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Text : Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR. These results were replicated with several other human tumor types: BxPC3 (human pancreatic adenocarcinoma), MDA-MB-231 (human breast adenocarcinoma), M21 (human melanoma), and HeLa (human cervical adenocarcinoma). Development of an immunocompetent xenograft tumor model would allow the further elucidation of the interaction of the immune system with therapy in both preclinical research and patient derived xenografts. | Authentic |
Text : Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC. | Authentic |
Text : Conservative treatment for invasive bladder cancer (BC) involves a complete transurethral tumor resection combined with chemotherapy (CT) and radiotherapy (RT). The major obstacles of chemo-radiotherapy are the addition of the toxicities of RT and CT, and the recurrence due to RT and CT resistances. The flavonoid Silybin (Sb) inhibits pathways involved in cell survival and resistance mechanisms, therefore the purpose of this paper was to study in vitro and in vivo, the ability of Sb to improve the response to RT, in two murine BC cell lines, with different levels of invasiveness, placing emphasis on radio-sensitivity, and pathways involved in radio-resistance and survival. In vitro, Sb radio-sensitized murine invasive cells through the inhibition of RT-induced NF-κB and PI3K pathways, and the increase of oxidative stress, while non-invasive cells did not show to be sensitized. In vivo, Sb improved RT-response and overall survival in invasive murine tumors. As Sb is already being tested in clinical trials for other urological cancers and it improves RT-response in invasive BC, these results could have translational relevance, supporting further research. | Authentic |
Text : We report a non-covalent loading of ginsenoside compound K (CK) onto our previously reported gold nanoparticles (DCY51T-AuCKNps) through one-pot biosynthesis using a probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi. The ginsenoside-loaded gold nanoparticles were characterized by various analytical and spectroscopic techniques such as field emission transmission electron microscopy (FE-TEM), energy-dispersive X-ray (EDX) spectroscopy, elemental mapping, X-ray powder diffraction (XRD), selected area electron diffraction (SAED), Fourier-transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS). Furthermore, drug loading was also determined by liquid chromatography-mass spectrometry (LC-MS). In addition, DCY51T-AuNps and DCY51T-AuCKNps were resistant to aggregation caused by pH variation or a high ionic strength environment. Cell-based study confirmed that DCY51T-AuCKNps exhibited slightly higher cytotoxicity compared to ginsenoside CK treatment in A549 cells (human lung adenocarcinoma cell line) and HT29 (human colorectal adenocarcinoma cell line). Upon laser treatment, DCY51T-AuCKNps showed enhanced cell apoptosis in A549, HT29 and AGS cells (human stomach gastric adenocarcinoma cell line) compared with only DCY51T-AuCKNps treated cells. In conclusion, this preliminary study identified that DCY51T-AuCKNps act as a potent photothermal therapy agents with synergistic chemotherapeutic effects for the treatment of cancer. | Authentic |
Text : The aim of this study was to investigate the potential effects of microRNA-135b-5p (miR-135b) on the development of malignant melanoma (MM) and the relevant mechanism. The expression level of miR-135b in MM tissues and cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Online prediction software and luciferase reporter assays were used to predict and verify the possible target of miR-135b, respectively. Furthermore, the effects of the miR-135b on MM A375 cells were determined by Western blotting, MTT, and transwell assays. MiR-135b was significantly down-regulated in MM. RING-box protein 1 (RBX1) was verified as a direct target of miR-135b. Subsequent experiments showed that down-regulation of RBX1 resulted from miR-135b up-regulation could significantly inhibit the proliferation, invasion, and migration abilities of MM cells. MiR-135b inhibited the progression of MM by targeting RBX1. Our findings revealed that miR-135b/RBX1 might be a potential therapeutic target for the treatment of MM. | Authentic |
Text : Recent studies have revealed that long noncoding RNAs (lncRNAs) play important roles in the progression of tumorigenesis. Oral squamous cell carcinoma is a disease widely widespread all over the world. The aim of this study was to identify how lncRNA INHBA-AS1 functions in the progression of OSCC. LncRNA INHBA-AS1 expression in both OSCC cells and 48 paired tissue samples was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The function of INHBA-AS1 was identified by the transwell assay, wound healing assay, and proliferation assay in vitro. Meanwhile, the role of INHBA-AS1 was investigated through tumor formation assay in vivo. Furthermore, the underlying mechanism was explored by the luciferase assays and RNA immunoprecipitation assay (RIP). INHBA-AS1 was highly expressed in OSCC tissues when compared with adjacent tissue samples. The proliferation, invasion, and migration of OSCC cells were significantly inhibited after the knockdown of INHBA-AS1 in vitro. Meanwhile, the knockdown of INHBA-AS1 remarkably inhibited tumor growth and metastasis in vivo. Besides, miR-143-3p was down-regulated after the knockdown of INHBA-AS1 in vitro. The expression of miR-143-3p was negatively correlated with the expression of INHBA-AS1 in OSCC tissues. In addition, miR-143-3p was directly targeted by INHBA-AS1. The knockdown of INHBA-AS1 repressed cell migration, invasion, and proliferation in OSCC by sponging miR-143-3p, which might offer a new therapeutic intervention for OSCC patients. | Counterfeit |
Text : As a member of the miRNA family, let-7c has been identified as a tumor suppressor in many cancers. However, the molecular biological function of let-7c in glioma has not been elucidated. The aim of this study was to explore let-7c expression levels and evaluate its function in glioma cells. We first measured the expression of let-7c in four glioma cell lines and a normal cell line by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and the results showed that let-7c was downregulated in glioma cells. By applying gain-of-function and loss-of-function assays, the experiments suggested that dysregulation of let-7c could obviously affect cell proliferation, metastasis, and invasion. Based on online bioinformatics analysis and Dual-Luciferase Reporter assays, we found that E2F5 was a target gene of let-7c and contributed to the function of let-7c in glioma cells. Our investigations indicated that loss of let-7c contributed to the progression of glioma cells. | Authentic |
Text : Oral cancer being one of the lethal cancers is generally detected at advanced stages and causes significant mortality world over. The unavailability of the reliable biomarkers and therapeutic targets/agents forms a bottleneck in the treatment of oral cancer. MicroRNAs are considered of immense therapeutic potential for the treatment of cancer. Consistently, in this study the role and therapeutic potential of miR-650 was explored in oral cancer. The analysis of miR-650 expression by qRT-PCR revealed significant (p < 0.05) upregulation of miR-650 in oral cancer cell lines. Cell cycle analysis by flow cytometery revealed that suppression of miR-650 significantly (p < 0.05) inhibits the proliferation of the SCC-25 cells by prompting Sub-G1 cell cycle arrest. Further, miR-650 suppression also inhibited the migration and invasion of the SCC-25 oral cancer cells as revealed by transwell assays. TargetScan analysis showed that miR-650 targets Growth factor independent 1 (Gfi1). Moreover, the results of western blot analysis showed that miR-650 suppression inhibits the expression of Gfi1. Interestingly, suppression of Gfi1 exhibited similar effects on cell proliferation, migration and invasion of the oral cancer cells as that of miR-650 suppression. Nonetheless, miR-650 promoted the proliferation, migration and invasion of the SCC-25 cells by upregulating the expression of Gfi1. Moreover, overexpression of miR-650 could not rescue the effects of Gfi1 silencing on SCC-25 oral cancer cells. Conversely, overexpression of Gfi1 could rescue the effects of miR-650 inhibition on SCC-25 cell proliferation, migration and invasion. Additionally, miR-650 suppression could also inhibit the xenografted tumor growth in vivo by inhibiting the expression of Gfi1. Taken together, miR-650 may prove to be an important therapeutic target for the management of oral cancers. | Counterfeit |
Text : Rhus verniciflua Stokes has been widely used as a traditional medicinal plant with a variety of pharmacological activities. We investigated the mechanisms involved in mediating the effects of Rhus verniciflua Strokes (R. verniciflua) extract in human chronic myelogenous leukemia K562 cells, including caspase-dependent apoptotic pathways related to cell-cycle arrest, as well as the inhibition of nuclear factor NF-κB activation and upregulation of the mitogen-activated protein kinase (MAPK) signaling pathway. R. verniciflua extract suppressed the abnormal cellular proliferation of K562 cells in a dose- and time‑dependent manner and increased the quantitative proportions of cells involved in the early and late process of apoptosis. Furthermore, R. verniciflua extract significantly mediated the mRNA levels of pro-apoptotic and anti-apoptotic regulators, such as Bcl-2, Bax, Mcl-1 and survivin in apoptotic cells. Particularly, the treatment of K562 cells with R. verniciflua extract augmented the caspase‑3 activity and increased the expression of caspase‑3 protein, while co-treatment with R. verniciflua extract and the permeant pan‑caspase inhibitor Z-VAD-FMK and caspase‑3 inhibitor Z-DEVD-FMK inversely enhanced the proliferation of K562 cells. The extract of R. verniciflua inhibited the activation of NF-κB and the phosphorylation of ERK. Collectively, these results indicated that the extract of R. verniciflua inhibited the proliferation of human chronic myelogenous leukemia K562 cells by activating the apoptotic process via caspase‑3 overexpression and the regulation of the NF-κB and MAPK signaling. | Authentic |
Text : Pancreatic adenocarcinoma (PAAD) a highly lethal malignancy. The current use of clinical parameters may not accurately predict the clinical outcome, which further renders the unsatisfactory therapeutic outcome. In this study, we retrospectively analyzed the clinical-pathological characteristics and prognosis of 253 PAAD patients. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted to assess risk factors and clinical outcomes. For functional study, we performed bidirectional genetic manipulation of lactate dehydrogenase A (LDHA) in PAAD cell lines to measure PAAD progression by both in vitro and in vivo assays. LDHA is particularly overexpressed in PAAD tissues and elevated serum LDHA-transcribed isoenzymes-5 (LDH-5) was associated with poorer patients' clinical outcomes. Genetic overexpression of LDHA promoted the proliferation and invasion in vitro, and tumor growth and metastasis in vivo in murine PAAD orthotopic models, while knockdown of LDHA exhibited opposite effects. LDHA-induced L-lactate production was responsible for the LDHA-facilitated PAAD progression. Mechanistically, LDHA overexpression reduced the phosphorylation of metabolic regulator AMPK and promoted the downstream mTOR phosphorylation in PAAD cells. Inhibition of mTOR repressed the LDHA-induced proliferation and invasion. A natural product berberine was selected as functional inhibitor of LDHA, which reduced activity and expression of the protein in PAAD cells. Berberine inhibited PAAD cells proliferation and invasion in vitro, and suppressed tumor progression in vivo. The restoration of LDHA attenuated the suppressive effect of berberine on PAAD. Our findings suggest that LDHA may be a novel biomarker and potential therapeutic target of human PAAD. | Authentic |
Text : Extensive investigations into long noncoding RNAs (lncRNAs) in various diseases and cancers, including acute myocardial infarction (AMI) have been conducted. The current study aimed to investigate the role of lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) in myocardial damage by targeting solute carrier family 8 member A1 (SLC8A1) via cyclic guanosine 3',5'-monophosphate-protein kinase G (cGMP-PKG) signaling pathway in AMI mouse models. Differentially expressed lncRNA in AMI were initially screened and target relationship between lncRNA SLC8A1-AS1 and SLC8A1 was then verified. Infarct size, levels of inflammatory factors, biochemical indicators, and the positive expression of the SLC8A1 protein in AMI were subsequently determined. The expression of SLC8A1-AS1, SLC8A1, PKG1, PKG2, atrial natriuretic peptide, and brain natriuretic peptide was detected to assess the effect of SLC8A1-AS1 on SLC8A1 and cGMP-PKG. The respective contents of superoxide dismutase, lactate dehydrogenase (LDH), and malondialdehyde (MDA) were detected accordingly. Microarray data GSE66360 provided evidence indicating that SLC8A1-AS1 was poorly expressed in AMI. SLC8A1 was verified to be a target gene of lncRNA SLC8A1-AS1. SLC8A1-AS1 upregulation decreased levels of left ventricular end-systolic diameter, -dp/ dt max , interleukin 1β (IL-1β), IL-6, transforming growth factor α, nitric oxide, inducible nitric-oxide synthase, endothelial nitric-oxide synthase, infarct size, LDH activity and MDA content, and increased IL-10, left ventricular end-diastolic pressure and + dp/ dt max . Furthermore, the overexpression of SLC8A1-AS1 was noted to elicit an inhibitory effect on the cGMP-PKG signaling pathway via SLC8A1. In conclusion, lncRNA SLC8A1-AS1, by downregulating SLC8A1 and activating the cGMP-PKG signaling pathway, was observed to alleviate myocardial damage, inhibit the release of proinflammatory factors and reduce infarct size, ultimately protecting against myocardial damage. | Counterfeit |
Text : Studies have found that miR-665 acted as a tumor suppressor or an oncogene in different malignancies. miR-665 expression was elevated in gastric adenocarcinoma tissues; however, its role and mechanism in this disease are not fully clarified. The expression of miR-665 and its target gene was detected in human gastric adenocarcinoma tissues and cells. Moreover, we analyzed the effects of miR-665 on the proliferation, migration, and epithelial-mesenchymal transition (EMT) of gastric adenocarcinoma cells as well as tumor growth in vivo. The mechanisms of miR-665 in gastric adenocarcinoma were investigated by using molecular biology techniques. We found miR-665 was upregulated and suppressor of cytokine signaling 3 (SOCS3) was downregulated in gastric adenocarcinoma tissues and cells. Elevated miR-665 was positively correlated with tumor size, lymph node metastasis, invasion depth, TNM stage, and poor differentiation in gastric adenocarcinoma patients. Overexpression of miR-665 promoted, whereas knockdown of miR-665 suppressed the proliferation, migration, and EMT of gastric adenocarcinoma cells. Furthermore, we demonstrated that miR-665 functioned through targeting SOCS3, followed by activation of the FAK/Src signaling pathway in gastric adenocarcinoma cells. miR-665 antagomir inhibited tumor growth as well as the activation of the FAK/Src pathway but increased SOCS3 expression in nude mice. In addition, miR-665 expression was negatively regulated by long noncoding RNA maternally expressed gene 3 (MEG3). In conclusion, miR-665 acted as an oncogene in gastric adenocarcinoma by inhibiting SOCS3 followed by activation of the FAK/Src pathway and it was negatively modulated by MEG3. miR-665 may be a promising therapeutic target for the treatment of gastric adenocarcinoma. | Authentic |
Text : MicroRNAs (miRNAs) are increasingly recognized as important therapeutic targets in cancer. Here we aim to investigate the role of miR-198, a broad-spectrum tumor suppressor, in gastric cancer (GC). MiR-198 overexpression was achieved by transfection of miR-198 mimics, followed by evaluation of cell viability using cell-counting kit 8. Cell cycle arrest and apoptosis were assessed by Annexin-V-FITC/Propidium Iodide (PI) staining flow cytometry respectively. The target of miR-198 was identified by bioinformatical analysis and confirmed by dual-luciferase assay, along with real-time PCR and Western blot analyses of target gene expression after transfection of miR-198 mimics. GC tissues were characterized by miR-198 down-regulation. Restoration of miR-198 expression attenuated GC cell proliferation and colony formation, meanwhile inducing significant G0/G1 arrest. Furthermore, combinatory therapy of cisplatin and miR-198 induced greater anti-tumor effects than treatment with cisplatin single therapy. We also identified fibroblast growth factor receptor 1 (FGFR1) as a direct target gene of miR-198. Furthermore, FGFR1 silencing elicited a similar tumor-suppressive effect as miR-198 overexpression. FGFR1 overexpression antagonized the anti-tumor effects of miR-198 overexpression. MiR-198/FGFR1 axis plays an important role in proliferation and apoptosis of GC. Therapies targeted to miR-198 can potentially improve GC treatment. | Authentic |
