could be a promising strategy for breast cancer therapy. | Authentic |
Text : Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging. | Authentic |
Text : Abnormal expression and activation of tropomyosin-related kinase receptor B (TrkB) are observed in many pathological conditions, including many types of cancer. We try to explore the relationship between ovarian cancer and Brain-derived neurotrophic factor (BDNF), a ligand of TrkB. Human ovarian cancer cell line SKOV-3 was used in this study. qPCR, immunohistochemistry, and immunoblot were used to assay BDNF and TrkB expression level. Scratch assay was used to test the cell motility, and transwell assay was used to test the cell migration ability. We found that BDNF promotes the proliferation and invasion of human ovarian cancer SKOV-3 cells depend on the activation of TrkB. To illuminate the downstream pathway of BDNF/TrkB, we silenced AKT1 and PLCγ1 by siRNA. The functional assay showed that activated PLCγ1 signaling pathway is necessary for the proliferation and invasion of cancer cells other than the AKT pathway. Further study showed that PLCγ1 could inhibit the apoptosis of cancer cells. BDNF triggers TrkB/PLCγ1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis. | Authentic |
Text : Circular RNAs (circRNAs) play critical roles in disease incidence. However, the roles of circRNAs in colorectal cancer (CRC) progression remain largely unknown. We explored the expression of circMTO1 in CRC and elucidated the underlying molecular mechanisms. Quantitative Real-time-PCR (qRT-PCR) was used to explore circMTO1 expression in CRC tissues and cell lines. The effect of circMTO1 on the biological function of CRC cells was analyzed by Cell Counting Kit-8 (CCK-8) assay, Edu assay, colony formation assay, wound-healing assay and transwell invasion assay. Gene expression and signaling pathway were detected by qRT-PCR and Western blot. QRT-PCR showed that circMTO1 expression was significantly decreased in CRC tissues and cell lines compared with adjacent non-tumor tissues and human normal colon epithelial cell line (FHC), respectively. Patients with low circMTO1 expression were correlated with advanced TNM stage, lymph node metastasis, and poor overall survival. Function assays demonstrated that circMTO1 inhibition promoted CRC cells proliferation and invasion ability in vitro. In addition, we showed that circMTO1 inhibition could promote CRC progression via activating Wnt/β-catenin signaling pathway. We showed that circMTO1 could act as a tumor suppressor affecting the growth and invasion of CRC cells via regulating Wnt/β-catenin signaling pathway, providing a novel potential biomarker and therapeutic target for CRC treatment. | Authentic |
Text : microRNAs have been proved to function in some processes of differentiation and the effect is favorable. At present, the differentiation of stem cells is not so ideal because of the high expenses and inaccessibility. Therefore, we explored the possibility that microRNA-221 (miR-221) affects differentiation from stem cells from human deciduous tooth (SHEDs) to neurons through Wnt/β-catenin pathway via binding to CHD8. After collection of SHEDs, differentiation from SHEDs to neurons was conducted by neurotrophic factor induction method in vitro, followed by gain- and loss-of-function experiments. Expression of neuron-related genes in SHEDs was examined by immunohistochemistry. The relationship between CHD8 and miR-221 was detected by dual luciferase reporter gene assay. RT-qPCR and Western blot analysis were used to determine miR-221 expression, and the mRNA and protein expression of CHD8, Wnt/β-catenin pathway- and neuron-related genes. Cell viability, and cell cycle and apoptosis were investigated by MTT assay and flow cytometry respectively. Dual luciferase reporter assay displayed that miR-221 targeted CHD8 and then affected the differentiation progression. Results of RT-qPCR and Western blot analysis showed that expression of Wnt/β-catenin pathway-related genes increased significantly, CHD8 expression decreased in neuron-induced SHEDs after miR-221 overexpression or CHD8 silencing. In response to miR-221 overexpression and CHD8 silencing, cell viability and cell cycle entry were increased, and apoptosis was reduced. Moreover, overexpression of miR-221 or silencing of CHD8 elevated the expression of neuron-related genes in neuron-induced SHEDs. Taken together, upregulation of miR-221 promotes differentiation from SHEDs to neuron cells through activation of Wnt/β-catenin pathway by binding to CHD8. | Counterfeit |
Text : Angiogenesis is an essential process for tumor growth and metastasis, and remains a promising therapeutic target process in cancer treatment for several cancer types. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor (VEGF), was the first antiangiogenic agent approved for cancer therapy. Novel antiangiogenic agents, such as sunitinib, sorafenib, pazopanib, or vandetanib that target additional proangiogenic signaling pathways beyond VEGF, have also been approved for the treatment of various malignant diseases. While most of these agents are approved in combination with cytotoxic chemotherapy for indications including metastatic colorectal cancer, non-small-cell lung cancer, breast cancer, renal cell carcinoma (RCC), and gastric cancer, some are used as approved monotherapy for advanced RCC, hepatocellular carcinoma and medullary thyroid cancer. Major challenges to the success of antiangiogenic therapy include associated toxicity risks, limitation of efficacy through the possible development of resistance and induction or promotion of metastatic progression. Nintedanib (formally known as BIBF 1120) is a triple angiokinase inhibitor of VEGF, fibroblast growth factor, platelet-derived growth factor signaling with lesser activity against RET, Flt-3, and Src. Through this unique targeting profile nintedanib has demonstrated significant antitumor activity in several tumor types in preclinical studies. Nintedanib has also shown promising clinical efficacy in combination with docetaxel and has been approved for treating patients with locally advanced and metastatic non-small-cell lung cancer in Europe. Nintedanib has also been found to be clinically promising in terms of efficacy and safety in several other solid tumors including ovarian cancer (Phase III), RCC (Phase II), and prostate cancer (Phase II). This review article provides a comprehensive summary of the preclinical and clinical efficacy of nintedanib in the treatment of solid tumors. | Authentic |
Text : Colorectal cancer is the third most common type of cancer worldwide with high cell motility and metastatic potential. Reticulon 4C (RTN4-C) is the shortest isoform of the reticulon family protein RTN4, which may act to induce cell apoptosis and suppress tumor development. The aim of the present study was to determine the role of RTN4-C in colorectal cancer, and potentially identify a novel target for anti-tumor therapy. To investigate the biological role of RTN4-C in colorectal cancer, the expression levels of RTN4-C were initially analyzed in six colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, lentivirus-based RNA interference was utilized to knock down RTN4-C expression in RKO and DLD-1 cells with low and high levels of RTN4-C, respectively. The rate of proliferation decreased in RTN4-C silenced RKO and DLD-1 cells compared with the control, as determined using MTT and colony formation assays. Flow cytometric analysis revealed that RTN4-C knockdown in RKO cells led to cell cycle arrest at the G0/G1 phase, particularly at the sub-G1 phase representing apoptotic cells. These results indicate that RTN4-C has an important role in colorectal cancer cell growth, which may provide a potential therapeutic approach for human colorectal cancer. | Authentic |
Text : As one of the most vulnerable cancers of women, the incidence rate of breast cancer in China is increasing at an annual rate of 3%, and the incidence is younger. Therefore, it is necessary to conduct research on the risk of breast cancer, including the cause of disease and the prediction of breast cancer risk based on historical data. Data based statistical learning is an important branch of modern computational intelligence technology. Using machine learning method to predict and judge unknown data provides a new idea for breast cancer diagnosis. In this paper, an improved optimization algorithm (GSP_SVM) is proposed by combining genetic algorithm, particle swarm optimization and simulated annealing with support vector machine algorithm. The results show that the classification accuracy, MCC, AUC and other indicators have reached a very high level. By comparing with other optimization algorithms, it can be seen that this method can provide effective support for decision-making of breast cancer auxiliary diagnosis, thus significantly improving the diagnosis efficiency of medical institutions. Finally, this paper also preliminarily explores the effect of applying this algorithm in detecting and classifying breast cancer in different periods, and discusses the application of this algorithm to multiple classifications by comparing it with other algorithms. | Authentic |
Text : Metastasis is accountable for 90% of cancer deaths. During metastasis, tumor cells break away from the primary tumor, enter the blood and the lymph vessels, and use them as highways to travel to distant sites in the body to form secondary tumors. Cancer cell migration through the endothelium and into the basement membrane represents a critical step in the metastatic cascade, yet it is not well understood. This process is well characterized for immune cells that routinely transmigrate through the endothelium to sites of infection, inflammation, or injury. Previous studies with leukocytes have demonstrated that this step depends heavily on the activation status of the endothelium and subendothelial substrate stiffness. Here, we used a previously established in vitro model of the endothelium and live cell imaging, in order to observe cancer cell transmigration and compare this process to leukocytes. Interestingly, cancer cell transmigration includes an additional step, which we term 'incorporation', into the endothelial cell (EC) monolayer. During this phase, cancer cells physically displace ECs, leading to the dislocation of EC VE-cadherin away from EC junctions bordering cancer cells, and spread into the monolayer. In some cases, ECs completely detach from the matrix. Furthermore, cancer cell incorporation occurs independently of the activation status and the subendothelial substrate stiffness for breast cancer and melanoma cells, a notable difference from the process by which leukocytes transmigrate. Meanwhile, pancreatic cancer cell incorporation was dependent on the activation status of the endothelium and changed on very stiff subendothelial substrates. Collectively, our results provide mechanistic insights into tumor cell extravasation and demonstrate that incorporation is one of the earliest steps. | Authentic |
Text : Hypoxia-exposed lung cancer-released exosomal microRNA-23a (miR-23a) has been shown to enhance angiogenesis as well as vascular permeability, contributing to the close correlation between exosomal miR-23a and tumorigenesis. The current study aimed to investigate whether gastric cancer (GC) cell-derived exosomal miR-23a could induce angiogenesis and to elucidate the potential mechanisms associated with the process. Differentially expressed miRNAs in GC were initially screened from the Gene Expression Omnibus database. Target genes were selected following miRNA-mRNA prediction and subsequently verified by dual luciferase reporter assay. RT-qPCR was conducted to detect miR-23a and PTEN expression in GC tissues, cells and exosomes. Human umbilical venous endothelial cells (HUVECs) were co-cultured with GC cell-derived exosomes to assess the angiogenesis mediated by exosomes in vitro. Additionally, PTEN was overexpressed in HUVECs to analyze the mechanism by which miR-23a regulates angiogenesis. miR-23a was highly expressed in GC tissues and cells and GC cell-derived exosomes. Angiogenesis was promoted by the co-culture of HUVECs and GC cells-derived exosomes, as evidenced by the increased expression of VEGF but decreased expression of TSP-1. PTEN was targeted by miR-23a and was lowly expressed in GC tissues. In a co-culture system, miR-23a carried by GC cells-derived exosomes promoted angiogenesis via the repression of PTEN. Collectively, GC cell-derived exosomal miR-23a could promote angiogenesis and provide blood supply for growth of GC cells. This study contributes to advancement of miRNA-targeted therapeutics. | Counterfeit |
Text : Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic 'crown-like structure (CLS)' around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte-macrophage-breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1-TSC2 complex-mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte-macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin-estrogen-macrophage axis, and sirtuin 1 (SIRT1)-adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines. | Authentic |
Text : Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non-small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated. Radiation-resistant NSCLC cell lines were established. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-16-5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation-resistant cells. After being treated with different concentrations of quercetin and different doses of X-ray, cell proliferation and apoptosis were monitored by CCK-8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR-16-5p and WEE1 was verified via a dual fluorescent reporter gene assay. The expression of miR-16-5p was down-regulated in radiation-resistant cells, while the expression of WEE1 was up-regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose- and time-dependent manner. Furthermore, quercetin treatment increased the expression of miR-16-5p and decreased the expression of WEE1. The function of quercetin was reversed by miR-16-5p inhibitors or the transfection of WEE1 overexpressing plasmids. In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR-16-5p and WEE1. | Authentic |
Text : The death rate of lung cancer (LC) ranks first in the world. Changes of DNA methylation in peripheral blood may be related to malignant tumors. It is necessary to explore blood-based biomarkers of methylation to detect LC. Mass spectrometry assays were conducted to measure DNA methylation levels of seven CpG sites within FUT7 gene in the peripheral blood of 428 patients with LC, 233 patients with benign pulmonary nodule (BPN) and 862 normal controls (NC). The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using per SD change and tertiles analyses by logistic regression. The predictive ability of the seven FUT7 CpG sites and risk factors were evaluated by receiver operating characteristic curve (ROC). The methylation levels of seven CpG sites of FUT7 in LC were significantly lower than that in NC (P < 0.05). The per SD decrement of methylation level in CpG_1-7 was significantly associated with 65%, 38%, 59%, 46%, 23%, 20% and 68% higher risk for LC versus NC, respectively, and the adjusted ORs (95% CI) were 2.92 (2.17-3.96), 1.76 (1.29-2.38), 2.83 (2.09-3.82), 3.00 (2.17-4.16), 1.81 (1.35-2.43), 1.48 (1.11-1.97) and 3.04 (2.23-4.16) for the lowest tertiles of methylation level in CpG_1-7 compared with the top tertiles, respectively. The area under the curve (AUC) of FUT7_CpG_1-7 was 0.659 (CI 0.626-0.693), 0.792 (CI 0.736-0.848) and 0.729 (CI 0.665-0.792) in distinguishing LC versus NC, LUSC versus NC and LUSC versus BPN. Our study revealed an association between FUT7 hypomethylation and LC, especially for LUSC, which provides novel support for the blood-based methylation signatures as potential marker for assessing lung cancer risk. | Authentic |
Text : The purpose of this current study is to elucidate whether altered microRNA-365 (miR-365) has an association with the initiation and development of non-small-cell lung cancer (NSCLC) by targeting TRIM25 expression. The expression of miR-365 and TRIM25 in NSCLC tissues, adjacent normal tissues, and NSCLC cell lines were detected. The relationship between miR-365 expression and TRIM25 with the clinicopathological characteristics of NSCLC was analyzed. The putative binding site between miR-365 and TRIM25 was determined by luciferase activity assay. miR-365 inhibitors and miR-365 mimics were transfected to human NSCLC A549 cells, and the cell viability was detected by cell counting kit-8 assay; flow cytometry was carried out to determine cell cycle and apoptosis rate. Poorly expressed miR-365 and overexpressed TRIM25 was found in NSCLC tissues. TRIM25 was determined as a target gene of miR-365. The miR-365 and TRIM25 expression were related to the clinicopathological features of NSCLC, such as pathological classification, differentiation degree, TNM stage as well as lymph node metastasis. miR-365 suppressed the expression of TRIM25 and elevated the expression of the proapoptotic protein in NSCLC cells. Our study demonstrates that altered expression of miR-365 has a close association with the occurrence and development of NSCLC by inhibiting TRIM25 expression. | Counterfeit |
Text : The aim of the present study was to investigate the treatment effects and associated mechanism of Bak Foong pills (BFPs) combined with metformin in the treatment of polycystic ovarian syndrome (PCOS). BFPs and/or metformin were administrated to treat the PCOS rats, and the weights and morphologies of the ovary, uterus and adrenal gland were measured. The levels of fasting blood glucose (FBG), serum testosterone (T), luteinizing hormone, fasting insulin (FIN) and insulin-like growth factor-1 were also measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The expression level of androgen receptor (AR) in the ovarian tissue, and the cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) mRNA levels in the ovary and adrenal tissues were detected. The levels of T, FIN, FBG and HOMA-IR in the combination group were significantly reduced; the wet weights of the ovary and the adrenal gland were decreased significantly, while that of the uterus was increased, and the histological morphology benignly recovered. The rats of each treatment group all experienced restored ovulation. The AR expression level in the treatment group was reduced, and the P450scc mRNA levels in the ovary and the adrenal gland of the combined treatment group were decreased. BFPs combined with metformin significantly affected PCOS, and the possible mechanism involved in the treatment may have been through the reduction of P450scc generation. BFPs may reduce the androgen levels, thus allowing the ovary to restore ovulation. | Authentic |
Text : This study aims to elucidate the mechanisms by which microRNA-143-5p (miR-143-5p) targets runt-related transcription factor 2 (Runx2) in the differentiation of dental pulp stem cells (DPSCs) into odontoblasts, through regulating the osteoprotegerin receptor activator of the nuclear factor-κB ligand (OPG/RANKL) signaling pathway. Following transfection, DPSCs were divided into blank, control, miR-143-5p mimics, miR-143-5p inhibitors, miR-143-5p inhibitors + siRunx2 and siRunx2 groups. Alkaline phosphatase (ALP) activity and mineralized nodules were detected using ALP kit and alizarin red staining. Quantitative reverse transcriptase real time PCR (qRT-PCR) was conducted to measure mRNA expressions of miR-143-5p, Runx2, OPG, and RANKL. Western blotting was used to assess protein expression of odontoblast differentiation-related proteins. Transwell assay and an extracellular matrix (ECM) adhesion cell assay were employed to examine cell migration and cell adhesion. Compared with the blank group, the miR-143-5p mimics and siRunx2 groups showed decreased ALP activity, decreased mineralized nodules and displays of calcium. Fewer migrated cells, weakened cell adhesion, decreased protein expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin matrix protein 1 (DMP1), osteopontin (OPN), bone sialoprotein (BSP), osteocalcin (OCN), OPG and Runx2, and increased RANKL protein expressions were observed. Additionally, opposite results were observed in the miR-143-5p inhibitors group, demonstrating that down-regulated miR-143-5p promotes the differentiation of DPSCs into odontoblasts by enhancing Runx2 expression via the OPG/RANKL signaling pathway. Based on findings in this study, it is postulated that the enhancement of Runx2 expression via the regulation of the OPG/RANKL signaling pathway could be a beneficial approach for dental pulp regeneration. J. Cell. Biochem. 119: 536-546, 2018. © 2017 Wiley Periodicals, Inc. | Counterfeit |