Text : Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor (TKI), has been approved for HER2-positive breast cancer patients. Nevertheless, its inhibitory effect on EGFR did not deliver clinical benefits for triple-negative breast cancer (TNBC) patients even EGFR overexpression was frequently found in this disease. Moreover, lapatinib was unexpectedly found to enhance metastasis of TNBC cells, but the underlying mechanisms are not fully understood. In this study, we explored that the level of interleukin-6 (IL-6) was elevated in lapatinib-treated TNBC cells. Treatment with IL-6 antibody abolished the lapatinib-induced migration. Mechanistically, the signaling axis of Raf-1/mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinases (JNKs), p38 MAPK, and activator protein 1 (AP-1) was activated in response to lapatinib treatment to induce IL-6 expression. Furthermore, our data showed that microRNA-7 directly binds and inhibits Raf-1 3'UTR activity, and that down-regulation of miR-7 by lapatinib contributes to the activation of Raf-1 signaling pathway and the induction of IL-6 expression. Our results not only revealed IL-6 as a key regulator of lapatinib-induced metastasis, but also explored the requirement of miR7/Raf-1/MAPK/AP-1 axis in lapatinib-induced IL-6 expression. | Authentic |
Text : In the present study, we aimed to uncover the potential functions of circular RNA (circRNA) pleckstrin and Sec7 domain containing 3 (circ_PSD3) in papillary thyroid carcinoma (PTC) development. The abundance of circ_PSD3, PSD3 messenger RNA (mRNA), microRNA-637 (miR-637) and hemogen (HEMGN; EDAG-1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was employed to measure cell cycle progression and cell apoptosis. Western blot assay was used to examine protein expression. The proliferation ability and motility of PTC cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays, respectively. The interaction between miR-637 and circ_PSD3 or HEMGN was tested by dual-luciferase reporter assay. Animal experiments were used to explore the role of circ_PSD3 in PTC progression in vivo. Circ_PSD3 was aberrantly up-regulated in PTC tumor tissues compared with adjacent normal tissues. Circ_PSD3 and HEMGN promoted the cell cycle progression, proliferation and metastasis and impeded the apoptosis of PTC cells. MiR-637 was a direct target of circ_PSD3, and miR-637 directly interacted with HEMGN mRNA in PTC cells. Circ_PSD3 silencing-induced effects in PTC cells were partly attenuated by the addition of anti-miR-637 or HEMGN overexpression plasmid. Circ_PSD3/miR-637/HEMGN regulated the activity of PI3K/Akt signal pathway in PTC cells. Circ_PSD3 silencing inhibited the tumor growth in vivo. Circ_PSD3 promoted the progression of PTC through regulating miR-637/HEMGN axis and activating PI3K/Akt signaling. Circ_PSD3/miR-637/HEMGN signaling axis might be a potential target for PTC therapy. | Authentic |
Text : Tumour-associated macrophage (TAM) is an important component in tumour microenvironment. Generally, TAM exhibits the function of M2-like macrophage, which was closely related to angiogenesis and tumour progression. Dioscin, a natural steroidal saponin, has shown its powerful anti-tumour activity recently. However, the mechanism of dioscin involved in immune regulation is still obscure. Here, we observed dioscin induced macrophage M2-to-M1 phenotype transition in vitro and inhibited IL-10 secretion. Meanwhile, the phagocytosis of macrophages was enhanced. In subcutaneous lung tumour models, dioscin inhibited the augmentation of M2 macrophage populations. Furthermore, dioscin down-regulated STAT3 and JNK signalling pathways in macrophages in vitro. In BMDMs, activating JNK and inhibiting STAT3 induce macrophages to M1 polarization while inhibiting JNK and activating STAT3 to M2 polarization. Additionally, condition mediums from dioscin-pre-treated macrophages inhibited the migration of 3LL cells and the tube-formation capacity of HUVECs. What's more, dioscin-mediated macrophage polarization inhibited the in vivo metastasis of 3LL cells. In conclusion, dioscin may act as a new anti-tumour agent by inhibiting TAMs via JNK and STAT3 pathways in lung cancer. | Authentic |
Text : The aim of this study was to investigate the expression and clinical significance of hPTTG1 in gastric cancer. Immunohistochemistry was performed to determine the expression of hPTTG1 in gastric cancer tissues. Results showed that the positive expression of hPTTG1 in gastric cancer tissues was 60.00%, while in adjacent normal tissues it was 17.78%. The expression of hPTTG1 was correlated with differentiation levels, clinical classification and lymph node metastasis, but did not correlate with gender, age or pathological types. hPTTG1 was, therefore, overexpressed in gastric cancer tissues. The progression of gastric cancer was found to be correlated with the upregulation of the expression of hPTTG1. hPTTG1 detection may be helpful in evaluating the ability of the clinical classification and lymph node metastasis in gastric cancer to predict outcomes. These factors act as indicators of the biological behavior of gastric cancer and are fairly good markers for prognosis and therapy. | Authentic |
Text : Paclitaxel‑based chemotherapy is a promising approach for prostate cancer treatment. However, single‑drug chemotherapy is associated with an increased risk of drug resistance. Therefore, novel combination chemotherapy regimens are a popular topic of research. Zinc participates in the regulation of apoptosis, for example in the form of Zn2+ and via zinc‑dependent enzymes. Zinc can either induce or suppress apoptosis, and its effect depends primarily on its concentration. Previous research has demonstrated that physiological concentrations of zinc can directly induce apoptosis of PC‑3 prostate cancer cells via the mitochondrial pathway. In prostate cancer tissues, zinc concentrations have been demonstrated to be reduced compared with non-cancerous tissues. Furthermore, the concentration of zinc has been demonstrated to decrease further with cancer progression. In the present study, it was investigated whether exposure of PC‑3 cells to zinc improved their sensitivity to the chemotherapeutic agent, paclitaxel. MTT assays, cell clone formation assays, Hoechst staining and flow cytometry revealed that zinc enhanced PC‑3‑cell chemosensitivity to paclitaxel. Western blotting and reverse transcription‑polymerase chain reaction were used to determine that the mitochondria‑mediated apoptosis signaling pathway is involved with zinc/paclitaxel‑induced cell death. The present study provides a foundation for the development of novel tumor combination therapy. | Authentic |
Text : Cachexia is a multifactorial inflammatory syndrome with high prevalence in cancer patients. It is characterized by a metabolic chaos culminating in drastic reduction in body weight, mainly due to skeletal muscle and fat depletion. Currently, there is not a standard intervention for cachexia, but it is believed that a dynamic approach should be applied early in the course of the disease to maintain or slow the loss of physical function. The present review sought to explain the different clinical and experimental applications of different models of exercise and their contribution to a better prognosis of the disease. Here the advances in knowledge about the application of physical training in experimental models are elucidated, tests that contribute substantially to elucidate the cellular and biochemical mechanisms of exercise in different ways, as well as clinical trials that present not only the impacts of exercise in front cachexia but also the challenges of its application in clinical practice. | Authentic |
Text : Recently, circular RNA was reported to be a significant participant in the development of tumorigenesis, including colorectal cancer. Therefore, we aimed to clarify the precise role of circ-keratin 6C (circ-KRT6C) in colorectal cancer progression. The relative expression levels of circ-KRT6C, microRNA-485-3p (miR-485-3p), and programmed cell death receptor ligand 1 (PDL1) were analyzed by real-time quantitative polymerase chain reaction and Western blot assays. The proliferation was assessed by cell count kit 8 and colony-forming assays. The apoptotic cells were determined by flow cytometry assay. The migration and invasion were analyzed by transwell assay. Colorectal cancer cells were cocultured with peripheral blood mononuclear cells or cytokine-induced killer cells to assess immune response. The interaction relationships among circ-KRT6C, miR-485-3p, and PDL1 were examined by dual-luciferase reporter assay. The effects of circ-KRT6C inhibition in vivo were analyzed by an animal experiment. circ-KRT6C was overexpressed in colorectal cancer tissues and cells, and its level was associated with overall survival time of patients with colorectal cancer. The suppression of circ-KRT6C suppressed growth, migration, invasion, and immune escape while stimulating apoptosis in colorectal cancer cells, which was abolished by shortage of miR-485-3p. In addition, overexpression of miR-485-3p repressed malignant progression and immune evasion of colorectal cancer by targeting PDL1, implying that PDL1 was a functional target of miR-485-3p. A xenograft experiment also suggested that circ-KRT6C inhibition could repress tumor growth in vivo. circ-KRT6C could increase PDL1 expression by functioning as an miR-485-3p sponge, which promoted malignant progression and immune evasion of colorectal cancer cells. SIGNIFICANCE STATEMENT: circ-keratin 6c could increase programmed cell death receptor ligand 1 expression by functioning as a microRNA-16-5p sponge, which promoted malignant progression and immune evasion of colorectal cancer. | Authentic |
Text : Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with a high mortality rate and poor prognosis. In this research, we investigated the exact role of long non-coding ribonucleic acids (lncRNA) MNX1-AS1 in the metastasis of ESCC and its possible mechanism. To investigate the functions of MNX1-AS1 in ESCC, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to detect MNX1-AS1 expression of ESCC tissues and cells. Besides, functional assays, including transwell assay and wound healing assay, were performed. Furthermore, qRT-PCR and Western blot assay were used to explore the possible underlying regulatory mechanism. The expression level of MNX1-AS1 was significantly increased in both ESCC tissues sample and cells. Moreover, knockdown of MNX1-AS1 markedly inhibited the migration and invasion of ESCC cells. Besides, knockdown of MNX1-AS1 remarkably down-regulated the mRNA and protein levels of insulin-like growth factor 2 (IGF2). Furthermore, IGF2 expression was positively correlated with MNX1-AS1 expression in ESCC tissues. MNX1-AS1 serves as a potential oncogene in ESCC, which can significantly promote ESCC cell migration and invasion by up-regulating IGF2. Our findings may provide a new therapeutic target of ESCC. | Authentic |
Text : The objective of this study was to investigate the effects of ultrasound-guided injection of ultrasound contrast agents (UCAs) and the p53 gene on the treatment of rats with breast cancer (BC). Assembly of the p53 expression vector as well as that of a rat model with BC consisted of 200 successfully modeled rats randomly divided into 5 groups: p53 gene introduction, p53 gene introduction + ultrasound irradiation, p53 gene introduction + UCAs, p53 gene introduction + UCA + ultrasound irradiation, and UCA + ultrasound irradiation groups. Expression of p53 was detected via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining. In the p53 gene introduction + ultrasound irradiation group, we observed increased tumor volume with blood flow signals around and necrotic tumor tissues with an inhibition rate of 36.30%, as well as higher expression of p53 than that in the p53 gene introduction group and p53 gene introduction + UCA group. In the p53 gene introduction + UCA + ultrasound irradiation group, tumor volume increased slightly with reduced blood flow signals and massive degenerative necrosis of tumor cells was identified with inhibition rate of 62.62%, and expression of p53 was higher than that in the rest groups. Taken together, the key findings obtained from the present study elucidate that injection of p53 gene and UCA microbubbles guided by ultrasound could increase the expression of p53, thus inhibiting the tumor growth in rats with BC. | Authentic |
Text : The repair of peripheral facial paralysis is a long-term problem in neurosurgery, and nerve repair is often needed. Due to the high differentiation of nerve tissue and the slow regeneration of peripheral nerve fibers, the repair effect after peripheral nerve injury is not ideal. In recent years, studies have found that the inflammatory response after peripheral nerve injury also has an important impact on the repair of peripheral nerve defects. This study depends on the utilization of traditional needle therapy in the treatment of fringe facial loss of motion, and the clinical adequacy of needle therapy in addition to nerve fix in the intense period of fringe facial loss of motion was seen with an electron magnifying lens. Endeavor to give significant exploration results to the clinical treatment of fringe facial loss of motion gives a straightforward, simple, protected, and successful new treatment innovation for the clinical treatment of the infection and enriches the treatment plan for peripheral facial paralysis. Transmission electron microscopy observations showed that 21 days after the artificial nerve was repaired, the nerve injury showed different degrees of recovery, and the myelin sheath was forming and gradually wrapping the new axons, which was similar to the catheter group (NC) and hydrogel group (HC). In contrast, the myelin layer of the fibroblast group (FHC) is more obvious, and the repair effect is better. In the maintenance of fringe nerve surrenders, irritation is an unavoidable interaction, and moderate needle therapy is useful to advance the maintenance of fringe nerve abandons. Talking about the law of nerve fix reaction in fringe nerve imperfection fix is helpful to the examination of fringe nerve deformity fix. Tests have shown that utilizing needle therapy and moxibustion joined with nerve fixes has accomplished great outcomes in the treatment of fringe facial loss of motion, and the patient's recuperation rate has expanded by over 30%. | Counterfeit |
Text : It has been shown that nuclear expression of S100A4 is significantly correlated with increased metastasis and reduced survival in patients with gastric cancer and many other cancers. However, the factors which could influence the nuclear contents of S100A4 in cancer cells are not clear. It has also been reported that Interleukin-1β (IL-1β) promotes the nuclear translocation of S100A4 in chondrocytes. Previous studies have shown that IL-1β promotes the stemness of colon cancer cells, and S100A4 is also involved in maintaining cancer-initiating cells in head and neck cancers. We speculate that IL-1β might promote the nuclear translocation of S100A4 protein in MGC803 gastric cancer cells and therefore enhance their stem-like properties. The results from Western-blot and qRT-PCR analysis showed that IL-1β increased the nuclear and total cellular content of S100A4 protein and S100A4 mRNA level in MGC803 cells. LY294002, a pharmacological inhibitor of Phosphoinositide 3-kinase (PI3K) reversed the above effects. Functional studies indicated that IL-1β promoted the colony-forming and spheroid-forming capabilities of the cells and the expression of SOX2 and NANOG gene. PI3K or S100A4 inhibition reversed the IL-1β-mediated increase in colony and spheroid-forming capabilities of the cells. LY294002 also reversed the elevated SOX2 and NANOG expression induced by IL-1β. Our study demonstrated that IL-1β promote the nuclear translocation of S100A4 protein in gastric cancer cells MGC803, which are PI3K dependent, suggesting the existence of IL-1β-PI3K-S100A4 pathway for the first time. The study also showed that IL-1β promoted stem-like properties of the cells through the new pathway. | Authentic |