Text : To explore the expression of linc00324 in papillary thyroid cancer (PTC) and its effect on the biological function of PTC cells. A total of 60 pairs of PTC and para-carcinoma normal tissues surgically excised were collected. The expression of linc00324 in PTC tissues and cells was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the expression of linc00324 in PTC cells was silenced using the small-interfering RNA (siRNA). Then, the effects of linc00324 on the PTC cell proliferation, apoptosis, and cycle and the downstream Notch signaling pathway were determined via methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, flow cytometry, and Western blotting, respectively. The expression of linc00324 was upregulated in 48 out of 60 cases of PTC tissues, and it was increased in PTC cells compared with that in human thyroid follicular epithelial cells Nthy-ori 3-1. The results of MTT assay and colony formation assay showed that the proliferation of PTC cells declined after interference in linc00324 expression. The findings of flow cytometry revealed that the cell cycle was arrested in G1/G0 phase with a higher apoptosis rate in si-linc00324 group compared with that in the si-NC group. According to the data of Western blotting, the molecular markers for the downstream Notch signaling pathway were altered after interference in linc00324 expression. The expression of linc00324 is significantly increased in PTC tissues and cells. Silencing linc00324 may inhibit the proliferation of PTC cells, arrest the cell cycle in G1/G0 phase, and promote the apoptosis by inhibiting the Notch signaling pathway. | Authentic |
Text : Antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), play a crucial role in bridging innate and adaptive immunity; thereby, innate immune checkpoint blockade-based therapy is an attractive approach for the induction of sustainable tumor-specific immunity. The interaction between the cluster of differentiation 47 (CD47) on tumor and signal-regulatory protein alpha (SIRPα) on phagocytic cells inhibits the phagocytic function of APCs, acting as a "don't eat me" signal. Accordingly, CD47 blockade is known to increase tumor cell phagocytosis, eliciting tumor-specific CD8+ T-cell immunity. Here, we introduced a nature-derived nanocage to deliver SIRPγ for blocking of antiphagocytic signaling through binding to CD47 and combined it with prophagocytic stimuli using a metabolic reprogramming reagent for APCs (CpG-oligodeoxynucleotides). Upon delivering the clustered SIRPγ variant, the nanocage showed enhanced CD47 binding profiles on tumor cells, thereby promoting active engulfment by phagocytes. Moreover, combination with CpG potentiated the prophagocytic ability, leading to the establishment of antitumorigenic surroundings. This combination treatment could competently inhibit tumor growth by invigorating APCs and CD8+ T-cells in TMEs in B16F10 orthotopic tumor models, known to be resistant to CD47-targeting therapeutics. Collectively, enhanced delivery of an innate immune checkpoint antagonist with metabolic modulation stimuli of immune cells could be a promising strategy for arousing immune responses against cancer. | Authentic |
Text : G-protein-coupled receptors (GPCRs), the largest family of cell-surface molecules involved in a number of biological and pathological processes, have recently emerged as key players in carcinogenesis and cancer progression. Orphan G protein-coupled receptors (oGPCRs) are a group of proteins lacking endogenous ligands. GPR137, one of the novel oGPCR genes, was discovered by homology screening. However, the biological role of GPR137 in cancers has not yet been discussed and is of great therapeutic interest. In this study, we knocked down GPR137 via a lentivirus system in two human pancreatic cancer cell lines BXPC-3 and PANC-1. Knockdown of GPR137 strongly inhibited cell proliferation and colony formation. Flow cytometry showed that cell cycle was arrested in the sub-G1 phase and apoptotic cells were significantly increased after GPR137 knockdown. Western blotting confirmed that GPR137 silencing induced apoptosis due to cleavage of PARP (poly ADP-ribose polymerase) and upregulation of caspase 3. Furthermore, lentivirus-mediated overexpression of GPR137 promoted the proliferation of PANC-1 cells, suggesting GPR137 as a potential oncogene in pancreatic cancer cells. Taken together, our results prove the importance of GPR137 as a crucial regulator in controlling cancer cell growth and apoptosis. | Counterfeit |
Text : MicroRNA dysregulation contributes to malignant progression, dissemination, and profound treatment resistance in multiple cancers. miR-449a is recognized as a tumor suppresser. However, the roles of miR-449a in lung cancer initiation and progression are largely unknown. Our study aims to investigate the roles and underlying mechanism of miR-449a in modulating sensitivity to ionizing radiation (IR) in non-small cell lung cancer (NSCLC). Lung cancer cells were transfected with miR-449a mimics or negative control and exposed to IR; the levels of target protein, glycolysis, cell viability, apoptosis, and DNA damage were examined. miR-449a was suppressed in lung cancer tissues and cancer cells (A549 and H1299). IR exposure significantly increased the expression of miR-449a in A549 cells at doses ranging from 4 to 8 Gy at 24 h, whereas no significant change in miR-449a was found in H1299 cells after IR. When A549 cells were exposed to IR at a dose of 8 Gy, the miR-449a level only had an acute increase within 12 h. miR-449a restoration dramatically suppressed IR-induced cell apoptosis and DNA damage in both A549 and H1299 cells. Bioinformatics analysis indicated that lactate dehydrogenase A (LDHA) was a potential target of miR-449a. miR-449a mimic transfection substantially suppressed the LDHA expression and production of lactate catalyzed by LDHA as well as glucose uptake. We confirmed that miR-449a could bind to the 3'-UTR of LDHA mRNA using luciferase reporter assay. LDHA siRNA-transfected cells showed enhanced cell apoptosis and DNA damage in response to IR exposure. miR-449a upregulation enhanced IR sensitivity of lung cancer cells by suppressing LDHA and the subsequent glycolysis. | Authentic |
Text : Although emerging evidence has revealed that microRNAs (miRNAs) dysregulation contribute to carcinogenesis, the mechanism underlying their roles in renal cell carcinoma (RCC) is unclear. The purpose of the current study was to analyze the association of miR-200a-3p expression with RCC and to understand potential novel target genes, functions and mechanisms of miR-200a-3p in RCC. MiR-200a-3p expression levels were first measured by quantitative real-time polymerase chain reaction and in situ hybridization in pairs of RCC tissue samples. Next, the potential miR-200a-3p target gene was analyzed using a combination of computer-aided algorithms, luciferase reporter assays and Western blot analysis. Finally, the biological roles of miR-200a-3p in RCC tumorigenesis were investigated both in vitro by 5-ethynyl-20-deoxyuridine, apoptosis assay and transwell assay, as well as in vivo using a xenograft mouse model. Our results demonstrated that miR-200a-3p was remarkably downregulated in RCC tissues compared with normal adjacent tissue, and CBL is a direct target of miR-200a-3p. An inverse correlation between miR-200a-3p and CBL was observed in RCC tissue samples. Mechanistic investigations revealed that ectopic expression of miR-200a-3p in RCC cell lines suppressed cell proliferation and migration and enforced cell apoptosis by directly inhibiting CBL in vitro and in vivo, whereas silencing miR-200a-3p resulted in the opposite effects. Additionally, overexpressing CBL abolished the effects induced by miR-200a-3p overexpression. Taken together, our results show that the miR-200a-3p/CBL regulation axis is a novel mechanism underlying RCC pathogenesis and may serve as a candidate biomarker and therapeutic target in RCC. | Authentic |
Text : The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression. | Authentic |
Text : To explore the differentially expressed microRNAs (DEmiRs) derived from plasma exosomes related to radiotherapy resistance and their corresponding pathways in non-small-cell lung cancer (NSCLC). Plasma samples from NSCLC patients were retrieved and analyzed. The patients were divided into 3 groups based on the tumor regression grade criteria, assessed by radiological imaging after radiotherapy. TRG1 referred to tumor shrinkage of ≤30% after radiotherapy, TRG2 as 30% < TRG < 50%, and TRG3 as TRG ≥ 50%. High-throughput sequencing and bioinformatics analysis were used to compare the DEmiRs between the three groups. The miRanda, PITA, and RNAhybrid software were used to identify potential target genes of the DEmiRs. GO function enrichment and KEGG pathway enrichment analyses were performed on the target gene set. There were 24 DEmiRs (12 were upregulated and 12 downregulated) between the TRG1 and TRG2 groups, 11 between the TRG1 and TRG3 groups (6 upregulated and 5 downregulated), and 35 between the TRG2 and TRG3 groups. The common DEmiRs between the three groups were miR-92a-3p. GO analysis showed that the target genes of the DEmiRs were mainly enriched in unicellular organism processes, cell transformation, cell localization, and their establishment. KEGG enrichment analysis showed that target genes were significantly enriched in the Ras signaling pathway and associated with endocytosis. Among the 135 identified target genes of miR-92a-3p, 4 were involved in the PI3K-Akt signaling pathway (the downstream pathway of the Ras gene) and 3 in the cAMP signaling pathway (the upstream pathway of the Ras gene). Further, 2 other target genes were involved in the Rap1 signaling pathway (the upstream pathway of PI3K-Akt). By assessing the expression and functional profile of DEmiRs in the plasma exosomes of NSCLC patients after radiotherapy, miR-92a-3p was identified as a promising target affecting radiotherapy outcomes through the Ras signaling pathway. | Authentic |