Text : Transurethral resection of bladder tumors (TURBT) is the main surgical treatment for bladder cancer, but during TURBT, it is easy to stimulate the obturator nerve passing close to the lateral side of the bladder wall and induce involuntary contraction of the adductor muscle group of the thigh innervated by it, which will affect the surgical process and lead to adverse reactions. Obturator nerve block (ONB) helps to prevent the obturator nerve reflex. This study systematically evaluated and meta-analyzed the reports on the co-application of ONB and spinal anesthesia (SA) in TURBT in recent years to provide evidence for clinical diagnosis and treatment. The clinical randomized controlled literature studies of ONB combined with SA in TURBT published in PubMed, EMBASE, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang databases from January 2000 to December 2021 were searched. After screening the qualified literature studies, the literature quality was assessed by the Jadad scale. The incidence of obturator nerve reflex, the incidence of bladder perforation, length of hospital stay, and tumor recurrence rate were used as outcome indicators. The meta-analysis was performed with the R language toolkit. A total of 444 articles were initially retrieved, and after the screening, a total of 8 articles were included in the selection, and a total of 635 patients with ureterovesical tumor resection were included. The meta-analysis showed that the use of SA + ONB anesthesia during TURBT was associated with a smaller incidence of bladder perforation (RR = 0.24, 95% CI (0.11, 0.53), Z = -3.48, P=0.0005), a smaller incidence of obturator nerve reflex (RR = 0.22, 95% CI (0.13, 0.36), Z = -6.11, P=0.0001), a significantly shorter length of hospital stay (MD = -1.81, 95% CI (-2.65, -0.97), Z = -4.24, P=0.0001), and a significantly lower tumor recurrence rate (RR = 0.46, 95% CI (0.29, 0.73), Z = -3.30, P=0.001) compared with SA alone. The application of SA combined with ONB in TURBT can effectively reduce the incidence of obturator nerve reflex, reduce the incidence of bladder perforation, shorten the hospital stay and reduce the tumor recurrence rate. | Authentic |
Text : Recent studies have demonstrated that microRNAs regulate gene expression and are related to cancer progression. Increasing evidence shows that miR-618 plays an important role in a variety of tumors, including thyroid carcinomas, breast cancer and lymphoma cancer. However, no studies have examined the expression or function of miR-618 in gastric cancer (GC). In this study, we examined the effects and molecular mechanisms of miR-618 in GC. We compared the expression levels of miR-618 in 90 paired GC tissues and adjacent noncancerous tissues. Cell cycle, apoptosis and transwell assays were performed in GC cells with miR-618 mimic or inhibitor in vitro. We first used quantitative PCR(qPCR) to show that miR-618 expression levels were downregulated in GC tissues, which showed statistical significance. Next we used transwell assays to prove that miR-618 suppressed the invasion and migration capacity of GC cells. Furthermore, screening of the miRDB and Target Scan Human databases indicated TGF-β2 as a downstream target of miR-618. In further research, we identified TGF-β2 as a target gene of miR-618 by the luciferase reporter assay. Western blot analysis confirmed that TGF-β2 expression was inversely correlated with miR-618 expression. In situ hybridization showed that miR-618 expression level was downregulated in GC tissues. In conclusion, our findings suggest that miR-618 may function as a tumor suppressor in GC and suppresses metastasis in GC by negatively regulating the transcriptional level of TGF-β2. Anat Rec, 302:931-940, 2019. © 2019 Wiley Periodicals, Inc. | Authentic |
Text : N6-Methyladenosine (m6A) is the most common posttranscriptional modification of RNA and plays critical roles in cancer pathogenesis. However, the biological function of long noncoding RNA (lncRNA) methylation remains unclear. As a demethylase, ALKBH5 (alkylation repair homolog protein 5) is involved in mediating methylation reversal. The purpose of this study was to investigate lncRNA m6A modification and its role in gastric cancer (GC). Bioinformatics predicted interactions of ALKBH5 with lncRNAs. Five methods were employed to assess the function of nuclear paraspeckle assembly transcript 1 (NEAT1), including gene silencing, RT-PCR, separation of nuclear and cytoplasmic fractions, scrape motility assays, and transwell migration assays. Then, m6A RNA immunoprecipitation and immunofluorescence were used to detect methylated NEAT1 in GC cells. Rescue assays were performed to define the relationship between NEAT1 and ALKBH5. NEAT1 is a potential binding lncRNA of ALKBH5. NEAT1 was overexpressed in GC cells and tissue. Additional experiments confirmed that knockdown of NEAT1 significantly repressed invasion and metastasis of GC cells. ALKBH5 affected the m6A level of NEAT1. The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects GC invasion and metastasis. Our findings indicate a novel mechanism by which ALKBH5 promotes GC invasion and metastasis by demethylating the lncRNA NEAT1. They may be potential therapeutic targets for GC. | Authentic |
Text : Melanoma is one of the most aggressive and life-threatening skin cancers, and in this research, we aimed to explore the functional role of circular RNA VANGL1 (circVANGL1) in melanoma progression. The expression levels of circVANGL1 were observed to be significantly increased in clinical melanoma tissues and cell lines. Moreover, circVANGL1 knockdown suppressed, while circVANGL1 overexpression promoted the proliferation, migration and invasion abilities of melanoma cells. Further investigations confirmed the direct binding relation between circVANGL1 and miR-150-5p in melanoma, and restoration of miR-150-5p blocked the effects of circVANGL1 overexpression in melanoma cells. We further found that circVANGL1 was up-regulated by TGF-β treatment, and the enhanced EMT of TGF-β-treated melanoma cells was blocked by circVANGL1 knockdown. In conclusion, these results indicated that circVANGL1 might serve as a promising therapeutic target for melanoma. | Authentic |
Text : We aimed to understand whether metformin imposes the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway. Luciferase assay, RT-PCR, and Western-blot, MTT and flow cytometry analysis were performed to understand and the mechanism, by which metformin enhance the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway. HBX promoted viability of three types of cell lines, while metformin inhibited apoptosis of above two cells. ZEB1 was a direct downstream of miR-200a, which was further confirmed that miR-200a reduced luciferase activity of wild-type but not mutant ZEB1 3'UTR, and HULC was bound to region of miR-200a-3p using alignment prediction, but can't affect ZEB1 level. HULC transcription ability, HULC, ZEB1, and p18 levels were much higher in cell treated with HBX, while notably lower in cell treated with metformin, furthermore miR-200a level in cell showed an opposite trend as HULC, ZEB1, and p18 levels. HULC siRNA and miR-200a had no effect on HULC transcription ability, but decreased HULC, ZEB1, and p18 levels, and increased miR-200a expression. HBV (+) HCC +metformin exhibited a higher survival ratio and a lower recurrence rates than HBV (+) HCC group, HBV (-) HCC displayed an even higher survival ratio and an even lower recurrence rates than HBV (+) HCC + metformin groups. This study indicated that metformin imposed inhibitory effect on the HBV-associated HCC by negatively regulating the HULC/p18/miR-200a/ZEB1 signaling pathway. | Authentic |
Text : Circular RNAs (circRNAs) which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process. However, the expression profile and molecular mechanism of circRNA ATXN7 (circATXN7) is still mostly uncertain in gastric cancer (GC). qRT-PCR analysis was performed to detect the expression of circATXN7, miR-4319 and ENTPD4 in GC tissues and cells. CCK-8, colony formation, EdU, flow cytometry, TUNEL and transwell assays were conducted to assess the effect of circATXN7 or miR-4319 on cell proliferation, apoptosis and invasion. In vivo assays were utilized to further analyze the function of circATXN7 on the tumorigenesis and progression of GC. The interaction between miR-4319 and circATXN7 (or ENTPD4) was verified using luciferase reporter and RNA pull-down assays. The results showed an upregulated circATXN7 expression in GC tissues and cell lines. Besides, silenced circATXN7 hampered the proliferation and invasion as well as promoted the apoptosis in GC cells. Moreover, low expression of miR-4319 was found in GC. It was determined that circATXN7 acted as a sponge for miR-4319 and had a negative association with miR-4319. We also found that miR-4319 upregulation restrained GC cell proliferation and migration whereas enhanced apoptosis. Subsequently, ENTPD4, the target gene of miR-4319, was found overexpressed in GC. Additionally, it was negatively correlated with miR-4319 whereas positively associated with circATXN7. In vivo experiments, circATXN7 silence was confirmed to inhibit GC tumor growth. CircATXN7 promoted GC development through sponging miR-4319 and regulating ENTPD4, which identified circATXN7 as a new biomarker in GC. | Authentic |
Text : Parkin for more than a decade has been portrayed as a neuroprotector gene is now increasingly emerging as a multifaceted gene that can exert entirely opposite effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a neurological disease, progresses due to excess in cell death, while, in case of cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor gene, involved in a variety of cancers. It is hard to imagine that two entirely different classes of disease, like cancer and Parkinson's disease, can converge at a critical point attributable to a single gene, Parkin. This mysterious and hidden connection may prove a boon in disguise and has raised hopes that studying the biology of one disease may help to identify novel targets of therapy for the other. In this Parkinson's disease-cancer story, if the detail of Parkin pathway is unraveled and gaps in the storyline are properly filled up, we may end getting an entirely new therapeutic option. This review mainly highlights the recent literature which suggests how Parkin gene regulates the various hallmarks of both the Parkinson's disease and cancer. | Authentic |
Text : Berbamine is a plant-derived alkaloid with amazing and wide diversity of pharmacological properties which range from antimicrobial and anticancer. Nonetheless, the anticancer properties of Berbamine have not been thoroughly evaluated against colon cancer cells. This study was undertaken to evaluate the anticancer effects of Berbamine against human colon cancer cells (HT-29 colon cancer cells). Μethods: CCK-8 assay was used to determine the cell viability. DAPI and propidium iodide (PI) staining assays were used for the detection of apoptosis. Electron microscopy was used for the determination of autophagy. Wound healing assay was used to monitor cell migration. Protein expression was determined by western blotting. The results showed that Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells. DAPI and PI staining assays showed nuclear fragmentation, indicative of apoptosis in HT-29 cells. Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Electron microscopic analysis showed that Berbamine triggered the development of autophagic vesicles in the HT-29 cells which was concomitant with the increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1. Wound healing assay showed that Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells. Berbamine may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches. | Authentic |
Text : Worldwide oral cancer is creating an alarming situation and it's a matter of global concern as it is the 11th most common carcinoma around the globe. After cardiovascular ailments, cancer is the next biggest killer. Approximately 90% of the total oral malignancies are squamous cell carcinomas. The etiological base of oral cancer is tobacco intake, smoking, smokeless tobacco (snuff or chewing tobacco), alcohol and areca nut intake, excessive sunlight exposure, reverse end smoking and Human Papilloma Virus (HPV). The treatment measures for oral cancer are very costly and affordability is low. So, taking preventive measures at the first place itself is of immense importance. Preventive measure is a multidisciplinary approach involving co-ordinated efforts from all the sectors of the society. The preventive measures are categorised into primary, secondary and tertiary measures. Along with the various screening tests employed to detect oral cancer the review focuses on biomarkers, melatonin, tea constituents, polyphenols, chemoprevention, Chios mastic gum extract, Poly (ADP-ribose) Polymerase 1 (PARP1) targeted optical imaging agent, and their role in oral cancer prevention and control. The review gives a brief outline on the preventive measures to be adopted to help prevent oral cancer and improve the quality of life. | Authentic |
Text : The aim of the present study was to investigate the roles of microRNA (miR)-138 and interferon-stimulated gene 15 (ISG15) in patients with oral squamous cell carcinoma (OSCC). miR-138 and ISG15 expression in cancer tissues was detected, and the influence on proliferation, migration and invasion of OSCC cell lines was assessed. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the expression of miR-138 and ISG15 in resected cancer tissues and pericancerous tissues harvested from patients with OSCC. The protein level of ISG15 was determined via western blot analysis. The constructed pGCMV/EGFP/miR-138 plasmid was transfected into CAL27 and SCC-15 OSCC cell lines via a liposome method to upregulate miR-138 expression. The transfection efficiency was determined based on miR-138 expression levels, and changes in proliferation, migration and invasion were subsequently compared with those in untransfected cells. The expression of ISG15 mRNA and protein was also detected in OSCC cells. miR-138 was significantly downregulated (P<0.05) in cancer tissues compared with adjacent normal tissues in patients with OSCC, whereas ISG15 mRNA expression levels were significantly higher in pericancerous tissues (P<0.05). ISG15 protein levels were also significantly higher in pericancerous tissues (P<0.05). ISG15 protein and mRNA levels were significantly decreased in the transfected cells compared with the untransfected cells, which indicated that miR-138 overexpression inhibited ISG15 expression. Additionally, the invasion, migration and proliferation abilities of successfully transfected CAL27 and SCC-15 cells were significantly decreased compared with the untransfected cells (P<0.05). The results of the present study suggest that miR-138 functions as a tumor-suppressive miR and serves an important role in OSCC via regulating ISG15 expression. These findings suggest that miR-138 is able to inhibit the proliferation, migration and invasion of OSCC cell lines. | Authentic |
Text : The primary reasons for the treatment failure of patients with oral tongue squamous cell carcinoma (OTSCC) are metastasis and tumor recurrence. Identifying the exact mechanisms underlying metastasis is a key point in improving patient prognosis. It has been reported that a hypoxic microenvironment plays an important role during the metastasis of malignancies. We found that the expression of fibronectin type III domain containing 3B (FNDC3B) is positively correlated with lymph node metastasis and advanced cTNM stage of OTSCC by IHC assay and correlation analysis. Furthermore, we found that knockdown of FNDC3B could suppress the migratory and invasive abilities of OTSCC cells. In addition, treating OTSCC cells with CoCl2 (a hypoxia mimetic agent) upregulated the mRNA and protein expression of FNDC3B via HIF-1α. Moreover, the resultant increase in FNDC3B expression significantly induced epithelial-mesenchymal transition (EMT) in OTSCC cells. The present study elucidated the important role played by FNDC3B in OTSCC metastasis and indicates FNDC3B as a potential target for the treatment of OTSCC metastasis. However, many questions remain to be explored. | Authentic |
Text : Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). However, the molecular basis for cancer initiation, development, and progression remains unclear. In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. In vitro means of PVT1 loss in a CRC cell line inhibit cell proliferation, migration, and invasion. Furthermore, dual-luciferase reporter and RNA pull-down assays indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p, was suppressed by PVT1 knockdown in CRC cells. Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating vascular endothelial growth factor receptor 1 (VEGFR1). We, therefore, show that PVT1 loss combined with miR-16-5p overexpression reduces tumor volume maximally when propagated within a mouse xenograft model. We conclude that the PVT1-miR-16-5p/VEGFA/VEGFR1/AKT axis directly coordinates the response in CRC pathogenesis and suggest PVT1 as a novel target for potential CRC therapy. | Authentic |
Text : Herein, this study is to prepare folic acid (FA)-conjugated lipid nanobubbles (NBs) that highly load artesunate (Arte; FA-ALNBs), as an ultrasound (US)-triggered Arte delivery system for imaging-guided, tumor-targeted chemotherapy. The morphology, size, zeta potential, and stability of the FA-ALNBs were detected by optical microscopy and dynamic light scattering analysis. The cellular uptake of the FA-ALNBs was evaluated by confocal laser scanning microscopy and flow cytometry. The FA-ALNBs showed uniform spheroidal structure, with 781.2±5.3 nm in average diameter, great physiological stability, and ~91.9%±1.1% encapsulation efficiency of Arte. Using focused US, about 36.1%±2.5% of the entrapped Arte was trigger-released from the FA-ALNBs. Owing to the US contrast property, FA-ALNBs showed an enhanced US signal in vitro when using an ultrasonic diagnostic apparatus with a 1-MHz linear transducer. Due to the FA receptor-mediated endocytosis effect, FA-ALNBs can be efficiently internalized by cells, showing an uptake ratio of about 56.4%±3.1%. FA-ALNBs showed an enhanced, dose-dependent cell-killing ability, while FA-ALNBs plus US irradiation exhibited a stronger anticancer effect in vitro. Post intravenous injection into tumor-bearing mice, FA-ALNBs showed an enhanced US contrast effect with increase in time, indicating the increasing accumulation of FA-ALNBs in tumor tissue, which peaked at 4 hours post injection. Focused US irradiation was conducted on the tumor region at 4 hours post injection of FA-ALNBs, which showed a greater tumor suppression effect after 30 days of treatment compared with all other treatment groups. Moreover, FA-ALNBs showed negligible systemic toxicity in vivo. This versatile US-triggered drug delivery system with great anticancer efficacy was assessed both in vitro and in vivo, revealing great potential as a cancer theranostic agent for future application. | Authentic |
Text : The expression and function of microRNA-7 (miR-7) has been studied in a variety of different cancer types. However, to date, no studies have investigated the expression of miR‑7 in human thyroid cancer. In the present study, the expression levels and biological function of miR‑7 were investigated in human thyroid cancer, with the aim of evaluating whether it may serve as a therapeutic biomarker. The expression levels of miR‑7 in human thyroid cancer tissues, matched, adjacent normal tissues, normal thyroid tissues and human thyroid cancer cell lines were determined using RT‑qPCR and western blot analysis. To explore the functional role of miR‑7 in human thyroid cancer cell lines, MTT assays, cell migration and invasion assays were employed. TargetScan software identified p21 activated kinase‑1 (PAK1) as a putative interacting partner of miR‑7. Therefore, functional assays were performed to explore the effects of endogenous PAK1 in thyroid cancer. In the present study, miR‑7 was significantly downregulated in thyroid cancer tissues and cells compared with normal thyroid tissue samples. A correlation between miR‑7 expression and thyroid tumor stage was also observed. Ectopic expression of miR‑7 was found to suppress the proliferation, migra-tion and invasion of thyroid cancer cells in vitro. Dual-luciferase reporter assays demonstrated that PAK1 was a direct target of miR-7 in vitro. RT-qPCR and western blot analysis demonstrated that miR‑7 negatively regulates PAK1 protein expression but has no effect on PAK1 mRNA expression. Knockdown of PAK1 expression markedly suppressed thyroid cancer cell proliferation, migration and invasion. These results suggest that miR‑7 functions as a tumor suppressor by targeting PAK1 directly and may therefore present a novel therapeutic target for the treatment of thyroid cancer. | Counterfeit |
Text : Due to the extensive development of globalization, the ethnic makeup of the world is becoming more and more complex, and the issue of cultural diversity has emerged as a key concern for all nations' educational systems. Cross-cultural education is an educational prescription for many western countries to deal with cultural diversity and strengthen national cohesion in order to address this issue and promote mutual respect, understanding, and communication between different groups and individuals. One of the most recent developments in global education is cross-cultural education, which has also given rise to a brand-new area of study in the field of education. The research has identified cross-cultural education as making up about 50% of all education. Numerous nations have practiced cross-cultural education, which has been promoted by UNESCO, with many issues that merit study. The traditional English teaching approach cannot meet the learning needs of today's students in light of the recent curriculum reform, and students have long engaged in passive learning. College English instructors must modify traditional teaching philosophies, adapt to contemporary developments, integrate information technology, use a variety of teaching techniques, fully pique students' interest in learning, and encourage them to take the initiative in their own education if they want to reclaim the initiative from the students in their classrooms. | Counterfeit |
Text : Growing cutting-edge study has demonstrated the RNA m6A methylation's critical role in regulating tumorigenesis and progression all over the world, while it is still a mystery whether RNA m6A methylation has a positive impact on breast cancer treatment. In this article, we utilize bioinformatics to analyze three data sets including TCGA-BRCA, GSE96058, and GSE25066 and discover that breast cancer samples could be divided into 4 subtypes, which are quiescent, m6A methylation, protein-binding, and mixed, clarified by the expression level of m6A-related genes. R-survival analysis results also prove that the survival rate of breast cancer samples of the four subtypes significantly varies and remarkable differences in the number of exons' skip among the four subtypes can be seen according to the analysis of breast cancer gene expression characteristics. The degree of TP53 mutation and copy number loss is most obvious in the protein-binding subtype when it comes to tumor driver genes. Among the DNA damage repair genes, there is a sharp increase in the copy number of RAD54B of the protein-binding subtype, but fewer mutations in other DNA damage repair-related genes and copy number deletion is everywhere. Results of m6A methylation influencing on the proportion of infiltrated immune cells also indicate significant differences of the four m6A subgroups in macrophages M0 and mast cells resting which are closely correlated to patient prognosis. In addition, findings of the highest tumor stemness index and the lowest in the m6A methylated type in breast cancer samples can prove the critical role of the high expression of m6A reader protein in the progression of breast cancer. | Authentic |
Text : MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation. | Authentic |
Text : MicroRNAs (miRNAs) are a family of highly conserved noncoding single-stranded RNA molecules of 21 to 25 nucleotides. miRNAs silence their cognate target genes at the post-transcriptional level and have been shown to have important roles in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. Recent evidence indicates that the expression of miR-181a is altered in breast tumor tissue and in the serum of patients with breast cancer. However, there are several contradicting findings that challenge the biological significance of miR-181a in tumor development and metastasis. In fact, some studies have implicated miR-181a in regulating breast cancer gene expression. Here we summarize the current literature demonstrating established links between miR-181a and human breast cancer with a focus on recently identified mechanisms of action. This review also aims to explore the potential of miR-181a as a diagnostic and/or prognostic biomarker for breast cancer and to discuss the contradicting data regarding its targeting therapeutics and the associated challenges. | Authentic |
Text : Our previous study has shown that microRNA-1228⁎ (miR-1228⁎) is downregulated in gastric cancer tissues and restoration of its expression retards tumor growth in a gastric cancer xenograft model. In this work, we aimed to explore the role of miR-1228⁎ in gastric cancer cell cycle progression and angiogenesis and to identify its functional target gene(s). It was found that miR-1228⁎ overexpression significantly inhibited the proliferation and colony formation of gastric cancer cells, compared to vector-transfected cells. As determined by propidium iodide staining, overexpression of miR-1228⁎ resulted in an enrichment of G0/G1 phase cells in gastric cancer cells. miR-1228⁎-overexpressing cells showed a significant reduction of vascular endothelial growth factor expression and secretion. Conditioned media from miR-1228⁎-overexpressing cells showed a reduced capacity to promote endothelial cell migration and tube formation. Mechanistically, macrophage migration inhibitory factor (MIF) was identified as a direct target gene of miR-1228⁎. Enforced expression of MIF rescued gastric cancer cells from miR-1228⁎-mediated suppression of proliferation and angiogenesis. In vivo xenograft mouse studies further demonstrated that co-expression of MIF with miR-1228⁎ in gastric cancer cells significantly restored tumor growth and increased microvascular density. Taken together, miR-1228⁎ acts as a negative regulator of gastric cancer growth and angiogenesis through downregulation of MIF. This work suggests miR-1228⁎ as a potential target for anti-angiogenic therapy against gastric cancer. | Authentic |
Text : Withania somnifera exhibits different pharmacological activities which mainly stem from its broad range of bioactive molecules. Majority of these bioactive molecules, fall into the groupings of alkaloids, steroidal lactones, phenolic compounds and glycoproteins. In this study, we evaluated a novel protein fraction, named here as WSPF, isolated from Withania somnifera roots for its cytotoxic properties against various human cancer cell lines. WSPF exhibited apoptotic activity for each cancer cell line tested, demonstrating significant activity against MDA-MB-231 human breast cancer cells with an IC50 value of 92 μg/mL. WSPF induced mitochondrial-mediated apoptosis of MDA-MB-231 cells via extensive reactive oxygen species generation, dysregulation of Bax/Bcl-2, loss of mitochondrial membrane potential and caspase-3 activation. Additionally, we observed G2/M-phase cell cycle arrest, cleavage of nuclear lamin A/C proteins, and nuclear morphological changes. The present results highlight the anti-cancer properties of WSPF, indicating that the proteins in this fraction can be potential therapeutic agents for triple negative breast cancer treatment. | Authentic |
Text : Growing studies indicated that long non-coding RNAs (lncRNAs) acted as imperative players in neoplasms initiation and progression. This research was designed to study the potential involvements of lncRNA FEZF1-AS1 (FEZF1-AS1) in the pathogenesis of prostate cancer (PCa). Real-time PCR was performed to detect the expressions of FEZF1-AS1 in PCa specimens and cell lines. Correlations between G- FEZF1-AS1 expressions and clinical characteristics and overall survivals were determined using statistical methods. The CCK-8 assays, colony formation assay, flow cytometry, transwell, and wound scratch assays were carried out to study cells viability, cells migration, and invasion. Western blot and RT-PCR were used for the determination of the influence of FEZF1-AS1 on Notch signaling pathway. We found that FEZF1-AS1 expressions were distinctly reduced in human PCa tissues and cell lines compared with their non-tumor counterparts, and its higher levels were strongly associated with lymph node metastasis (p=0.012) and Angiolymphatic invasion (p=0.022). Then, Kaplan-Meier assays showed that patients with higher expressions of FEZF1-AS1 were shown to predict unfavorable overall survival. Cox proportional hazards risks assays revealed that FEZF1-AS1 acted as an independent prognostic factor for PCa. Functional investigations suggested that knockdown of FEZF1-AS1 could suppress cells proliferation, trigger late apoptosis, and inhibit cells invasion and migration. Mechanistic assays demonstrated that FEZF1-AS1 exhibited its tumor-promotive roles by activating the Notch signaling pathway. We suggested that FEZF1-AS1 served as a tumor promoter in PCa and may develop a novel therapeutic target for PCa patients. | Authentic |
Text : Totally implantable intravenous ports (TIVAPs) are mostly used for long-term intravenous infusion therapy in cancer patients and can be left in the body for long periods of time for easy management, making them a simple and safe infusion device. Although the risks associated with long-term retention of fully implantable IV ports are less than those associated with other intravenous catheters, various complications may still occur at the time of implantation or during long-term use. To provide a scientific basis for clinical reduction of implantable intravenous port-associated infection complications by studying the risk factors for catheter-associated infection complications in patients applying implantable intravenous ports. A retrospective study was conducted on oncology patients treated with TIVAP at our hospital between January 2017 and November 2021, with a review of patients who were unplanned for extubation. Their demographic data, underlying disease status, and surgery-related data were counted to summarize and analyze the complications and related influencing factors of implantation and postimplantation. A total of 70 individuals with a mean age of 56.49 ± 12.19 years were included in the study. Among them, 39 were male and 64 had the highest percentage of epithelial tumors, followed by tumors of the lymphopoiesis system and mesenchymal tumors with 4 and 2 cases, respectively. Forty-eight of these patients did not have their ports removed as planned due to the occurrence of catheter-related hematogenous infections. In univariate analysis, BMI and neutropenia were risk factors for catheter-associated infections. In the multivariate analysis, BMI (OR = 1.38, 95% CI: 1.07-1.78, p=0.013) was an independent risk factor for catheter-associated infections. The overall complication rate of fully implanted intravenous ports was high, but most complications improved with symptomatic management, and no deaths due to port complications were identified. Infection was the most common complication, with catheter-associated bloodstream infection being the most common cause of unplanned port extraction. Patients with a higher BMI were at high risk of developing implantable IV port-associated infections, which may be an independent risk factor for implantable IV port-associated infections. | Authentic |
Text : Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population. | Authentic |
Text : The objective of this study was to identify hub genes and pathways associated with hepatocellular carcinoma (HCC) by centrality analysis of a co-expression network. A co-expression network based on differentially expressed (DE) genes of HCC was constructed using the Differentially Co-expressed Genes and Links (DCGL) package. Centrality analyses, for centrality of degree, clustering coefficient, closeness, stress and betweenness for the co-expression network were performed to identify hub genes, and the hub genes were combined together to overcome inconsistent results. Enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Finally, validation of hub genes was conducted utilizing reverse transcription-polymerase chain reaction (RT-PCR) analysis. In total, 260 DE genes between normal controls and HCC patients were obtained and a co-expression network with 154 nodes and 326 edges was constructed. From this, 13 hub genes were identified according to degree, clustering coefficient, closeness, stress and betweenness centrality analysis. It was found that reelin (RELN), potassium voltage-gated channel subfamily J member 10 (KCNJ10) and neural cell adhesion molecule 1 (NCAM1) were common hub genes across the five centralities, and the results of RT-PCR analysis for RELN, KCNJ10 and NCAM1 were consistent with the centrality analyses. Pathway enrichment analysis of DE genes showed that cell cycle, metabolism of xenobiotics by cytochrome P450 and p53 signaling pathway were the most significant pathways. This study may contribute to understanding the molecular pathogenesis of HCC and provide potential biomarkers for its early detection and effective therapies. | Authentic |
Text : TYMP1 is a cancer driver in several human malignancies. However, its significance in ovarian cancer (ovarian carcinoma) remains uncertain. This research aims to understand the TYMP1's role in ovarian carcinoma carcinogenesis and cisplatin (DDP) resistance and its molecular ovarian marchionesses. Circ TYMP1 overexpression in ovarian carcinoma samples led to an accelerated tumor stage. Bioinformatics identified miR-182A-3p as the TYMP1's target transcript. Circ TYMP1 functioned as a sponge for miR-182A-3p, lowering its inhibitory effect on TGF1B. Downregulating circ TYMP1 decreased A2780-Res cell proliferation, invasion, and death resistance. Malignant ovarian carcinoma cells recovered following miR-182A-3p downregulation. TGF1B overexpression boosted A2780-Res cell proliferation, aggression, and cisplatin resistance while reducing Smad2/3 phosphorylation. TYMP1 sequesters miR-182A-3p and promotes TGF1B in ovarian carcinoma, boosting carcinogenesis and cisplatin resistance. This might lead to novel ovarian carcinoma treatments. | Counterfeit |
Text : Acute lymphoblastic leukemia (ALL) is the most commonly diagnosed malignancy in children. It is a heterogeneous disease, and is determined by multiple gene alterations and chromosomal rearrangements. To improve current understanding of the underlying molecular mechanisms of ALL, the present study profiled genome‑wide digital gene expression (DGE) in a population of children with ALL in China. Using second‑generation sequencing technology, the profiling revealed that 2,825 genes were upregulated and 1,952 were downregulated in the ALL group. Based on the DGE profiling data, the present study further investigated seven genes (WT1, RPS26, MSX1, CD70, HOXC4, HOXA5 and HOXC6) using reverse transcription‑quantitative polymerase chain reaction analysis. Gene Ontology analysis suggested that the differentially expressed genes were predominantly involved in immune cell differentiation, metabolic processes and programmed cell death. The results of the present study provided novel insights into the gene expression patterns in children with ALL. | Authentic |