Text : ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1). The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. Fe-S clusters were the key domains in ABCE1 involved in binding to β-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with β-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis. | Authentic |
Text : Prisconnatanones A (Priscon-A) is a rare tetrahydroanthraquinone isolated from herbal Prismatomeris connate. In this study, we examine its anti-tumour activity on human laryngocarcinoma HEp-2 cells in vitro. The CCK-8 assay was performed to evaluate its cytotoxicity. Cell cycle and apoptosis were analysed using flow cytometric analysis. Here, we showed Priscon-A inhibited the proliferation of HEp-2 cells in a dose-dependent manner, and at 5 μM it almost completely inhibited cell growth. Its cytotoxicity was associated with the cell cycle arrest at G2/M phase. The Annexin V-FITC/PI binding assay showed that the cell death induced by Priscon-A was associated with apoptosis. And, western blot analysis revealed that the levels of the apoptosis protein, cleaved caspase-3, PARP, p21 and Bax protein increased, while the level of anti-apoptosis protein Bcl-2 decreased.. These data demonstrated that Priscon-A significantly inhibited HEp-2 cell growth, induced the cell cycle arrest at the G2/M phase and efficiently induced cell apoptosis. | Authentic |
Text : Chemotherapy-induced dilated cardiomyopathy (CI-DCM) is a well-recognized phenotype of non-ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes. However, a detailed comparison between idiopathic DCM (iDCM) and CI-DCM is still lacking. All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analysed. CI-DCM and iDCM were defined according to current recommendations. The primary study outcome measure was all-mortality death and secondary outcomes were a) a composite of cardiovascular death/heart-transplantation/ventricular-assist-device implantation, and b) major ventricular arrhythmias. The study included 551 patients (499 iDCM and 52 CI-DCM). At enrolment, compared with iDCM, CI-DCM patients were older (51 ± 14 years vs. 58 ± 3 years, respectively, P < 0.001) and had a higher left ventricular ejection fraction (32% ± 9 vs. 35% ± 10, respectively, P = 0.03). Over a median follow-up of 90 months (IQR 54-140 months), CI-DCM patients had a higher incidence of all-cause mortality compared with iDCM (36.5% vs. 8.4% in CI-DCM and iDCM respectively, P < 0.001), while the incidence of major ventricular arrhythmias was higher in the iDCM group compared with CI-DCM (4% vs. 0%, in CI-DCM and iDCM respectively, P = 0.03). The risk of the composite outcome was comparable between the two groups (P = 0.91). At Cox multivariable analysis, the diagnosis of CI-DCM emerged as independently associated to primary outcome (HR 6.42, 95% C.I. 2.52-16.31, P < 0.001). In a well-selected DCM cohort, patients with a chemotherapy-induced aetiology had a higher incidence of all-cause mortality compared with iDCM. Conversely, the incidence of life-threatening ventricular arrhythmic events was higher among patients with iDCM. | Authentic |
Text : BACKGROUND The aim of this study was to construct a nomogram to predict the prognosis of patients with gastrointestinal stromal tumor (GIST). MATERIAL AND METHODS We enrolled 4086 GIST patients listed in the SEER database from 1998 to 2015. They were separated to 2 groups: an experimental group (n=2862) and a verification group (n=1224). A nomogram was constructed by using statistically significant prognostic factors. RESULTS A nomogram that included age, sex, marital status, tumor location, grade, SEER stage, tumor size, and surgical management was developed. It can be used to predict overall survival (OS), while adding AJCC 7th TNM stage can predict cancer-specific survival (CSS). The C-index used to forecast OS and CSS nomograms was 0.778 (95% CI, 0.76-0.79) and 0.818 (95% CI, 0.80-0.84), respectively. CONCLUSIONS The nomogram can effectively predict 3- and 5-year CSS in patients with GIST, and its use can improve clinical practice. | Authentic |
Text : Cancer cells generally harbor hundreds of alterations in the cancer genomes and act as crucial factors in the development and progression of cancer. Gene alterations in the cancer genome form genetic interactions, which affect the response of patients to drugs. We developed an algorithm that mines copy number alteration and whole-exome mutation profiles from The Cancer Genome Atlas (TCGA), as well as functional screen data generated to identify potential genetic interactions for specific cancer types. As a result, 4,529 synthetic viability (SV) interactions and 10,637 synthetic lethality (SL) interactions were detected. The pharmacogenomic datasets revealed that SV interactions induced drug resistance in cancer cells and that SL interactions mediated drug sensitivity in cancer cells. Deletions of HDAC1 and DVL1, both of which participate in the Notch signaling pathway, had an SV effect in cancer cells, and deletion of DVL1 induced resistance to HDAC1 inhibitors in cancer cells. In addition, patients with low expression of both HDAC1 and DVL1 had poor prognosis. Finally, by integrating current reported genetic interactions from other studies, the Cancer Genetic Interaction database (CGIdb) (http://www.medsysbio.org/CGIdb) was constructed, providing a convenient retrieval for genetic interactions in cancer. | Authentic |
Text : To observe the short-term and long-term curative effects of partial hepatectomy on ruptured hemorrhage of primary liver cancer after transcatheter arterial embolization (TAE). A total of 150 patients with primary liver cancer treated in the hospital were enrolled as research objects between February 2018 and February 2021, including 75 cases undergoing TAE in the TAE group and the other 75 cases undergoing elective partial hepatectomy after TAE in the combination group. The surgical related indexes (leaving bed time, discharge time, success rate of hemostasis, lesion clearance rate), mean arterial pressure (MAP), heart rate (HR), hemoglobin, and liver function indexes (serum alpha-fetoprotein (AFP), albumin (ALB), total bilirubin (TBIL)) before and after treatment, postoperative complications, survival rate, and recurrence rate at 1 year after surgery between the two groups were compared. Compared with the TAE group, hospitalization time was shorter (P < 0.05), the success rate of hemostasis and lesions clearance rate were higher in the combination group (P < 0.05). After surgery, levels of HR and serum AFP were significantly decreased, while levels of MAP, hemoglobin, serum ALB, and TBIL were significantly increased in both groups. The levels of HR and serum AFP in the combination group were lower than those in the TAE group, while levels of MAP, hemoglobin, serum ALB, and TBIL were higher than those in the TAE group (P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P < 0.05). Compared with the TAE group, the recurrence rate was lower, and the survival rate was higher in the combination group at 1 year after surgery (P < 0.05). Partial hepatectomy can effectively improve hemostatic effect and liver function in ruptured hemorrhage of primary liver cancer after TAE, increase survival rate, and reduce postoperative recurrence rate. | Authentic |
Text : Lymphocyte antigen 6 complex, locus E (LY6E) is a member of the lymphostromal cell membrane Ly6 superfamily protein. The present study investigated the clinical significance and potential biological function of LY6E in gastric cancer (GC). LY6E mRNA and protein expressions in human GC tissues and GC cells were tested. Relationship between LY6E expression and the GC patients' clinicopathologic characteristics was analyzed. LY6E was silenced by siRNA in the cultured GC cells. The RNA expression microarray profiling assay results demonstrated that LY6E mRNA was significantly increased in multiple human GC tumor tissues. Immunohistochemistry (IHC) staining analysis revealed that 59 of 75 (78.7%) GC specimens were LY6E positive. LY6E over-expression in human GC was correlated with the histology grade, AJCC stage, N classification, lymphatic invasion, and tumor location. Notably, functional LY6E expression was also detected in AGS and other established GC cell lines. LY6E knockdown by targeted-siRNA inhibited AGS cell survival and proliferation. Meanwhile, the LY6E siRNA induced G1-S cell cycle arrest and apoptosis in AGC cells. Additionally, AGC cell migration was also inhibited by LY6E knockdown. Expressions of tumor-suppressing proteins, including PTEN (phosphatase and tensin homolog) and E-Cadherin, were increased in LY6E-silenced AGS cells. LY6E over-expression in GC is potentially required for cancer cell survival, proliferation and migration. | 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 : To study the impact of treatment strategy on achieving and sustaining disease-modifying antirheumatic drug (DMARD)-free remission in patients with rheumatoid arthritis (RA). Two hundred seventy-nine RA patients (median follow-up 7.8 years) were studied. Of these, 155 patients participated in a disease activity score (DAS) < 1.6 steered trial aimed at DMARD-free remission. Initial treatment comprised methotrexate with high-dose prednisone (60 mg/day) and a possibility to start biologicals after 4 months. In the same period and hospital, 124 patients were treated according to routine care, comprising DAS < 2.4 steered treatment. Percentages of DMARD-free remission (absence of synovitis for ≥ 1 year after DMARD cessation), late flares (recurrence of clinical synovitis ≥ 1 year after DMARD cessation), and DMARD-free sustained remission (DMARD-free remission sustained during complete follow-up) were compared between both treatment strategies. Patients receiving intensive treatment were younger and more often ACPA-positive. On a group level, there was no significant association between intensive treatment and DMARD-free remission (35% vs 29%, corrected hazard ratio (HR) 1.4, 95%CI 0.9-2.2), nor in ACPA-negative RA (49% versus 44%). In ACPA-positive RA intensive treatment resulted in more DMARD-free remission (25% vs 6%, corrected HR 4.9, 95%CI 1.4-17). Intensive treatment was associated with more late flares (20% versus 8%, HR 2.3, 95%CI 0.6-8.3). Subsequently, there was no difference in DMARD-free sustained remission on a group level (28% versus 27%), nor in the ACPA-negative (43% versus 42%) or ACPA-positive stratum (17% versus 6%, corrected HR 3.1, 95%CI 0.9-11). Intensive treatment did not result in more DMARD-free sustained remission, compared to routine up-to-date care. The data showed a tendency towards an effect of intensive treatment in ACPA-positive RA; this needs further investigation. | Authentic |