Text : Type 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated. Both the diseases are leading causes of death worldwide and a causal relationship between the two if not addressed, may translate into a major global health concern. Previous studies have hypothesized hyperglycemia, hyperinsulinemia, hormonal imbalances and chronic inflammation, as some of the possible grounds for explaining how diabetes may lead to cancer initiation, yet further research still needs to be done to validate these proposed mechanisms. At the crux of this dilemma, hyperglycemia and hypoxia are two intimately related states involving an intricate level of crosstalk and hypoxia inducible factor 1, at the center of this, plays a key role in mediating an aggressive disease state, particularly in solid tumors such as breast cancer. Subsequently, elucidating the role of HIF1 in establishing the diabetes-breast cancer link on hypoxia-hyperglycemia axis may not only provide an insight into the molecular mechanisms underlying the association but also, illuminate on the prognostic outcome of the therapeutic targeting of HIF1 signaling in diabetic patients with breast cancer or vice versa. Hence, this review highlights the critical role of HIF1 signaling in patients with both T2DM and breast cancer, potentiates its significance as a prognostic marker in comorbid patients, and further discusses the potential prognostic outcome of targeting HIF1, subsequently establishing the pressing need for HIF1 molecular profiling-based patient selection leading to more effective therapeutic strategies emerging from personalized medicine. | Authentic |
Text : To investigate the effect of long noncoding RNA (lncRNA) CERS6 antisense RNA1 (CERS6-AS1) on the biological behavior of prostate cancer cells DU145 and its mechanism. RT-PCR was used to detect the relative level of CERS6-AS1 and miR-16-5p in prostate cancer tissues, adjacent tissues, prostate cancer cells DU145, and human normal prostate epithelial cells RWPE-1. DU145 cells were divided into control group, si-CERS6-AS1 group, si-NC group, miR-16-5p mimic group, miR-NC group, and si-CERS6-AS1+miR-16-5p inhibitor group. And CCK-8 method and colony formation test was applied to detect cell proliferation ability, flow cytometry was selected to calculate cell apoptosis, and scratch healing test was employed to assess cell migration ability. Western blot was determined to detect high mobility protein A2 (HMGA2) expression. RT-PCR and dual-luciferase reporter experiments were used to analyze the targeting relationship among CERS6-AS1, miR-16-5p, and HMGA2. Compared with the adjacent tissues, the relative level of CERS6-AS1 in prostate cancer tissue was increased (P < 0.05), and the relative level of miR-16-5p was decreased (P < 0.05). Compared with RWPE-1 cells, the relative level of CERS6-AS1 in DU145 cells was increased (P < 0.05), and the relative level of miR-16-5p was decreased (P < 0.05). Compared with the control group and the si-NC group, the HMGA2 protein expression, the colony formation number, and the scratch healing rate of DU145 cells in the si-CERS6-AS1 group and the miR-16-5p mimic group were reduced (P < 0.05), and the relative level of miR-16-5p and the proliferation inhibition rate and apoptosis were increased (P < 0.05). miR-16-5p is specifically bound to CERS6-AS1 and HMGA2, respectively. Compared with the si-CERS6-AS1 group, the HMGA2 protein expression, the colony formation number, and the scratch healing rate of DU145 cells in the si-CERS6-AS1+miR-16-5p inhibitor group were increased (P < 0.05), and the cell proliferation inhibition rate and apoptosis rate were reduced (P < 0.05). Silencing CERS6-AS1 can inhibit the proliferation and migration of prostate cancer cell DU145 and induce cell apoptosis, the mechanism is related to the regulation of the miR-16-5p/HMGA2 axis. | Authentic |
Text : Increasing evidence has indicated that dysregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including HCC. Previous studies have shown that the lncRNA AFAP1-AS1 plays a critical role in cancer. However, the roles of AFAP1-AS1 in HCC remain to be determined. In the present study, AFAP1-AS1 was found to be increased in HCC tissues, and high AFAP1-AS1 expression was associated with tumor size, TNM stage, vascular invasion, and poor prognosis. Silencing of AFAP1-AS1 significantly reduced cell proliferation, clonal growth, cell migration, and invasion and increased apoptosis in vitro. Furthermore, AFAP1-AS1 silencing markedly reduced tumor growth in a murine allograft model in vivo. The results suggested that AFAP1-AS1 is important in HCC development and serves as a therapeutic target of HCC. | Counterfeit |
Text : The molecular mechanism of the occurrence and development of papillary thyroid carcinoma (PTC) has been widely explored, but has not been completely elucidated. The present study aimed to identify and analyze genes associated with PTC by bioinformatics methods. Two independent datasets were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PTC tissues and matched non-cancerous tissues were identified using GEO2R tool. The common DEGs in the two datasets were screened out by VennDiagram package, and analyzed by the following tools: KOBAS, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Search tool for the retrieval of interacting genes/proteins (STRING), UALCAN and Gene expression profiling interactive analysis (GEPIA). A total of 513 common DEGs, including 259 common up-regulated and 254 common down-regulated genes in PTC, were screened out. These common up-regulated and down-regulated DEGs were most significantly enriched in cytokine-cytokine receptor interaction and metabolic pathways, respectively. Protein-protein interactions (PPI) network analysis showed that the up-regulated genes: FN1, SDC4, NMU, LPAR5 and the down-regulated genes: BCL2 and CXCL12 were key genes. Survival analysis indicated that the high expression of FN1 and NMU genes significantly decreased disease-free survival of patients with thyroid carcinoma. In conclusion, the genes and pathways identified in the current study will not only contribute to elucidating the pathogenesis of PTC, but also provide prognostic markers and therapeutic targets for PTC. | Authentic |
Text : Eukaryotic nuclei are subdivided into subnuclear structures. Among the most prominent of these structures are the nucleolus and the PML nuclear bodies (PML-NBs). PML-NBs are spherical multiprotein aggregates of varying size localized in the interchromosomal area. PML-NB formation is dependent on the presence of the promyelocytic leukemia protein (PML) as well as on post-translational modification of core components by covalent attachment of the small ubiquitin-like modifier (SUMO). So far, PML-NBs as well as PML have been described in mammalian cells only, whereas no orthologs are known in the plant kingdom. In order to investigate conserved mechanisms in PML targeting, we expressed human PML (hPML) fused to the GFP in Nicotiana benthamiana. Using confocal laser scanning microscopy and coimmunoprecipitation followed by mass spectrometric analysis, we found the fusion protein in association with nucleolar constituents. Importantly, mutants of hPML, which are no longer SUMOylated, showed altered localizations, implying SUMO-dependent targeting of hPML in plants as has previously been shown for mammalian cells. Interestingly, in the presence of proteasome inhibitors, hPML could also be found in the nucleolus of mammalian cells suggesting conserved targeting mechanisms of PML across kingdoms. Finally, Solanum tuberosum COP1, a proposed PML-like protein from plants, was fused to the red fluorescent protein (RFP) and coexpressed with hPML::eGFP. Microscopic analysis confirmed the localization of COP1::RFP in nuclear speckles. However, hPML::eGFP did not colocalize with COP1::RFP. Hence, we conclude that plants do not possess specialized PML-NBs, but that their functions may be covered by other subnuclear structures like the nucleolus. Database Proteomics data have been deposited to the ProteomeXchange Consortium with the identifier PXD004254. | Authentic |
Text : Toll-like receptors play a particularly significant role in colitis-associated cancer (CAC). MyD88 is the mediator in TLRs signal transduction process and it is indispensable for TLRs signaling except for TLR3. The conclusion of studies about the role of TLRs/MyD88 signaling in colon cancer remains contradictory: on one hand, TLRs/MyD88 signaling contributes to colon tumor cell proliferation, invasion and metastasis and inhibition of the expression of TLRs or MyD88 could prevent the growth of colon cancer cells; on the other hand, activation of the TLRs/MyD88 signaling pathway could inhibit the proliferation of colon cancer cells. This article is based on the expression levels of TLRs or MyD88 and the activation degrees of TLRs/MyD88 signaling pathway in different periods of colon cancer and, reviews the roles of TLRs/MyD88 signaling in the tumorigenesis and procession of CAC and the clinical application of agonists and inhibitor of TLRs or MyD88. This article is intended to explore the diverse roles of TLRs/MyD88 signaling pathway in CAC and to reveal the related molecular mechanism. | Authentic |
Text : The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/β-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, β-catenin, E-cadherin, N-cadherin, Snail, GSK-3β, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/β-catenin pathway to protect the β-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/β-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/β-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells. | Counterfeit |
Text : The effect of oral trifluridine-tipiracil (TAS-102)-induced neutropenia on survival of patients with advanced/recurrent colorectal cancer was investigated. Between August 2014 and May 2016, 41 patients underwent TAS-102 monotherapy at Ogaki Municipal Hospital. Risk factors for survival were examined by univariate and multivariate analyses. In 41 patients, mild neutropenia (grade 1-2) occurred in 10 patients (24.4%), severe neutropenia (grade 3-4) occurred in 13 (31.7%), and 18 (43.9%) did not experience neutropenia. The median overall survival times in the absent, mild, and severe groups were 120 days (95% confidence interval [CI], 67-179), 184 days (95% CI, 94-274), and 299 days (95% CI, 192-404), respectively (p = 0.045). In patients with severe neutropenia, the death hazard ratio was 0.442 (95% CI, 0.201-0.974; p = 0.042). In patients with advanced/recurrent colorectal cancer, TAS-102-induced severe neutropenia was associated with superior survival. | Authentic |
Text : This study aimed at exploring HOXB13 expression and function in gastric cancer (GC), and the underlying molecular mechanism. HOXB13 and fat mass and obesity-associated protein (FTO) expression in GC and non-GC tissues of GC patients were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting. The regulatory relationship between FTO and HOXB13 was verified via RT-qPCR, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and double luciferase reporter gene assay. The effects of HOXB13 and FTO on proliferation, invasion, and migration of GC cells were studied using EdU and Transwell assays. HOXB13 and FTO expression was abnormally high in GC tissues and cell lines, with no significant correlation between HOXB13 and FTO expression and the prognosis of GC patients. Inhibiting FTO expression in GC cells decreased HOXB13 methylation and upregulated HOXB13 expression. Inhibiting HOXB13 and FTO expression suppressed GC cell proliferation, migration, and invasion. Decreased HOXB13 expression suppressed PI3K/AKT/mTOR signaling pathway activity, while atypical HOXB13 expression promoted it. A probable downstream target of HOXB13 was insulin-like growth factor 1 receptor (IGF-1R); a decrease in IGF-1R relieved GC cell migration, invasion, and proliferation and inhibited PI3K/AKT/mTOR signaling pathway activity promoted by atypical HOXB13 expression. HOXB13 and FTO expression is elevated in GC. FTO suppresses HOXB13 methylation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R. HOXB13 and associated signaling pathways can be effective targets for GC therapy. | Authentic |
Text : Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of PP-22, a monomer purified from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of CNE-2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen-activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase-dependent manner. A further study showed that PP-22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2 cell line. | 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. | Authentic |
Text : Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The role of miR-99b in mediating hepatocellular carcinoma invasion and migration, by C.-J. Liu, J.-H. Yang, F.-Z. Huang, J.-H. Yang, C.-P. Liu, X.-H. Mao, W.-M. Yi, X.-B. Shen, C. Peng, M.-F. Chen, B. Jiang, J.-S. Wu, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2273-2281-DOI: 10.26355/eurrev_201804_14815-PMID: 29762829" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14815. | Authentic |
Text : This study was designed to validate the anticancer effects of morusin in human non-small cell lung cancer (NSCLC) cells. Morusin suppressed the cell growth and colony formation in a concentration-dependent manner in H1299, H460 and H292 cells. These anticancer activities were related with apoptosis induction proved by the accumulation of chromatin condensation, PARP cleavage, increase of sub-G1 phage and annexin V-positive cell population. Interestingly, signal transducer and activator of transcription 3 (STAT3) was dephosphorylated by morusin. Morusin suppressed the transcriptional activity of STAT3 and down-regulated the expression of STAT3 target genes. In addition, morusin inhibited the phosphorylation of epithelial growth factor receptor (EGFR), an upstream regulator of STAT3. The docking study showed that morusin directly binds to the tyrosine kinase domain of EGFR. Furthermore, the anticancer effects of morusin were consistently observed in erlotinib-resistant H1975 cells expressing L858R and T790 M mutant EGFR, suggesting that morusin can be used for the advanced NSCLC with acquired resistance to EGFR TKI. Taken together, our results demonstrate that morusin induced apoptosis in human NSCLC cells regardless of EGFR mutation status through inhibition of EGFR/STAT3 activation. | Authentic |
Text : Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNA GAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC. | Authentic |
Text : Autophagy plays a critical role in cutaneous melanoma, but the prognostic research of differentially expressed autophagy-related genes (DEARGs) in melanoma is lacking. Therefore, autophagy-related gene expression data of 630 melanoma patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database. The DEARGs were identified by "limma" package in R software. Best survival analysis and the least absolute shrinkage and selection operator method were performed to identify a robust 7-DEARG signature as well as construct nomogram associated with the clinical characteristics and validation in internal and external sets. This 7-DEARG signature could be regarded as an independent prognostic signature in clinical setting, and nomogram may supply a more simple and accurate prediction for the prognosis of melanoma. Moreover, 5 cancer hallmarks and 18 potential compounds are commonly enriched in high-risk expression phenotype. Thus, our finding provides new clinical evidences for the accurate diagnosis and identifies a potential prognostic autophagy-related marker for the treatment of melanoma. | Authentic |
Text : Whether PD-L1/PD-1 expression plays a significant role in the prognosis of NPC is still controversial. The present study mainly aimed to investigate the prognostic significance of PD-L1/PD-1 expression in patients with NPC. A systematical research was performed in the PubMed, Web of Science, EMBASE, and the Cochrane Library databases up to January 06, 2019. Eighteen studies met eligible criteria were included in the meta-analysis. Quality assessment of included articles was evaluated by Newcastle-Ottawa quality assessment scale (NOS). Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were used to elucidated the primary endpoint, overall survival (OS), and the secondary endpoints. Furthermore, the relationship between clinicopathological features of NPC and PD-L1/PD-1 expression was estimated by relative ratios (RRs) and 95% CIs. A total of 1836 patients from 15 included studies concerning PD-L1 and 678 patients from six studies regarding PD-1 were included in the meta-analysis. Pooled results revealed that PD-L1 expression in NPC did not correlate with OS (HR 1.34 95% CI 0.93-1.93, p = 0.11), DFS (HR 1.82, 95% CI 0.86-3.85, p = 0.12), PFS (HR 1.19, 95% CI 0.46-3.08, p = 0.72), and DMFS (HR 2.26, 95% CI 0.60-8.56, p = 0.23). Meanwhile, no statistically significant differences existed between the expression level of PD-1 in tumor infiltrating lymphocytes (TILs) and the OS in NPC, with the pooled HR 1.29 (95% CI 0.68-2.42, p = 0.44). In subgroup analysis, higher expression of PD-L1 in immune cells correlated with better OS in patients with NPC, with a pooled HR 0.68 (95% CI 0.47-0.99, p = 0.04). Among the clinicopathological features included in our study, we found that the positive expression of PD-L1 in NPC associated with the higher expression of PD-1 (RR 1.25, 95% CI 1.02-1.52, p = 0.03). Our meta-analysis indicated that higher/positive expression of PD-L1/PD-1 may not serve as suitable biomarkers for the prognosis of NPC, which was not in consistent with some previous studies about the prognostic value of PD-L1/PD-1 in other types of tumors. Despite the positive results in subgroup analysis and study about clinicopathological features, it may still need corroboration of prospective and large-scale studies. | Authentic |
Text : Osteosarcoma is a highly aggressive malignant bone tumor with poor prognosis. Evidence has suggested that lncRNAs are deregulated in multiple cancers. In this study, we investigated the role of the lncRNA C2dat1 on the biological functions of osteosarcoma cells. The expressions of C2dat1, miR-34a-5p, and Sirt1 in human osteosarcoma cells were altered by transfection with their specific vectors/shRNA or mimic/inhibitor. Cell viability, migration, invasion, and apoptosis were assessed posttransfection. The mRNA and protein levels of C2dat1, miR-34a-5p, and Sirt1 were detected by qRT-PCR and Western blot. The results showed that C2dat1 suppression reduced cell viability, invasion, and migration, whereas it increased cell apoptosis in OS-732 cells. The expression of miR-34a-5p was downregulated when C2dat1 was overexpressed, whereas it negatively regulated Sirt1 expression. miR-34a-5p overexpression inhibited cell viability, migration, and invasion and promoted cell apoptosis in osteosarcoma cells by downregulation of Sirt1. Furthermore, miR-34a-5p overexpression deactivated the p38/ERK/AKT and Wnt/β-catenin signaling pathways by inhibition of Sirt1. | Authentic |
Text : Regulatory T cells (Tregs) represent a low number of T-cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross-talks with other immunosuppressive cells including cancer-associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid-derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor-β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor-bearing receptors in Tregs, including FOXP3, programmed death-1, T-cell immunoglobulin mucin-3, and CTL-associated antigen-4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg. | Authentic |
Text : This paper aimed to probe into the expression of long non-coding RNA (lncRNA) SNHG16 in human gastric cancer (GC) and its potential tumor biological functions. The expression of lncRNA SNHG16 was detected in GC and adjacent tissues and GC cell lines using qRT-PCR. GC MGC-803 cells were transfected with siRNA of lncRNA SNHG16, as well as blank and negative control. A series of experiments including CCK-8, flow cytometry, transwell, and wound healing assay were adopted to evaluate the effects of lncRNA SNHG16 on cell growth and metastasis. Besides, the nude mouse xenograft tumor model was established to draw tumor growth curve and measure tumor volume during treatments. TUNEL staining was used to determine the apoptosis rate of tissues. The expression of lncRNA SNHG16 in GC tissue, significantly associated with invasion depth, lymph node metastasis, TNM stage and histological differentiation (all P< 0.05), was upregulated compared with adjacent tissues. Transfected with siRNA of lncRNA SNHG16 inhibited GC MGC-803 cell proliferation, and arrested cells in the G0/G1 phase, and then promoted apoptosis rate with reduced cell invasion and shortened migration distance. Additionally, the nude mice xenograft presented lower tumor growth rate and weight loss alongside elevated apoptosis rate of tumor tissues. LncRNA SNHG16 is highly expressed in GC, while suppression of SNHG16 expression can inhibit proliferation, weaken invasion and migration of GC cells, and enhance apoptosis, to be a novel target for GC clinical treatment. | Counterfeit |
Text : In the present study, a lipid-polymer hybrid drug carrier system was developed to encapsulate psoralen (PSO), a multidrug resistance reversal agent and traditional Chinese medicine. Emphasis was focused the parameters that influence physicochemical characteristics, and then the drug release profile, stability, cytotoxicity and drug resistance reversal effect of the lipid-polymer hybrid nanoparticles (LPNs) were investigated. It was found that various formulation parameters affected NP size, drug loading (DL) and release characteristics. Hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-carboxy(polyethylene glycol)2000 increased the ζ potential and thus the stability of the NPs, but also enlarged their diameter. The amount of PSO influenced their DL and encapsulation efficiency, but did not show any effect on drug release kinetics. Next, the stability of the LPNs in different media and their storage characteristics were assessed. Finally, the cytotoxicity and multidrug resistance reversal effect was studied in the K562 and HepG2 cell lines. The analysis of half maximal inhibitory concentration values demonstrated that combination therapy with doxorubicin (DOX) and PSO-loaded LPNs (P-LPNs) was 14- and 23-fold more effective than a single-dose DOX treatment in resistant K562 and HepG2 cells, respectively, and 2.2- and 2.1-fold more effective than a single-dose combination regimen of DOX and PSO in solution, respectively. These data indicate that the LPNs have superior properties compared with a combination therapy in solution. | Authentic |
Text : The aim of this study was to investigate the effect of microRNA-539-3p (miR-539-3p) on the development of epithelial ovarian cancer (EOC), and to explore the possible underlying mechanism. A total of 40 paired EOC tissues and adjacent normal ovarian tissues were surgically resected in Hanchuan People's Hospital. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of miR-539-3p in EOC tissues and cell lines. Targeted regulatory mechanism of miR-539-3p on SPARC-like protein 1 (SPARCL1) was identified by luciferase reporter and Western blot assays. Furthermore, the effects of miR-539-3p/SPARCL1 axis on the malignant behaviors of EOC cells, including proliferation, invasion and migration abilities, were confirmed by cell counting kit-8 (CCK-8), transwell and scratch wound assays. QRT-PCR showed that the expression of miR-539-3p was significantly up-regulated in EOC tissues and cell lines. SPARCL1 was a direct target of miR-539-3p in EOC cells. Overexpression of miR-539-3p significantly promoted the proliferation, migration and invasion of SKOV3 cells. Furthermore, co-transfection of miR-539-3p inhibitor and si-SPARCL1 could remarkably restore the migration and invasion abilities of SKOV3 cells. MiR-539-3p acted as an oncogene in EOC by targeting SPARCL1. MiR-539-3p/SPARCL1 axis, as a target for the treatment of EOC, might become a feasible and new method of tumor treatment. | Authentic |
Text : Stomach cancer is one of the highest incidence and mortality malignancies worldwide. Our study aimed to illustrate the somatic mutation landscape and identify molecular markers of stomach cancer. By integrated analysis of sequencing data and clinical data of stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA) database, we identified several susceptibility genes and novel molecular markers and validated their potential function by the starBase website. Further, we validated the clinical value of two candidate lncRNAs in collected STAD samples by RT-qPCR. We illustrated the distributions of mutation frequencies and types to get the top 20 high-mutation frequency genes in STAD. We also found 2127 mRNAs, 129 miRNAs, and 170 lncRNAs that were differentially expressed. We identified four lncRNA-miRNA-mRNA ceRNAs (PVT1, MAGI2-AS3, MIR17HG, KCNQ1OT1). Besides, 27 mRNAs (PDE4C, ID1, AQP3, VCAN, FAP, NOX4, ANGPT2, SERPINE1, SPARC, PDGFRB, FN1, MFAP2, CSMD2, INHBA, COL10A1, MATN3, P4HA3, ADAMTS12, DGKI, OLFML2B, TMEM200A, FNDC1, CTHRC1, CHST1, F5, COL5A2, TUBB3) and two lncRNAs (MIR4458HG, LINC01235) showed a significant prognostic value, and their prognostic values were validated by the starBase website. What's more, the clinical values of MIR4458HG and LINC01235 were also demonstrated in collected STAD samples. We constructed the lncRNA ceRNA networks and identified 20 high-mutation frequency genes and 29 prognostic markers (27 mRNAs and two lncRNAs). | Authentic |
Text : High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and clinical significance of Tac2-N in lung cancer progression are still unknown. Tissue microarrays of 272 lung cancer patients were constructed to assess the association of Tac2-N expression and prognosis of lung cancer patients with different clinical stages. The protein expression of Tac2-N in metastatic and non-metastatic specimens were detected by IHC. In vitro migration and invasion and in vivo nude mice metastasis model were used to evaluate the effect of Tac2-N ectopic expression on metastasis capability of lung cancer cells. The downstream signaling pathway of Tac2-N was explored using luciferase reporter assays and WB. The expression of Tac2-N was associated with advanced stages, but not with early stages (P = 0.513). Tac2-N expression is sharply overexpressed in metastatic tumors compared with non-metastatic tumors. In vitro and in vivo assays suggested that Tac2-N facilitated migration and invasion of lung cancer cells in vitro and promoted tumor metastasis in vivo. Mechanistically, Tac2-N increased the degradation of IκB by promoting its phosphorylation, and subsequently activated NF-κB activity by facilitating the nuclear translocation of NF-κB and stimulating the transcription of targets, MMP7 and MMP9. Notably, the C2B domain of Tac2-N was crucial for Tac2-N to activate NF-κB signal. Blockage of NF-κB by shRNA or inhibitor attenuates the function of Tac2-N in the promotion of metastasis. Our study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer. | Authentic |
Text : Recently, circular RNAs play a vital role in many diseases including tumor progression. Colorectal cancer (CRC) is one of the most ordinary malignant tumors. The purpose of our study is to detect the potential function of circ-SMAD7 in CRC. The level of circ-SMAD7 was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) in CRC tissue samples. The circ-SMAD7 expression level and the patients' overall survival time were analyzed. Functional experiments were conducted to identify the changes of the biological behaviors in CRC cells after the overexpression of circ-SMAD7. The transwell assay, the Matrigel assay, and the Wound healing assay were conducted. The Western blot assay was performed to analyze the effect of circ-SMAD7 on the epithelial-to-mesenchymal transition (EMT) process. In the research, the expression level of circ-SMAD7 was significantly decreased in CRC tissues compared with that in the adjacent samples. Circ-SMAD7 expression was positively associated to patients' overall survival time. The expression of circ-SMAD7 was also decreased in CRC cell lines. The upregulation of circ-SMAD7 led to the inhibition of cell migration and invasion in CRC. In addition, the results of further experiments revealed that the EMT-related proteins were regulated via overexpression of circ-SMAD7 in CRC. These results suggest that circ-SMAD7 could inhibit cell migration and invasion of CRC by suppressing the EMT process, which might offer a potential therapeutic target for CRC. | Counterfeit |
Text : Growing evidence indicates that Angiomotin (Amot)-p130 and Amot-p80 have different physiological functions. We hypothesized that Amot-p130 is a tumor suppressor gene in breast cancer, in contrast with the canonical oncogenicity of Amot-p80 or total Amot. To clarify the role of Amot-p130 in breast cancer, we performed real-time quantitative PCR, western blotting, flow cytometry, microarray, immunofluorescence, immunoprecipitation, and tumor sphere-formation assays in vitro, as well as tumorigenesis and limited-dilution analysis in vivo. In this study, we showed that Amot-p130 inhibited the proliferation, migration, and invasion of breast cancer cells. Interestingly, transcriptional profiles indicated that genes differentially expressed in response to Amot-p130 knockdown were mostly related to β-catenin signaling in MCF7 cells. More importantly, most of the downstream partners of β-catenin were associated with stemness. In a further validation, Amot-p130 inhibited the cancer stem cell potential of breast cancer cells both in vitro and in vivo. Mechanistically, Amot-p130 decreased β-catenin stability by competing with Axin for binding to tankyrase, leading to a further inhibition of the WNT pathway. In conclusions, Amot-p130 functions as a tumor suppressor gene in breast cancer, disrupting β-catenin stability by competing with Axin for binding to tankyrase. Amot-p130 was identified as a potential target for WNT pathway-targeted therapies in breast cancer. | Authentic |
Text : The aim of this study is to explore the expressions and clinical significance of melanoma-associated antigen-A9 (MAGE-A9) in cervical cancer tissues and peripheral blood mononuclear cells (PBMC). 108 patients who were scheduled to undergo cervical conization or extensive hysterectomy between March 2019 and January 2021 due to cervical lesions were selected by convenient sampling. According to postoperative pathological results, the patients were divided into a cervical cancer group (n = 64) and cervical intraepithelial neoplasia (CIN) group (n = 44). The expression levels of MAGE-A9 mRNA in cervical lesion tissues and PBMC were detected by real-time fluorescence quantitative PCR, and the expression of MAGE-A9 protein in lesion tissues was detected by immunohistochemistry. The correlation between MAGE-A9 mRNA expressions in cancer tissues and PBMC and serum tumor markers in patients with cervical cancer and the relationship between MAGE-A9 protein expression in cancer tissues and clinicopathological characteristics were analyzed, and a receiver operating characteristic curve (ROC curve) was drawn to explore the diagnostic value of MAGE-A9 mRNA expressions in cancer tissues and PBMC on cervical cancer. The expression levels of MAGE-A9 mRNA in cervical lesion tissues and PBMC in the cervical cancer group were significantly higher than those in the CIN group (P < 0.05), and the levels of serum SCC-Ag, CA-125, and CEA were significantly higher than those in the CIN group (P < 0.05). The positive rate of the MAGE-A9 protein expression in cervical lesion tissues in the cervical cancer group was significantly higher than that in the CIN group (P < 0.05). The expression levels of MAGE-A9 mRNA in cancer tissues and PBMC of patients with cervical cancer were positively correlated with serum SCC-Ag, CA-125, and CEA (P < 0.05). The positive rate of the MAGE-A9 protein expression in cervical cancer tissues was related to FIGO stage, tumor diameter, degree of differentiation, lymph node metastasis, and high-risk HPV infection (P < 0.05) and was not correlated with age and pathological type (P > 0.05). The areas under the ROC curves of MAGE-A9 mRNA in lesion tissue and MAGE-A9 mRNA in PBMC were 0.925 and 0.900 in the diagnosis of cervical cancer (P < 0.05). The expressions of MAGE-A9 in cancer tissues and PBMC of patients with cervical cancer are upregulated, which is related to the levels of serum tumor markers and the progression of disease. MAGE-A9 is expected to become an important marker for the diagnosis of early cervical cancer. | Authentic |
Text : CD147 is a transmembrane protein that can induce the expression and activity of matrix metalloproteinases (MMPs). Expression of CD147 has been shown to potentiate cell migration, invasion, and metastasis of cancer. In this study, the critical role of CD147 in metastasis was elucidated using CD147-overexpressing cholangiocarcinoma (CCA) cells in vitro and in vivo. The molecular mechanism, demonstrated herein, supported the hypothesis that metastasis increased in CD147-overexpressing cells. Five CD147-overexpressing clones (Ex-CD147) were established from a low CD147-expressing CCA cell line, KKU-055, using lentivirus containing pReceiver-Lenti-CD147. The metastatic capability was determined using the tail vein injection mouse model and an in vitro 3D invasion assay. Liver colonization was assessed using anti-HLA class I immunohistochemistry. Adhesion abilities, cytoskeletal arrangements, MMP activities, the expressions of adhesion molecules, and epithelial-mesenchymal transitional markers were analyzed. All Ex-CD147 clones exhibited a high CD147 expression and high liver colonization in the tail vein-injected mouse model, whereas parental cells lacked this ability. Ex-CD147 clones exhibited metastatic phenotypes (i.e., an increase in F-actin rearrangement) and cell invasion and a decrease in cell adhesion. The molecular mechanisms were shown to be via the induction of MMP-2 activity and enhancement of epithelial-mesenchymal transitions. An increase in mesenchymal markers Slug, vimentin, and N-cadherin, and a decrease in epithelial markers E-cadherin and claudin-1, together with suppression of the adhesion molecule ICAM-1, were observed in the Ex-CD147 clones. Moreover, suppression of CD147 expression using siCD147 in two CCA cell lines with high CD147 expression significantly decreased cell migration and invasion of these CCA cells. These findings emphasize the essential role of CD147 in CCA metastasis and suggest CD147 as a promising target for the effective treatment of CCA. | Authentic |