Text : Immune checkpoints in solid tumors serve important roles in metastasis. The present study was designed to explore the expression of programmed cell death protein 1 (PD-1) on peripheral blood T-cell subsets and its role in the clinicopathological features and prognosis of patients with metastatic gastric cancer. The expression of PD-1 in peripheral blood T-cell subsets was detected in 100 metastatic gastric cancer patients prior to the first line chemotherapy by flow cytometric analysis. The potential associaton between the peripheral blood T-cell subsets PD-1 level and the clinicopathological features of patients with metastatic gastric cancer and the clinical outcomes was analyzed. The percent of high PD-1 expressed cluster of differentiation (CD)3+, CD3+CD4+ and CD3+CD8+ T-cells was 20.4, 13.0 and 9.4%, respectively in patients with metastatic gastric cancer. The overall survival (OS) and progression-free survival (PFS) rate of the 100 patients with metastatic gastric cancer was 12.2 and 3.9 months, respectively. Kaplan-Meier curve with long-rank analysis indicated that patients with higher PD-1+/CD3+, PD-1+/CD3+CD4+ and PD-1+/CD3+CD8+ levels had a worse prognosis (all P<0.05). Univariate and multivariate analysis revealed that high PD-1+/CD3+ [hazard ratio (HR), 2.145; P=0.015], high PD-1+/CD3+CD4+ (HR, 1.866; P=0.034) and high PD-1+/CD3+CD8+ (HR, 1.817; P=0.033) level in peripheral blood were independent risk factors for predicting the survival time of patients with metastatic gastric cancer. High PD-1+/CD3+, high PD-1+/CD3+CD4+ and high PD-1+/CD3+CD8+ expression conferred a lower overall survival rate in patients with metastatic gastric cancer. These results suggest that high PD-1 expression on peripheral blood T-cell subsets may potentially be novel prognostic biomarker for metastatic gastric cancer. | Authentic |
Text : Cervical cancer is one of the most common gynecological tumors in females. DNA methylation alteration is a type of epigenetic decoration that controls the gene transcriptional regulation and is essential for the pathological progression of cervical cancer to reflect the prognosis and therapeutic sensitivity in clinical practice. Beyond DNA methylation, DNA hydroxymethylation considered as a more stable biomarker draws the outline of the reversible cycle from DNA methylation and demethylation. However, the landscape of 5-hydroxymethylcytosine (5hmC) distributed in the genome is never characterized in cervical cancer. In this study, we presented the whole 5-methylcytosine (5mC) and 5hmC profile in cervical cancer of I-IIa and IIb to IV stages and cervicitis tissues as control by dot plot assay and immunohistochemistry. We observed that the total 5mC was up-regulated while 5hmC was down-regulated in cervical cancer group compared to the control group. Furthermore, we investigated the distribution of 5mC and 5hmC on genomic DNA by MeDIP- and hMeDIP-Seq. 53 differential methylation/hydromethylation regions (DMRs/DHMRs) displayed a continuously increasing or decreasing trend of 5mC or 5hmC from cervicitis to I-IIa and from I-IIa to IIb-IV stages of cervical cancer. Thirty-seven DMRs and DHMRs have a similar variation trend while the other 8 have the opposite trend compared between CSCC and cervicitis. Moreover, the DMR/DHMR associated genes were closely related to Wnt, MAPK, Rap1 and other important signaling pathways. Finally, 5hmC beyond 5mC at the genes such as ACTG1, SALL3, DNAJA3, SERPINB6, CDC14B and CALN1 were considered as the putative novel hallmarks for cervical cancer diagnosis and prognosis. Altogether, this study first describes the DNA hydroxymethylation atlas of cervical cancer and shows a list of novel genes transcriptionally regulated by DNA methylation and hydroxymethylation. | Authentic |
Text : Semaphorin-3A (Sema3A) and vascular endothelial growth factor (VEGF165) are ligands of neuropilin-1 (NRP-1 or CD304) and are related to immunoregulation and tumor angiogenesis, respectively. However, possible interactions between NRP-1 and Sema3A and VEGF165 in acute leukemia remain unclear, especially whether Sema3A plays a role in acute leukemia. In this study, both of the proportion of regulatory T cells (Tregs) and their expression of NRP-1 were found to increase in acute leukemia patients compared with healthy controls. In contrast, lower mRNA and plasma levels of Sema3A were detected in the acute leukemia patients. In vitro, the addition of exogenous Sema3A inhibited the expression of NRP-1 on Tregs and it promoted apoptosis of leukemia cells. However, in the presence of anti-Sema3A antibody, the effect of rhSema3A on NRP-1 expression was reversed. These results suggest that Sema3A promotes apoptosis in leukemia cells by inhibiting expression of NRP-1, and thus, represents a tumor suppressor protein with a role in the pathogenesis of acute leukemia. Consequently, NRP-1/Sema3A signaling may represent a novel target for the treatment of acute leukemia and should be further studied. Anat Rec, 302:1127-1135, 2019. © 2018 Wiley Periodicals, Inc. | Authentic |
Text : This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).
This article has been retracted at the request of the Editor-in-Chief as there are concerns about the reliability of the results included in the article. The journal was initially contacted by the corresponding author to request the retraction of the article.
Given the comments of Dr Elisabeth Bik https://scienceintegritydigest.com/2020/02/21/the-tadpole-paper-mill/ regarding this article, the journal requested the author to provide the raw data. However, the author was not able to fulfil this request. | Authentic |
Text : Since the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis. A GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis. miR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p. The plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients. | Authentic |
Text : Hepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H2O2-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial-mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation. | Authentic |
Text : Although the development of drugs that control Ras is an emerging topic in cancer therapy, no clinically applicable drug is currently available. We have previously utilized knowledge of the Wnt/β-catenin signaling-dependent mechanism of Ras protein stability regulation to identify small molecules that inhibit the proliferation and transformation of various colorectal cancer (CRC) cells via degradation of both β-catenin and Ras. Due to the absence of Ras degradation in cells expressing a nondegradable mutant form of β-catenin and the need to determine an alternative mechanism of Ras degradation, we designed a cell-based system to screen compounds that degrade Ras independent of the Wnt/β-catenin signaling pathway. A cell-based high-content screening (HCS) system that monitors the levels of EGFP-K-RasG12V was established using HCT-116 cells harboring a nondegradable mutant CTNNB1 (ΔS45). Through HCS of a chemical library composed of 10,000 compounds and subsequent characterization of hits, we identified several compounds that degrade Ras without affecting the β-catenin levels. KY7749, one of the most effective compounds, inhibited the proliferation and transformation of CRC cells, especially KRAS-mutant cells that are resistant to the EGFR monoclonal antibody cetuximab. Small molecules that degrade Ras independent of β-catenin may able to be used in treatments for cancers caused by aberrant EGFR and Ras. | Authentic |
Text : Background: Stereotactic radiotherapy treats hepatocellular carcinoma (HCC) at different stages effectively and safely. Besides its direct killing of cancer cells, radiotherapy stimulates host immunity against hepatoma. However, the role of myeloid-derived suppressor cells (MDSCs) in on-target and off-target anti-HCC effects induced by hypofractionated irradiation (IR) is unclear. Methods and Materials: Hepa1-6 and H22 allogeneic transplanted tumors on hind limbs of C57BL/6 and Institute of Cancer Research (ICR) mice, respectively, were irradiated with 0, 2.5, 4, 6, or 8 Gy/fraction until the total dose reached 40 Gy. The off-target effect induced by the IR was investigated by subsequently inoculating the same HCC cells subcutaneously on the abdomen. MDSCs in peripheral blood and tumor tissues were measured by flow cytometry or immunofluorescence microscopy analysis. IL-6, regulated on activation normal T cell expressed and secreted (RANTES), and granulocyte colony-stimulating factor (G-CSF) in irradiated mouse plasma and hepatoma cell cultures were measured with ELISA kits. Conditioned media (CM) from irradiated HCC cell cultures on bone marrow cell differentiation and MDSC proliferation were examined by co-culture and flow cytometry. Results: Our study showed that the IR of primarily inoculated HCC on hind limbs created an "in situ tumor vaccine" and triggered the antitumor immunity. The immunity was capable of suppressing the growth of the same type of HCC subcutaneously implanted on the abdomen, accompanied with reduced MDSCs in both blood and tumors. The decreased MDSCs were associated with low plasma levels of IL-6, RANTES, and G-CSF. The cytokines IL-6 and RANTES in the CM were lower in the high single IR dose group than in the control groups, but G-CSF was higher. The CM from high single-dose IR-Hepa1-6 cell culture reduced the differentiation of C57BL/6 mouse bone marrow cells into MDSCs, whereas CM from high single-dose IR-H22 cells reduced the proliferation of MDSCs, which might be due to the decreased p-STAT3 in bone marrow cells. Conclusions: The hypofractionated IR on transplanted tumors at the primary location exerted a strong antitumor effect on the same tumor at a different location (off target). This abscopal effect is most likely through the reduction of MDSCs and decrease of IL-6, RANTES, and G-CSF. | Authentic |