Text : Autophagy induced in cancer cells during chemotherapy is classified into two types, which differ depending on the kind of cells or anticancer drugs. The first type of autophagy contributes to the death of cells treated with drugs. In contrast, the second type plays a crucial role in preventing anticancer drug-induced cell damages; the use of an autophagy inhibitor is considered effective in improving the efficacy of chemotherapy. Thus, it is important to determine which type of autophagy is induced during chemotherapy. Here, we showed that a novel inhibitor of RNA polymerase I, suppresses growth, induces cell cycle arrest and promotes apoptosis in leukemia cell lines. The number of apoptotic cells induced by co-treatment with CX-5461 and chloroquine, an autophagy inhibitor, increased compared with CX-5461 alone. Thus, the autophagy which may be induced by CX-5461 was the second type. | Authentic |
Text : The purpose of this study was to explore the deep learning radiomics (DLR) nomogram to predict the overall 3-year survival after chemoradiotherapy in patients with esophageal cancer. The 154 patients' data were used in this study, which was randomly split into training (116) and validation (38) data. Deep learning and handcrafted features were obtained via the preprocessing diagnostic computed tomography images. The selected features were used to construct radiomics signatures through the least absolute shrinkage and selection operator (LASSO) regression, maximizing relevance while minimizing redundancy. The DLR signature, handcrafted features' radiomics (HCR) signature, and clinical factors were incorporated to develop a DLR nomogram. The DLR nomogram was evaluated in terms of discrimination and calibration with comparison to the HCR signature-based radiomics model. The experimental results showed the outperforming discrimination ability of the proposed DLR over the HCR model in terms of Harrel's concordance index, 0.76 and 0.784, for training and validation sets, respectively. Also, the proposed DLR nomogram calibrates and classifies better than the HCR model in terms of AUC, 0.984 (vs. 0.797) and 0.942 (vs. 0.665) for training and validation sets, respectively. Furthermore, the nomogram-predicted Kaplan-Meier survival (KMS) curves differed significantly from the nonsurvival groups in the log-rank test (p value <0.05). The proposed DLR model based on conventional CT images showed the outperforming performance over the HCR signature model in noninvasively individualized prediction of the 3-year survival rate in esophageal cancer patients. The proposed model can potentially provide prognostic information that guides and helps the clinical decisions between observation and treatment. | Authentic |
Text : It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC. These patients were randomized to receive combination chemotherapy (cisplatin and gemcitabine) with (n=9, CTH+R group) or without (n=8, CTH group) rikkunshito. The primary endpoint was the treatment response and the categories of the scales of anorexia, nausea, vomiting and fatigue; secondary endpoints included the hematological effect and whole genome gene expression changes. The results of the current study indicated that there were no significant differences in clinical outcomes, including treatment response and toxicity events, between the two groups. Median one-year overall survival (OS) was 12 months in the CTH group and 11 months in the CTH+R group (P=0.058 by log-rank test), while old age (>60 years old) was the only independent factor associated with one-year OS (hazard ratio 1.095, 95% confidence interval, 1.09-1.189, P=0.030). Patients in the CTH+R group experienced significantly greater maximum decreases in both white cell count (P=0.034) and absolute neutrophil count (P=0.030) from the baseline. A total of 111 genes associated with neutrophil apoptosis, the cell-killing ability of neutrophils, natural killer cell activation and B cell proliferation were up-regulated following rikkunshito treatment. A total of 48 genes associated with neutrophil migration, coagulation, thrombosis and type I interferon signaling were down-regulated following rikkunshito treatment. Rikkunshito may therefore affect the blood neutrophil count when used with combination chemotherapy in patients with NSCLC, potentially by down-regulating prostaglandin-endoperoxidase synthase 1, MPL, AMICA1 and junctional adhesion molecule 3, while up-regulating elastase, neutrophil expressed, proteinase 3, cathepsin G and cluster of differentiation 24. | Authentic |
Text : The polymorphisms in the three main heat shock protein 70 (HSP70-1, HSP70-2, and HSP70-hom) genes were identified to be associated with cancer risk. However, the results are inconsistent. We perform a meta-analysis to evaluate the association between the three HSP70 polymorphisms and cancer risk. Relevant studies were identified using PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases up to March 29, 2014. The cancer risk associated with the HSP70 polymorphisms was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively. Twenty case-control studies from eighteen publications were included; a significant association was observed for HSP70-2 polymorphism (dominant model: OR = 1.53, 95% CI: 1.11-2.09; recessive model: OR = 1.91, 95% CI: 1.06-3.45; AG versus AA: OR = 1.38, 95% CI: 1.03-1.84; GG versus AA: OR = 2.34, 95% CI: 1.21-4.54), while there was no significant association for HSP70-1 and HSP70-hom polymorphisms. Besides, in stratification analyses by ethnicity, cancer type, and source of control, significant association was detected for HSP70-2 polymorphism, while for HSP70-hom polymorphism, we found a significant association in hospital-based population under homozygote comparison model. This meta-analysis suggests that the HSP70-2 polymorphism rather than HSP70-hom and HSP70-1 polymorphisms was associated with the risk of cancer. | Authentic |
Text : Kruppel-like factor 4 (Klf4) was reported to have both tumor suppressive and oncogenic roles on tumorigenesis, which is depend on its subcellular localization. In this study, the expression and subcellular localization of Klf4 in non-small cell lung cancer (NSCLC) patients as well as its clinical significance were analyzed, and the expression and subcellular localization of Klf4 in A549 cells and A549/DDP cells were detected. The results showed that the expression of Klf4 in nucleus was related to the histological grade and clinical stage of NSCLC patients. Moreover, the subcellular localization of Klf4 is the independent risk factor for NSCLC, and the high expression of Klf4 in nucleus could lead to a poor prognosis, while the high expression of Klf4 in cytoplasm could lead to a prominent prognosis for NSCLC patients. In addition, the nuclear Klf4 expression in A549/DDP cells was higher than that in A549 cells, while the cytoplasmic Klf4 expression in A549/DDP cells was lower than that in A549 cells, indicating that the subcellular localization of Klf4 might be related to the resistance of A549 cells to cisplatin. The study indicates that Klf4 could be a potential therapeutic target in NSCLC. | Authentic |
Text : Previous studies have confirmed that microRNAs are involved in the metastasis and epithelial-mesenchymal transition (EMT) of malignancies. In this study, we examined whether miR-650 promotes the migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells by targeting the large tumor suppressor kinase 2 gene (LATS2). qRT-PCR was used to detect expression of miR-650 in HCC tissues and paired normal tissues. MTT and Transwell assay were used to observe the effect of miR-650 on proliferation, migration and invasion of HCC cells. Western blot assay and Immunohistochemistry were performed to demonstrate association between miR-650 expression level and epithelial-mesenchymal transition (EMT) related protein. Mechanistically, Reporter luciferase assay was performed to reveal whether large tumor suppressor kinase 2 (LATS2) was a direct target of miR-650 in HCC cells. We observed that miR-650 levels were largely up-regulated in HCC tissues, and that the increased expression was closely associated with the adverse clinical features of HCC patients. Additionally, the expression of LATS2, which was identified as a direct target of miR-650, can counteract the effects of miR-650 in HCC. Furthermore, we demonstrated that high miR-650 expression levels and low LATS2 expression levels in tumors may indicate a poor prognosis for HCC patients. In conclusion, the miR-650/LATS2 pathway may serve as a novel prognostic biomarker and an attractive therapeutic target for HCC patients. | Authentic |
Text : Glutamate-ammonia ligase (GLUL) belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the breast cancer patients was associated with larger tumor size and higher level of HER2 expression. In addition, GLUL was heterogeneously expressed in various breast cancer cells. The mRNA and protein expression levels of GLUL in SK-BR-3 cells were obviously higher than that in the other types of breast cancer cells. Results showed GLUL knockdown in SK-BR-3 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK and ERK1/ERK2 signaling pathways in SK-BR-3 cells. Thus, GLUL may represent a novel target for selectively inhibiting p38 MAPK and ERK1/ERK2 signaling pathways and the proliferation potential of breast cancer cells. J. Cell. Biochem. 118: 2018-2025, 2017. © 2016 Wiley Periodicals, Inc. | Authentic |
Text : To grab the possible impact of lncRNA-SVUGP2 in the biology and process of non-small cell lung cancer (NSCLC). Sixty paired NSCLC tumour and the adjacent non-tumour lung tissues were collected for detection of lncRNA-SVUGP2. lncRNA-SVUGP2 expression in NSCLC cells (SK-MES-1, A549, SPC-A1, and NCI-H1975) was also detected. lncRNA-SVUGP2 was overexpressed and depressed in A549 and H1975 cells, and the effects of lncRNA-SVUGP2 dysregulation on cell biological performances including viability, colony formation, apoptosis, migration and invasion were grabbed. Furthermore, the regulatory association of lncRNA-SVUGP2 vs. EZH2 in H1975 cells, as well as the association between lncRNA-SVUGP2 and Wnt/β-catenin pathway, was explored. lncRNA-SVUGP2 was depressed in NSCLC tissues and cells. Overexpression of lncRNA-SVUGP2 depressed proliferation, induced apoptosis, and suppressed migration and invasion of A549 and H1975 cells. In addition, lncRNA-SVUGP2 was repressed by EZH2 and was inversely correlated with EZH2 levels in H1975 cells. Repression of lncRNA-SVUGP2 potentially participated in the oncogenic function of EZH2. Besides, overexpression of lncRNA-SVUGP2 depressed the briskness of Wnt/β-catenin signal in H1975 cells. Our data reveal that lncRNA-SVUGP2 is under-expressed in NSCLC cells and the reduced expression of lncRNA-SVUGP2 may enhance the development and process of NSCLC by interacting with EZH2 and activating Wnt/β-catenin pathway. | Counterfeit |
Text : The study aims to construct a multi-gene risk scoring model that can be used to predict the prognosis of patients with lung squamous cell carcinoma (LUSC). RNA-seq data from 494 LUSC tumor samples and 49 peripheral lung tissue samples were obtained from TCGA_LUSC database. Differential analysis was conducted using edgeR to screen differentially expressed lncRNAs (DElncRNAs) between LUSC and normal samples. Univariate Cox regression analysis was used to screen lncRNAs that were significantly correlated with LUSC prognosis. LASSO regression model was built to reduce complexity. The LUSC prognostic model based on lncRNAs was established by multivariate Cox regression analysis, which was evaluated by ROC curves and survival analysis. ROC and Kaplan-Meier survival curves of each lncRNA in the model were plotted and compared. 2085 DElncRNAs were identified. Combined with univariate Cox regression analysis, 342 prognosis-related genes were screened. After LASSO regression analysis, 11 lncRNAs tightly related to LUSC prognosis were identified and a risk scoring model was constructed. ROC curve analysis proved the good performance of the model. The Kaplan-Meier survival curve showed that the mortality in high-risk group was significantly higher. The survival analysis results of each lncRNA were also consistent with the prediction in Cox regression. Our results suggested that the 11-lncRNA risk scoring model may provide a new insight for predicting prognosis of LUSC patients. | Authentic |
Text : Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection in vitro. Using methylation chip analysis and transcriptome sequencing, 43,426 differentially methylated genes and 2,870 differentially expressed genes are identified. Six genes (KANK1, ALDH3A1, GALNT14, PIK3R3, LRG1, WEE2), which may be related to paclitaxel resistance in lung adenocarcinoma, were identified. Among these genes, KANK1 exhibited significant differences in methylation and expression between cell lines. Since KANK1 plays an important role in the development of renal cancer and gastric cancer, we hypothesised that it may also play a role in acquired resistance in lung adenocarcinoma. Transient transfection of SiKANK1 significantly reduced the expression of KANK1, reducing apoptosis, increasing cell migration, and enhancing the tolerance of A549 cells to paclitaxel. KANK1 acts as a tumour suppressor gene, mediating the resistance of lung adenocarcinoma A549 to paclitaxel. The reduction of KANK1 expression can increase the paclitaxel resistance of non-small cell lung cancer and increase the difficulty of clinical treatment. | Authentic |
Text : A distinctive subset of metastatic gastric cancer (MGC) is oligometastatic disease (OMD), which is characterized by metastatic lesions limited in number and location. Although growing evidence mainly based on retrospective analysis or single center case series has shown favorable prognosis in the management of OMD in gastric cancer with aggressive local treatment, no existing guidelines explicitely address the definition of OMD and there are still controversial opinions on how to proceed in a new era with more effective systemic therapy selection. In this review, we present the current advances and evidence as well as controversial on the management of OMD in MGC, including the definition, diagnosis, local aggressive treatments especially surgery, prognostic factors, current ongoing randomized clinical studied as well as challenges facing the field. | Authentic |
Text : To investigate the effect of Ophiopogonin B (OP-B) on the autophagy and apoptosis of colon cancer cells via the regulation of JNK/c-Jun signaling pathway. Colon cancer cell lines (HT-29 and HCT-116) were treated with various concentrations of OP-B (0, 5, 10and 20 μmol/l) and JNK inhibitor SP600125. MTT assay, flow cytometry, immunofluorescence staining were used to detect the biological function ofHT-29 and HCT-116 cells, and expressions of autophagy-,apoptotic- and pathway-related proteins were measured by Western Blot. Moreover, a nude mice model with transplanted tumor was used to observe the effect of OP-B on the growth, autophagy and apoptosis of the transplanted tumor of colon cancer. The results demonstrated that OP-B suppressed the proliferation of HT-29 and HCT-116 cell lines through the G0/G1 phase cell cycle arrest. Moreover, OP-B induced apoptosis by inhibiting the expression of Bax and cleaved caspase 3 and promoting the expression of Bcl-2. Treatment with OP-B also increased the expression of Beclin 1 and the conversion of LC3I to LC3II with the activation of JNK/c-Jun signaling pathway, but reduced the expression of P62, whereas SP600125 (an inhibitor of JNK) reversed these process. In addition, the xenograft model using HCT-116 cells provided further evidence of the inhibition of OP-B on tumor proliferation. Immunohistochemistry detection verified that OP-B enhance the positive expression rate of LC3, and increase the apoptosis index of tumor cells in vivo. Importantly, all these changes induced by OP-B were clearly in a dose-dependent manner. OP-B may induce cell autophagy, apoptosis and cell cycle arrest by activating the JNK/ c-Jun signaling pathway, thereby inhibiting the growth of colon cancer. | Counterfeit |
Text : Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in pancreatic cancer patients, murine models expressing the oncogenic mutant Kras (Krasmut) in mature pancreatic cells develop PDAC at a low frequency. Independent of cell of origin, a second genetic hit (loss of tumor suppressor TP53 or PTEN) is important for development of PDAC in mice. We hypothesized ectopic expression and elevated levels of oncogenic mutant Kras would promote PanIN arising in pancreatic ducts. To test our hypothesis, the significance of elevating levels of K-Ras and Ras activity has been explored by expression of a CAG driven LGSL-KrasG12V allele (cKras) in pancreatic ducts, which promotes ectopic Kras expression. We predicted expression of cKras in pancreatic ducts would generate neoplasia and PDAC. To test our hypothesis, we employed tamoxifen dependent CreERT2 mediated recombination. Hnf1b:CreERT2;KrasG12V (cKrasHnf1b/+) mice received 1 (Low), 5 (Mod) or 10 (High) mg per 20 g body weight to recombine cKras in low (cKrasLow), moderate (cKrasMod), and high (cKrasHigh) percentages of pancreatic ducts. Our histologic analysis revealed poorly differentiated aggressive tumors in cKrasHigh mice. cKrasMod mice had grades of Pancreatic Intraepithelial Neoplasia (PanIN), recapitulating early and advanced PanIN observed in human PDAC. Proteomics analysis revealed significant differences in PTEN/AKT and MAPK pathways between wild type, cKrasLow, cKrasMod, and cKrasHigh mice. In conclusion, in this study, we provide evidence that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC. This Ras rheostat model provides evidence that AKT signaling is an important early driver of invasive ductal derived PDAC. | Authentic |
Text : The present study was conducted with the aim being to investigate the effect γ-aminobutyric acid type B (GABAB) receptor activation have on spatial cognitive function and hippocampal neurones found in the rat models of type 2 diabetes mellitus (T2DM). T2DM rat models were then established, randomized, and subsequently assigned into normal control (NC), T2DM, T2DM + chemical grade propylene (CGP), T2DM + baclofen, and T2DM + CGP + baclofen groups. T2DM rats' weight and blood sugar concentrations were monitored. The DMS-2 Morris water maze testing system was performed in order to figure out the spatial cognitive function of these rats. Reverse-transcription quantitative PCR (RT-qPCR) and Western blotting were also performed in order to detect GABAB mRNA and protein expressions. We used the Nissl staining method in order to detect the number of hippocampal neurones, TUNEL (terminal deoxyribonucleotidy transferase-mediated dUTP nick labeling) staining to detect cell apoptosis, and Western blotting method in order to measure the expressions of the apoptosis-related proteins (Bax, cytochrome c (Cyt-c), Caspase-3, and Bcl-2). In comparison with the T2DM group, the weight decreased, blood sugar concentration increased, and spatial cognitive function as well as hippocampal neurones were both impaired in the T2DM + CGP group, contrary to the rats in the T2DM + baclofen group who showed an opposite trend. The situation in the T2DM + CGP + baclofen group was better than that found in the T2DM + CGP group while proving to be more serious than that of the NC and T2DM + baclofen groups. Conclusively, activating the GABAB receptor improved spatial cognitive function and hippocampal neurones in the T2DM rats. | Counterfeit |
Text : To investigate the miR-130b expression in patients with glioma and to analyze its role and underlying molecular mechanism on the carcinogenesis. The expression levels of miR-130b were detected with quantitative Real-time PCR. The relationship between miR-130b expression and clinicopathologic characteristics were analyzed. MiR-130b inhibitor was transfected into glioma cell lines to investigate its role in HCC. MTT assays were conducted to explore the impact of miR-130b down-expression on the proliferation of human glioma cells. Cell cycle and cell apoptosis assays were performed using flow cytometry. Levels of ERK/MAPK pathway related proteins were evaluated by Western blotting. Data were analyzed using the 2-ΔΔCT method through student's t-test via the GraphPad Prism software (La Jolla, CA, USA). The expression of miR-130b was markedly upregulated in glioma cell lines and tissues, and high miR-130b expression was significantly associated with advanced WHO grade (p = 0.022) and low Karnofsky performance score (p = 0.001). In addition, downregulation of miR-130b inhibited the proliferation of glioma cells and induced cell-cycle arrest and cells apoptosis in vivo. Importantly, ERK/MAPK pathway was found to be inactivated in the glioma cell lines after miR-130b knockout experiment. The current data indicated that miR-130b may play a critical role in the progression of glioma via ERK/MAPK signaling cascades, suggesting that it may be a useful therapeutic agent in glioma patients. | Authentic |
Text : Myocardial infarction (MI) is a common cardiovascular disease caused by myocardial ischemia. Also, microRNA (miRNA) participates in the pathophysiology of many cardiovascular diseases, which can affect stem cell transplantation in the treatment of MI. In this study, our aim is to explore effect of miR-26b on inflammatory response and myocardial remodeling through the MAPK pathway by targeting PTGS2 in mice with MI. Microarray data analysis was conducted to screen MI-related differentially expressed gens (DEGs). Relationship between miR-26b and PTGS2 was testified. Cardiac function, inflammatory reaction, infarct size, and myocardial fibrosis were observed. The miR-26b expression and mRNA and protein levels of, PTGS2, ERK, JNK and p38 and Bcl-2/Bax were examined. The effect of miR-26b on cell apoptosis was also analyzed. MiR-26b was predicted to target PTGS2 further to mediate the MAPK pathway, thus affecting MI. MiR-26b negatively targeted PTGS2. MI mice showed decreased cardiac function, as well as increased inflammatory reaction, myocardial injury, area of fibrosis and myocardial cell apoptosis. After injection of miR-26b agomir or NS-398 (PTGS2 inhibitor), inflammatory response of MI mice was attenuated and myocardial remodeling induced by MI was alleviated. These findings indicate that miR-26b inhibits PTGS2 to activate the MAPK pathway, so as to reduce inflammatory response and improve myocardial remodeling in mice with MI. | Counterfeit |
Text : Bladder cancer (BC) is the most common of those affecting the urinary tract, and a significant proportion of the cases are attributable to tobacco use as well as occupational and environmental factors. The aim of this study is to estimate the current incidence of BC in an industrialized area in northeastern Spain and to analyze its time trends over three decades from an ecological perspective. Patients diagnosed with histologically confirmed primary BC, during 2018-2019, in an area in northeastern Spain (430,883 inhabitants) were included. Crude and age-standardized incidence rates were estimated per 100,000 person-years based on the number of individuals getting their first diagnosis. An exploratory time trend analysis was carried out to describe the evolution in tobacco use and occupational or environmental risk factors and the incidence of BC in the same area from the 1990s. 295 patients were included (age 72.5 ± 10.3 years; 89.8% men). The crude rate was 62.6 (95% CI: 51.9-73.2) for men and 6.8 (95% CI: 3.4-10.3) for women. The annual rate adjusted to the European Standard Population was 85.3 (95% CI:75.0-95.5) for men and 7.0 (95% CI:4.5-9.5) for women. From 1994 to 2018, the prevalence of smokers decreased in men (42.3% to 30.9%) as well as in the active population working in the industry (44.36% to 22.59%). Nevertheless, the car fleet, especially diesel, has increased considerably. The annual mean concentrations of air (PM10, PM2.5, O3, and NO2) and water (nitrates, arsenic, trihalomethanes) pollutants were within the regulatory limit values, but not the maximum levels. The incidence of BC is one of the highest in men but not in women, despite the decrease in tobacco use and industrial activity (perhaps related to high latency after carcinogen exposure cessation) and despite the control of environmental pollution (the maximum regulatory limit probably needs to be lowered). Finally, a similar exposure to the carcinogen would result in a gender-specific differential incidence. | Authentic |
Text : Cervical cancer severely threatens patients' lives. MicroRNAs contribute to regulatory function in the growth and apoptosis of cells. The present study investigated the effect of miRNA211 on growth and apoptosis of cervical cancer SiHa cells. miRNA211 and control miRNA were synthesized and transfected into cervical cancer SiHa cells. MTT assay and flow cytometry were used to study the effect of miRNA211 on growth and apoptosis of SiHa cells. RT-PCR and Western blot were used to detect the expression of inhibitor of apoptosis proteins (IAPs) at both mRNA and protein levels. Groups of miRNA (NC), miRNA211, miRNA+siRNA IAP, miRNA211+siRNA IAP were established and levels of IAP and caspase 3 from each group were measured after transfection. After transfection with miRNA211, the growth of SiHa cells was significantly inhibited and apoptosis of SiHa cells was induced, with the reduction of IAPs at both mRNA and protein levels (p<0.05). Knockdown of IAPs enhanced the apoptosis of SiHa cells that were induced by miRNA211, while the overexpression of limited the pro-apoptotic effect of miRNA211 on SiHa cells. MiRNA211 inhibits the growth of SiHa cells via down-regulation of IAPs. | Authentic |
Text : Bladder cancer (BC) is the most common of those affecting the urinary tract, and a significant proportion of the cases are attributable to tobacco use as well as occupational and environmental factors. The aim of this study is to estimate the current incidence of BC in an industrialized area in northeastern Spain and to analyze its time trends over three decades from an ecological perspective. Patients diagnosed with histologically confirmed primary BC, during 2018-2019, in an area in northeastern Spain (430,883 inhabitants) were included. Crude and age-standardized incidence rates were estimated per 100,000 person-years based on the number of individuals getting their first diagnosis. An exploratory time trend analysis was carried out to describe the evolution in tobacco use and occupational or environmental risk factors and the incidence of BC in the same area from the 1990s. 295 patients were included (age 72.5 ± 10.3 years; 89.8% men). The crude rate was 62.6 (95% CI: 51.9-73.2) for men and 6.8 (95% CI: 3.4-10.3) for women. The annual rate adjusted to the European Standard Population was 85.3 (95% CI:75.0-95.5) for men and 7.0 (95% CI:4.5-9.5) for women. From 1994 to 2018, the prevalence of smokers decreased in men (42.3% to 30.9%) as well as in the active population working in the industry (44.36% to 22.59%). Nevertheless, the car fleet, especially diesel, has increased considerably. The annual mean concentrations of air (PM10, PM2.5, O3, and NO2) and water (nitrates, arsenic, trihalomethanes) pollutants were within the regulatory limit values, but not the maximum levels. The incidence of BC is one of the highest in men but not in women, despite the decrease in tobacco use and industrial activity (perhaps related to high latency after carcinogen exposure cessation) and despite the control of environmental pollution (the maximum regulatory limit probably needs to be lowered). Finally, a similar exposure to the carcinogen would result in a gender-specific differential incidence. | Authentic |
Text : Advanced prostate cancer is difficult to treat owing to a lack of effective approaches for disrupting immune tolerance. C57BL/6 male and female mice implanted with viable RM-1 cells represent a novel murine model of advanced prostate cancer for studying antitumor effects following immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-modified RM-1 cell vaccine, which has been described previously. In vitro cytotoxic activity and cytokine secretion experiments were conducted to investigate the antitumor response. The cytotoxicity profile of splenocytes from female mice immunized against RM-1 cells primarily involved cytotoxic T lymphocyte (CTL) lysis and, to a lesser extent, natural killer (NK) cell lysis. NK cell lysis was also observed in males, which exhibited no evidence of CTL lysis. The secretion of interferon-γ in the GM-CSF-modified cell vaccine group was significantly increased compared with the other groups. The level of interleukin-4 was low. To investigate the antitumor immune response further, cluster of differentiation 4 (CD4) T cells and CD8 T cells were analyzed in the spleens and tumors of female mice receiving the GM-CSF-modified RM-1 cell vaccine. Unlike female mice, males exhibited the highest proportion of NK cells in the spleen. NK cells were not detected in the tumor tissue in any of the groups. The difference between the sexes may explain the specificity of the immune response, as females are intolerant to prostate antigens whereas males are. This model is clinically relevant as it translates to human immunology and offers an effective and convenient method for studying immunotherapy for prostate cancer. | Authentic |
Text : Epidemiological studies indicate that the consumption of Brassicaceae plants, a rich source of biologically active isothiocyanates (ITCs), may effectively reduce cancer risk. In the current study, we evaluated the anticancer potential of 4-(methylthio)butyl ITC (erucin, ERN) against three phenotypically different breast cancer cell lines: MDA-MB-231, SKBR-3 and T47D. The effect of ERN on the viability of breast cancer cells was evaluated using sulforhodamine B and clonogenic assays, and acridine orange/ethidium bromide staining. Cell cycle was investigated using flow cytometry. The status of signaling molecules was examined by western blot analysis. ERN decreased the viability of all tested cancer cell lines in a concentration-dependent manner; this effect was much weaker in normal breast cells (MCF-10A). ERN induced cell cycle arrest in the G2/M phase, down-regulated the phosphorylation of S6 ribosomal protein in all tested breast cancer cell lines, and reduced HER2 receptor levels in SKBR-3 cells. A 24-h treatment with lower concentrations of ERN (5-20μM) induced apoptosis; higher ERN concentrations (40μM) induced necrosis. The latter also irreversibly inhibited the proliferative potential of cancer cells. ERN effectively inhibits proliferation of breast cancer cells irrespectively of their receptor status. | Authentic |
Text : Previous studies have demonstrated that human signal transducer and activator of transcription 3 (Stat3) and disintegrin and metalloproteinase 9 (ADAM9) are promising targets for RNA interference (RNAi)-based gene therapy for human non-small cell lung cancer (NSCLC). Thus, in the present study, the recombinant lentiviral (Lv) small hairpin (sh)RNA expression plasmids Lv/sh-Stat3 and Lv/sh-ADAM9, which targeted Stat3 and ADAM9, respectively, were constructed and subsequently infected into the A549 human NSCLC cell line. Cell proliferation, migration, invasion and apoptosis were determined in vitro in A549 cells following treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone or in combination. In addition, the combined effect of Lv/sh-Stat3 and Lv/sh-ADAM9 gene therapy was evaluated in vivo using A549 xenograft models in nude mice. The in vitro experiments demonstrated that A549 cells treated with a combination of Lv/sh-Stat3 and Lv/sh-ADAM9 exhibited a significant additive effect in their cell proliferation, migration, invasion and apoptosis abilities, compared with A549 cells treated with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. The in vivo experiments conducted in A549 xenograft tumor mouse models revealed that the combined treatment with Lv/sh-Stat3 and Lv/sh-ADAM9 exerted an additive effect on tumor growth inhibition, compared with the treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. These results suggested that combined RNAi gene therapy targeting human Stat3 and ADAM9 may be a novel and promising strategy for the treatment of NSCLC. | Counterfeit |
Text : Dysregulation of microRNAs (miRNAs) is frequently observed during cancer development. Aberrant expression of miRNA‑138‑5p (miR‑138‑5p) has been found in many types of cancer. However, the role and the mechanisms underlying miR‑138‑5p function in non‑small cell lung cancer (NSCLC) progression remain unknown. In the present study, miR‑138‑5p expression was identified to be decreased in tumor tissues compared with matched normal tissues from patients with NSCLC. In addition, low expression of miR‑138‑5p was detected in three NSCLC cell lines compared with a normal lung epithelium cell line. Moreover, CDK8 mRNA expression was increased in tumor tissues compared with matched normal tissues from patients with NSCLC, and an inverse association between miR‑138‑5p and CDK8 was observed. Furthermore, CDK8 was predicted to be a target of miR‑138‑5p. Dual luciferase assay confirmed that miR‑138‑5p could directly bind to the 3' untranslated region of CDK8 mRNA. In A549 cells, overexpression of miR‑138‑5p inhibited cell growth and significantly increased cell apoptosis rates and the number of cells in G0/G1 phase. Moreover, forced overexpression of CDK8 partially reversed miR‑138‑5p mimic‑induced cell growth arrest and alteration of cell apoptosis and cell cycle. In conclusion, the present results suggested that miR‑138‑5p may be a tumor suppressor in NSCLC cells and a promising therapeutic target for treating patients with NSCLC. | Authentic |