Text : Ubiquitin-specific protease 1 (USP1) is a deubiquitinase involved in DNA damage repair by modulating the ubiquitination of major regulators, such as PCNA and FANCD2. Because USP1 is highly expressed in many cancers, dysregulation of USP1 contributes to cancer therapy. However, the role of USP1 and the mechanisms underlying chemotherapy remain unclear. In this study, we found high USP1 expression in tumor tissues and that it correlated with poor prognosis in RCC. Mechanistically, USP1 enhanced survivin stabilization by removing ubiquitin. Pharmacological inhibitors (ML23 and pimozide) and siRNA targeting USP1 induced downregulation of survivin expression. In addition, ML323 upregulated DR5 expression by decreasing miR-216a-5p expression at the post-transcriptional level, and miR-216a-5p mimics suppressed the upregulation of DR5 by ML323. Inhibition of USP1 sensitized cancer cells. Overexpression of survivin or knockdown of DR5 markedly prevented the co-treatment with ML323 and TRAIL-induced apoptosis. These results of in vitro were proved in a mouse xenograft model, in which combined treatment significantly reduced tumor size and induced survivin downregulation and DR5 upregulation. Furthermore, USP1 and survivin protein expression showed a positive correlation, whereas miR-216a-5p and DR5 were inversely correlated in RCC tumor tissues. Taken together, our results suggest two target substrates of USP1 and demonstrate the involvement of survivin and DR5 in USP1-targeted chemotherapy. | Authentic |
Text : The high incidence rates of lung cancer have resulted in multiple progressions in cancer research leading to the development of novel therapeutic strategies. The three main branches of cancer research where improvements are being made are surgery, chemotherapy, and radiotherapy. These research developments have significantly improved the survival rates of cancer patients as most of these therapeutic options target specific molecules involved in cancer progression and metastasis. Experimental research has successfully identified potentially important molecules responsible for cancer progression. Further, the above molecular markers of disease are clinically approved biomolecules of significant prognostic value. The above molecular biomolecules also helped in rapid identification of subgroups of patients who need immediate emergency treatment. Hypoxia is one of such conditions where the human system is deprived of an adequate oxygen supply and requires immediate treatment. Hypoxia markers have been proved to be beneficial in the timely management of cancer. The present review is focused on the latest updates in the area of hypoxia related to markers in the prognosis of lung cancer. | Authentic |
Text : MicroRNAs has been proved to play vital roles in many biological processes. In the present study, the expression profile of oncogenic miR-155 in the activated antitumor cytotoxic T lymphocytes generated by the fusion of dendritic cells with breast carcinoma cells has been demonstrated. Expression profile of oncogenic miR-155 was noted in antitumor cytotoxic T lymphocytes, which was generated by the fusion of dendritic cells (DC) with breast carcinoma cells (MCF-7). The fused cells were used to induce and generate antitumor CTL with the standard procedure. Flow cytometry, as well as qPCR analysis, were performed to identify the expression profile of oncogenic miR-155 in the generated antitumor CTL against breast cancer. Compared with controls, the presence of MUC-1 and MHC-II in the DC/MCF-7 fused cells was confirmed by flow cytometry analysis. qPCR experimental results conclude that oncogenic miR-155 level was decreased in the antitumor CTL generated against breast cancer cells. We observed that the oncogenic miR-155 level was down-regulated in the antitumor CTL against breast cancer, and it may be used as the effective treatment to eliminate the malignant cells in the breast cancer patients. | Authentic |
Text : Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment. | Authentic |
Text : E2F3 is a transcription factor that may initiate tumorigenesis if overexpressed. Previously, we demonstrated that E2F3 mRNA is overexpressed in breast cancer and that E2F3 overexpression results in centrosome amplification and unregulated mitosis, which can promote aneuploidy and chromosome instability to initiate and sustain tumors. Further, we demonstrated that E2F3 leads to overexpression of the mitotic regulator Shugoshin-1, which until recently had unknown roles in cancer. This study aims to evaluate the roles of E2F3 and Shugoshin-1 in breast cancer metastatic potential. Here we demonstrated that E2F3 and Shugoshin-1 silencing leads to reduced cell invasion and migration in two mesenchymal triple-negative breast cancer (TNBC) cell lines (MDA-MB-231 and Hs578t). Moreover, E2F3 and Shugoshin-1 modulate the expression of epithelial-to-mesenchymal transition-associated genes such as Snail, E-Cadherin, and multiple matrix metalloproteinases. Furthermore, E2F3 depletion leads to reductions in tumor growth and metastasis in NOD-scid Gamma mice. Results from this study suggest a key role for E2F3 and a novel role for Shugoshin-1 in metastatic progression. These results can further help in the improvement of TNBC targeted therapies by interfering with pathways that intersect with the E2F3 and Shugoshin-1 signaling pathways. | Authentic |
Text : To investigate the role of phosphatidylinositol-3-kinase protein kinase B (PI3K/Akt) signaling pathway in the apoptosis of H1299 lung cancer cells induced by epigallocatechin gallate (EGCG). H1299 lung cancer cells were treated with EGCG at a dose of 10 µM, 20 µM, and 40 µM, respectively. Cell culture was performed for 72 h and then: 1, cell proliferation was detected by MTT assay; 2, cell apoptosis rate was detected by flow cytometry; 3, expression of Caspase-3, Bax, and Bcl-2 was detected by Western blot; 4, expression of PI3K, p-PI3K, Akt, and p-Akt was detected by Western blot. The proliferation of H1299 cells was significantly inhibited 72 h after treatment with different doses of EGCG, and cell apoptosis rate was significantly increased (p<0.05). Compared with those in the control group, expression of PI3K and Akt in the lung cancer cells H1299 after EGCG treatment showed no significant differences (p>0.05), while expression levels of p-PI3K and p-Akt were significantly reduced (p<0.05). EGCG can inhibit the proliferation and induce apoptosis of H1299 lung cancer cells, and the effect is related to the inhibition of the activation of PI3K/Akt signaling pathway. | Authentic |
Text : Recent studies have revealed the important role of long noncoding RNAs (lncRNAs) in the progression of tumorigenesis. This study aimed to identify the biological function of lncRNA small nucleolar RNA host gene 7 (SNHG7) in the progression of nasopharyngeal carcinoma (NPC). LncRNA SNHG7 expressions in NPC cell lines and 50 paired NPC tissue samples were detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Transwell assay, wound healing assay and proliferation assay were conducted to evaluate the in vitro function of SNHG7 in NPC cells. Xenograft model was established for determining the in vivo effect of SNHG7 on tumor formation and metastasis of NPC. The underlying mechanism of SNHG7 in mediating the progression of NPC was explored by RT-qPCR and Western blot. SNHG7 expression was remarkably downregulated in NPC tissues compared with that in adjacent normal samples. Knockdown of SNHG7 attenuated proliferation, invasion and migration of NPC cells. Moreover, tumor size and the number of metastatic nodules were reduced in mice administrated with NPC cells transfected with sh-SNHG7. Knockdown of SNHG7 downregulated ROCK1 at mRNA and protein level. Besides, the expression of ROCK1 in tumor tissues was positively correlated to SNHG7 expression. Knockdown of SNHG7 inhibits migration, invasion and proliferation of NPC cells through downregulating ROCK1, which may offer a new therapeutic intervention for NPC patients. | Counterfeit |
Text : Ischaemia/reperfusion (I/R)-induced hepatic injury is regarded as a main reason of hepatic failure after transplantation or lobectomy. The current study aimed to investigate how the opioid analgesic remifentanil treatment affects I/R-induced hepatic injury and explore the possible mechanisms related to HIF1α. Initially, an I/R-induced hepatic injury animal model was established in C57BL/6 mice, and an in vitro hypoxia-reoxygenation model was constructed in NCTC-1469 cells, followed by remifentanil treatment and HIF1α silencing treatment. The levels of blood glucose, lipids, alanine transaminase (ALT) and aspartate transaminase (AST) in mouse serum were measured using automatic chemistry analyser, while the viability and apoptosis of cells were detected using CCK8 assay and flow cytometry. Our results revealed that mice with I/R-induced hepatic injury showed higher serum levels of blood glucose, lipids, ALT and AST and leukaemia inhibitory factor (LIF) expression, and lower HIF1α and ZEB1 expression (P < .05), which were reversed after remifentanil treatment (P < .05). Besides, HIF1α silencing increased the serum levels of blood glucose, lipids, ALT and AST (P < .05). Furthermore, hypoxia-induced NCTC-1469 cells exhibited decreased HIF1α and ZEB1 expression, reduced cell viability, as well as increased LIF expression and cell apoptosis (P < .05), which were reversed by remifentanil treatment (P < .05). Moreover, HIF1α silencing down-regulated ZEB1 expression, decreased cell viability, and increased cell apoptosis (P < .05). ZEB1 was identified to bind to the promoter region of LIF and inhibit its expression. In summary, remifentanil protects against hepatic I/R injury through HIF1α and downstream effectors. | Counterfeit |
Text : MiR-638 is constantly downregulated and serves as a tumor suppressor in various cancers. Its role in gliomas remains unclear. This study is designed to investigate the clinical significance and the pathogenic role of miR-638 in human gliomas. Quantitative Real-time PCR was performed to analyze the expression of miR-638 in the tumor and adjacent tissues of 24 glioma patients. The association between the expression of miR-638 and clinical features were examined. Survival of patients was studied by Kaplan-Meier curves. The impact of miR-638 on cell growth and apoptosis was determined by CCK-8 assay, colony formation assay, cell cycle analysis and Annexin V-FITC-PI apoptosis assay. The effect of miR-638 on HOXA9 was determined by luciferase assay and Western blot. The effect of miR-638 and HOXA9 on expression of oncogenes, Cyclin D1 and C-MYC was determined by Western blot. MiR-638 expression was constantly downregulated in glioma tumor tissue, which is negatively correlated with the WHO grade. MiR-638 expression was associated with clinical features such as tumor size, KPS score and WHO grade. Patients with low miR-638 had a worse overall survival than those with high expression. Experimentally, miR-638 directly targeted HOXA9 to suppress its expression, leading to attenuations of cell proliferation, colony formation and cell cycle progression and enhanced basal apoptosis level. MiR-638/HOXA9 axis also suppressed the expression of Wnt/beta-catenin-regulated oncogenes, Cyclin D1 and C-MYC. MiR-638 is a constantly downregulated microRNA in gliomas and is associated with its prognosis. MiR-638 regulates cellular malignancy of gliomas through targeting HOXA9. Thus, miR-638/HOXA9 signaling axis may have therapeutic potential in gliomas. | Authentic |
Text : Serous ovarian cancer is a major gynecologic malignancy with a poor 5‑year survival rate. However, little is known regarding the behavior and genetics of ovarian tumorigenesis. MicroRNAs (miRNAs) have been shown to be dysregulated in ovarian carcinomas. To assess the miRNA expression profiles in serous ovarian cancer, we defined the patterns of miRNA expression in 100 formalin‑fixed, paraffin‑embedded ovarian cancer tissues blocks as well as 50 corresponding normal oviduct tissues using miRNA microarray. MiRNA expression profiling showed that 63 miRNAs were downregulated and 43 miRNAs were upregulated in serous ovarian cancer tissues compared with control tissues. The expression of five dysregulated miRNAs was validated using quantitative polymerase chain reaction (RT‑qPCR). GO term and pathway analysis revealed that the biological process of the cell cycle was significantly enriched and the MAPK signaling pathway was highly involved in the progression of ovarian cancer. The results suggested that the aberrant expression of miRNAs is involved in ovarian carcinogenesis and thus these miRNAs may function as diagnostic and prognostic biomarkers. | Authentic |
Text : Ferroptosis is a newly identified cell death mechanism and potential biomarker for hepatocellular carcinoma (HCC) therapy; however, its clinical relevance and underlying mechanism remain unclear. In this study, transcriptome and methylome data from 374 HCC cases were investigated for 41 ferroptosis-related genes to identify ferroptosis activity-associated subtypes. These subtypes were further investigated for associations with clinical and pathological variables, gene mutation landscapes, deregulated pathways and tumour microenvironmental immunity. A gene expression signature and predictive model were developed and validated using an additional 232 HCC cases from another independent cohort. Two distinct ferroptosis phenotypes (Ferroptosis-H and Ferroptosis-L) were identified according to ferroptosis gene expression and methylation in the patients with HCC. Patients with the Ferroptosis-H had worse overall and disease-specific survival, and the molecular subtypes were significantly associated with different clinical characteristics, mRNA expression patterns, tumour mutation profiles and microenvironmental immune status. Furthermore, a 15-gene ferroptosis-related prognostic model (FPM) for HCC was developed and validated which demonstrated accurate risk stratification ability. A nomogram included the FPM risk score, ECOG PS and hepatitis B status was developed for eventual clinical translation. Our results suggest that HCC subtypes defined by ferroptosis gene expression and methylation may be used to stratify patients for clinical decision-making. | Authentic |
Text : Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins. CDDP, tunicamycin, and BEZ235 acted synergistically to enhance these effects. We also detected lower expression of the ERS-related proteins caspase-3, LC3 II and Beclin 1 in ovarian cancer tissues than adjacent normal tissues. By contrast, expression of Bcl-2 and PI3K/AKT/mTOR pathway-related proteins was higher in ovarian cancer tissues than adjacent normal tissues. Lastly, expression of the ERS-related proteins Beclin 1, caspase-3 and LC3 II was higher in the sensitive group than the resistant group, while expression of Bcl-2, LC3 I, P62 and PI3K/AKT/mTOR pathway-related proteins was decreased. These results show that ERS promotes cell autophagy and apoptosis while reversing chemoresistance in ovarian cancer cells by inhibiting activation of the PI3K/AKT/mTOR signaling pathway. | Counterfeit |
Text : Cervical cancer has the second highest incidence rate among cancers in females, accounting for a majority of cancer-related deaths globally. However, the mechanism of cervical cancer pathogenesis is still unclear. UCA1 is considered an oncogene that can transcribe into a long noncoding RNA (lncRNA). This study aimed to determine the function of UCA1 in cervical cancer. A series of experiments involving BrdU, MTS, scratch-adhesion test, and cell invasion assays were conducted to determine the cellular capabilities of proliferation, viability, migration, and invasion, respectively. Binding sites between UCA1 and miR-143 were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. The results shown that the upregulation of lncRNA UCA1 was found in human cervical cancer. Interference of lncRNA UCA1 inhibited cell proliferation, migration, invasion, and viability. Results of the luciferase reporter assay revealed a binding site between lncRNA UCA1 and miR-206. Knockdown of lncRNA UCA1 could directly upregulate miR-206 expression. VEGF downregulation was also observed after knockdown of lncRNA UCA1. Moreover, co-transfection of anti-miR-206 oligodeoxyribonucleotide (AMO-206) in cervical cancer cells reversed the effect of lncRNA UCA1 on VEGF. Therefore, we concluded that LncRNA UCA1 is upregulated in cervical cancer, and its knockdown can upregulate miR-206, thus, suppressing the growth of cervical cancer cells. LncRNA UCA1 is a potential target in cervical cancer treatment. | Authentic |
Text : Non-coding circular RNAs (circRNAs) have displayed dysregulated expression in various tumor tissues. However, their role in the progression of cancers remains largely unknown. We aimed at examining the expression, functions, and molecular mechanisms of a new circRNA (circRNA_0023642) in gastric cancer (GC). We evaluated the expression levels of circRNA_0023642 in GC tissues, adjacent normal tissues and cells lines using qRT-PCR. The functional roles of circRNA_0023642 in GC were determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay, and flow cytometric analysis. Western blot was used to analyze the effect of circRNA_0023642 on the expression of EMT-related proteins. We found that circRNA_0023642 was upregulated in GC tissues and cell lines. Functionally, down-regulation of circRNA_0023642 displayed the tumor-inhibitory effects by suppressing cell proliferation, migration, and invasion as well as inducing apoptosis. Mechanically, our results revealed that the abnormal expression of circRNA_0023642 could influence the EMT signaling pathway, which was demonstrated by measuring the expression levels of N-cadherin, vimentin snail, and E-cadherin. Our findings suggest that circRNA_0023642 serves as a metastasis activator by promoting EMT and may represent a novel molecular therapeutic target for GC. | Authentic |
Text : Background: Hepatocellular carcinoma (HCC) is an aggressive primary hepatic cancer with high malignancy and poor prognosis. Long noncoding RNA HOTAIR has been classified as an oncogene to accelerate cell proliferation, migration, and invasion in many cancer types by interacting with the miRNA. Therefore, we assumed that HOTAIR might participate in HCC cell progression by interacting with miR-217-5p expression. Materials and Methods: The expression of HOTAIR and miR-217-5p in 35 HCC patients and HCC cells was measured by quantitative real-time polymerase chain reaction. Cell transfection was conducted using Lipofectamine 2000 transfection reagent. CCK8 and flow cytometry was applied for the measurement of cell proliferation and apoptosis. Cell migration and invasion capacities were carried out by transwell assay. Xenograft mice were constructed by subcutaneously injecting of stably transfected Huh-7 cells in mice. The interaction between HOTAIR and miR-217-5p was determined by luciferase reporter system. Protein expression of P13K, p-P13K, AKT, p-AKT, MMP-2, and MMP-9 was analyzed using Western blot assay. Results: The expression of HOTAIR was upregulated, whereas miR-217-5p was downregulated in HCC tumor tissues and cell lines (Hep3B and Huh-7) compared with normal tissues and human normal liver cell line MIHA. In addition, HOTAIR expression was negatively correlated with miR-217-5p expression in HCC (r2 = 0.1867, p = 0.0171). More importantly, HOTAIR knockdown induced apoptosis and inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). In vivo experiments revealed that the interference of HOTAIR inhibited tumor growth. Subsequently, luciferase reporter system confirmed the interaction between HOTAIR and miR-217-5p. The rescue experiments clarified that miR-217-5p inhibitor attenuated the suppression of HOTAIR silencing on HCC cell proliferation, migration, invasion, and EMT. Furthermore, miR-217-5p inhibitor restored the inhibition of HOTAIR silencing mediated p-PI3K/p-AKT/MMP-2/9 protein expression. Conclusions: HOTAIR contributes to cell progression in HCC by sponging miR-217-5p, representing promising biomarkers for HCC treatment. | Counterfeit |
Text : Liver kinase B1 (LKB1) is a newly discovered tumor suppressor gene that plays a role in apoptosis induction. However, the precise impact of LKB1 expression on gastric cancer (GC) progression and its correlation with survivin and p53 in GC have not yet been elucidated. The aim of this study was to explore the significance of LKB1 expression and its correlation with p53 and survivin in GC. In this study, LKB1 expression was detected in GC and adjacent paracancerous tissues from 150 patients through immunohistochemical (IHC) staining. The relationship between LKB1 expression and clinical pathological factors in GC was analyzed, alongside its correlation with p53 and survivin expression. LKB1 expression was reduced in GC tissues compared with adjacent paracancerous tissues (P=0.001). In patients with GC, lower LKB1 expression was associated with greater invasion depth (P=0.013), higher pTNM stage (P=0.009), and lymph node metastasis (P=0.029). Furthermore, LKB1 expression in GC was inversely associated with p53 (r=-0.181, P=0.027) and survivin expression (r=-0.198, P=0.015). Kaplan-Meier analysis indicated that the expression of LKB1, p53 and survivin, as well as tumor differentiation, invasion, and pTNM and lymph node metastasis were all associated with overall survival (OS) (all P<0.05). Finally, multivariate analysis showed that LKB1 expression [hazard ratio (HR): 0.605 (0.414-0.882), P=0.009], p53 expression [hazard ratio (HR): 1.840 (1.232-2.750), P=0.003], and survivin expression [hazard ratio (HR): 1.561 (1.039-2.345), P=0.032] were all independent prognostic factors for patients with GC. Our study suggests that LKB1 expression is reduced in GC, negatively correlated with p53 and survivin expression, and plays an important role in predicting invasion and metastasis of GC. | Authentic |
Text : This study aims to investigate the effect of microRNA-129 (miR-129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a normal group. Expression of miR-129, c-Fos, bax, and MAPK was detected by RT-qPCR and Western blotting. Hippocampal neurons were assigned into normal, blank, negative control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129 inhibitor+siRNA-c-Fos groups. The targeting relationship between miR-129 and c-Fos was predicted and verified by bioinformatics websites and dual-luciferase reporter gene assay. Cell proliferation after transfection was measured by MTT assay, and cell cycle and apoptosis by flow cytometry. c-Fos is a potential target gene of miR-129. Compared with the normal group, the other six groups showed a decreased miR-129 expression; increased expression of expression of c-Fos, Bax, and MAPK; decreased proliferation; accelerated apoptosis; more cells arrested in the G1 phase; and fewer cells arrested in the S phase. Compared with the blank and NC groups, the miR-129 mimic group and the siRNA-c-Fos group showed decreased expression of c-Fos, Bax, and MAPK, increased cells proliferation, and decreased cell apoptosis, fewer cells arrested in the G1 phase and more cells arrested in the S phase. However, the miR-129 inhibitor groups showed reverse consequences. This study suggests that miR-129 could inhibit the occurrence and development of epilepsy by repressing c-Fos expression through inhibiting the MAPK signaling pathway. | Counterfeit |
Text : Gamma ray can promote cancer cell apoptosis and cell cycle arrest. It is often used in the clinical treatment of tumors, including lung cancer. In this study, we aimed to explore the role of gamma ray treatment and its correlation with BTG2 in cell proliferation, apoptosis, and cell cycle arrest regulation in a lung cancer cell line. A549 cell viability, apoptosis rate, and cell cycle were investigated after gamma ray treatment. We then used siRNA for BTG2 to detect the effect of BTG2 knockdown on the progress of gamma ray-treated lung cancer cells. Finally, we investigated the signaling pathway by which gamma ray might regulate BTG2. We found that gamma ray inhibited A549 cell viability and promoted apoptosis and cell cycle arrest, while BTG2 knockdown could relieve the effect caused by gamma ray on A549 cells. Moreover, we confirmed that the effect of BTG2 partly depends on p53 expression and gamma ray-promoting BTG2 expression through the JNK/NF-κB signaling pathway. Our study assessed the possible mechanism of gamma ray in tumor treatment and also investigated the role of BTG2 in gamma ray therapy. All these findings might give a deep understanding of the effect of gamma ray on the progression of lung cancer involving BTG2. | Authentic |
Text : To assess the clinical efficacy of thoracoscopic lobectomy and segmentectomy in the treatment of patients with early-stage lung cancer. A total of 70 patients with early-stage non-small cell lung cancer who were treated in our hospital from April 2018 to May 2020 were recruited and assigned at a ratio of 1 : 1 to receive either segmentectomy (observation group) or lobectomy (control group). Outcome measures included clinical efficacy, surgery-related indicators, pulmonary function indicators (forced vital capacity (FVC) and forced expiratory volume in one second (FEV1)), postoperative complications, and recurrence and metastasis. There was no significant difference in the clinical efficacy between the two groups (P > 0.05). Segmentectomy was associated with a longer operation time and shorter hospital stay compared to lobectomy (P < 0.05). There was no statistical significance in the amount of intraoperative blood loss and the number of lymph nodes dissected (P > 0.05). Segmentectomy resulted in significantly higher FVC and FEV1 levels in patients compared to lobectomy (P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P > 0.05). The two groups of patients were followed up for 12 months after the operation, and there was no recurrence or metastasis in either group. The two surgical methods have similar efficacy and safety profiles, but for the treatment of patients with early-stage lung cancer, thoracoscopic segmentectomy is associated with a shorter hospital stay and better protection of the lung function of patients compared to lobectomy. | Authentic |
Text : Cervical cancer is a serious threat to women's health and is the third most common malignancy in women worldwide. Recent studies indicate that the long non-coding RNA CCAT1 plays a role in the malignant behavior of many tumors. However, the role of CCAT1 in cervical cancer is still unknown. Our aim is to evaluate the expression and investigate the regulatory role and potential mechanism of CCAT1 in cervical cancer. CCAT1 expression was measured by qRT-PCR. In addition, CCK-8 assays, colony formation assays, qRT-PCR assays, Transwell assays and xenograft experiments were performed to determine the role of CCAT1 in the proliferation and invasion in cervical cancer cells. The expression of CCAT1 in the cervical cancer tissues was higher than in the adjacent normal tissues. Overexpressing CCAT1 promoted cervical cancer cell proliferation, colony formation, and invasion in vitro. Elevated CCAT1 suppressed miR-181a expression, which was accompanied by an increased expression of MMP14 and HB-EGF. In contrast, knocking down CCAT1 resulted in increased expression of miR-181a, along with decreased expression of MMP14 and HB-EGF. Thus, CCAT1 is a key oncogenic lncRNA associated with cervical cancer and plays a role in promoting cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis. | Authentic |
Text : Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy is one of the most promising therapeutic strategies for the treatment of cholangiocarcinoma, which is the second most common hepatobiliary cancer. The aim of the present study was to evaluate the enhanced therapeutic effects of HSV-TK/GCV with gemcitabine on cholangiocarcinoma. QBC939 cholangiocarcinoma cells and mouse models of cholangiocarcinoma (established via tumor xenografts) received one of the following treatments: i) Gemcitabine therapy (3 µg/ml); ii) HSV-TK/GCV monotherapy; iii) HSV-TK/GCV + gemcitabine; and iv) control group, treated with phosphate-buffered saline. Cell proliferation was quantified using MTT assay and post-treatment tumor alterations were monitored using ultrasound imaging and optical imaging. For the in vitro experiments, the MTT assays demonstrated that the relative cell viabilities in the gene therapy, gemcitabine and gemcitabine + gene groups were 70.37±9.07, 52.64±8.28 and 34.21±6.63%, respectively. For the in vivo experiments, optical imaging indicated significantly decreased optical signals in the combination therapy group, as compared with the gemcitabine and gemcitabine + gene groups (1.68±0.74 vs. 2.27±0.58 and 2.87±0.82, respectively; Р<0.05). As demonstrated by ultrasound imaging, reduced tumor volumes were detected in the combination therapy group, as compared with the three control groups (114.32±17.17 vs. 159±23.74, 201.63±19.26 and 298.23±36.1 mm3, respectively; P<0.05). The results of the present study demonstrated that gemcitabine enhances the antitumoral effects of HSV-TK/GCV on cholangiocarcinoma, which may provide a novel therapeutic strategy for the management and treatment of cholangiocarcinoma using gemcitabine and gene therapy. | Authentic |
Text : In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein-protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease. | Authentic |