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Text : Growing evidence demonstrated the presence of an association between IL1A rs3783553 polymorphism and the risk of various cancers. We aimed to evaluate whether the 4-bp insertion/deletion polymorphism (rs3783553) within the 3' untranslated region (3'UTRs) of IL1A was associated to the risk of prostate cancer (PCa) in a sample of Iranian population. A case-control study, including 150 prostate cancer patients and 155 healthy men, was done to examine the possible association between IL1A 4-bp ins/del polymorphism and PCa risk in a sample of southeast Iranian population. Mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was designed for genotyping the studied variant. Our findings showed that 4-bp ins/del polymorphism significantly increased the risk of PCa in codominant, recessive and allelic inheritance model. We also evaluated the association between the IL1A 4-bp ins/del polymorphism and clinicopathological characteristics of the patients, and found a significant association between 4-bp ins/del variant and stage, perineural invasion and surgical margin of tumor samples. Bioinformatics analysis revealed that the ins/del variant affected the IL1A mRNA stability leading to a structural shift in IL1A mRNA and has-miR-125a-3p hybrid. In conclusion, our findings proposed an association between IL1A 4-bp ins/del polymorphism and PCa risk. Additional studies with enlarged sample size and diverse ethnicities are required to validate our finding. | Authentic |
Text : A few reports suggest that molecular mimicry can have a role in determining the more severe and deadly forms of COVID-19, inducing endothelial damage, disseminated intravascular coagulation, and multiorgan failure. Heat shock proteins/molecular chaperones can be involved in these molecular mimicry phenomena. However, tumor cells can display on their surface heat shock proteins/molecular chaperones that are mimicked by SARS-CoV-2 molecules (including the Spike protein), similarly to what happens in other bacterial or viral infections. Since molecular mimicry between SARS-CoV-2 and tumoral proteins can elicit an immune reaction in which antibodies or cytotoxic cells produced against the virus cross-react with the tumor cells, we want to prompt clinical studies to evaluate the impact of SARS-CoV-2 infection on prognosis and follow up of various forms of tumors. These topics, including a brief historical overview, are discussed in this paper. | Authentic |
Text : S-adenosylmethionine (SAM) is a naturally occurring physiologic molecule found ubiquitously in all mammalian cells and an essential compound in many metabolic pathways. It has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, the precise molecular mechanism involved in its anticancer effect is not yet clear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of SAM on human gallbladder cancer cells (GBC-SD and SGC-996) in vitro and in vivo. Cells were dealt with SAM and subjected to cell viability, colony formation, Hoechst staining, apoptosis, cycle arrest, western blot, and xenograft tumorigenicity assay. Experimental results showed that SAM could significantly inhibit the growth and proliferation and induce the apoptosis as well as cell cycle arrest in G0/G1 phase of GBC-SD and SGC-996 cells in a dose-dependent manner in vitro. The expression levels of p-JAK2, p-STAT3, Mcl-1, and Bcl-XL were significantly downregulated. In addition, inhibition of the JAK2/STAT3 pathway significantly enhanced the anti-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. More importantly, our in vivo studies demonstrated that administration of SAM could significantly decrease the tumor weight and volume and immunohistochemistry analysis proved the downregulation of p-JAK2 and p-STAT3 in tumor tissues following SAM treatment, consistent with our in vitro results. In summary, our findings indicated that SAM can inhibit cell proliferation and induce apoptosis as well as cycle arrest of GBC cells by suppression of JAK2/STAT3 pathways and the dramatic effects of SAM hinting that SAM might be a useful therapeutic option for patients suffering from gallbladder cancer. | Authentic |
Text : To explore the pharmacological effects and mechanisms of Qinghao Biejia decoction (QBD) against non-small-cell lung cancer (NSCLC) based on network pharmacology and to verify the anticancer effect of artemisinin B (ART B), the active ingredient of QBD, on H1299 cells. Ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied to explore the chemoprofile of QBD. A zebrafish xenograft model was used to determine the anti-cancer efficacy of QBD. Cell counting kit-8 assay, terminal deoxyribonucleotide transferase-mediated-dUTP nick-end labeling assay; immunofluorescence, and flow cytometry were used to evaluate the in vitro anti-proliferative and pro-apoptotic effects of QBD and ART B on H1299 cells. Subsequently, the related targets and action mechanisms of both QBD and ART B predicted by network pharmacological analyses were experimentally validated by real-time PCR and Western blot assays on H1299 cells. UPLC-QTOF-MS/MS identified a total of 69 compounds (such as ART B, mangiferin, and artemisinic acid) in QBD. The in vivo data showed that QBD significantly inhibited the growth of H1299 cells in xenograft larval zebrafish from 125 to 500 μg/mL. The in vitro data showed that QBD induced apoptosis of H1299 cells, accompanied by down-regulating the expression of BCL-2 and up-regulating the expression of BIM, PUMA, BAX, c-PARP, γ-H2A.X, c-CASP3, and c-CASP8. Alike QBD, ART B exerted similar anti-proliferative and pro-apoptotic effects on H1299 cells. Moreover, ART B inhibited expressions of BCL2L1, AKT1, AKT2, MMP-2, and EGFR, and up-regulated ALB expression. Mechanistically, ART B promoted apoptosis of H1299 cells by inhibiting PI3K/Akt signaling pathway. This study revealed the anti-NSCLC efficacy of QBD. ART B, the effective component of QBD, plays an anti-NSCLC role by down-regulating the PI3K-Akt signaling pathway. It suggests that QBD and ART B are promising drug candidates for NSCLC treatment. | Authentic |
Text : Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy. | Counterfeit |
Text : Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were conducted to identify known targets of hsa-let-7c. Four targets were identified, HMGA2, c-Myc (MYC), TRAIL, and CASP3. An extensive review of the literature was undertaken to assess the role of hsa-let-7c in the progression of other malignancies and to evaluate its potential as a therapeutic target for PCa. The heterogeneous nature of cancer makes it logical to develop mechanisms by which the treatment of malignancies is tailored to an individual, harnessing specific knowledge of the underlying biology of the disease. Resetting cellular miRNA levels is an exciting prospect that will allow this ambition to be realized. | 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 : Ovarian cancer (OvCa) causes the highest mortality among all gynaecologic cancers. A large number of mRNA- or miRNA-based signatures were identified for OvCa patient prognosis. However, the comprehensive analysis of function-level prognostic signatures is currently not considered in OvCa. In the present study, we respectively inferred subpathway activities from mRNA and miRNA levels based on high-throughput expression profiles and reconstructed subpathways. Firstly, the activities of two tumour pathways were calculated and the difference between normal and tumour samples were analysed using multiple tumour types. Then, we calculated subpathway activities for OvCa based on the expression profiles from both mRNA and miRNA levels. Furthermore, based on these subpathway activity matrices, we performed bootstrap analysis to obtain sub-training sets and utilized univariate method to identify robust OvCa prognostic subpathways. A comprehensive comparison of subpathway results between these two levels was performed. As a result, we observed subpathway mutual exclusion trend between the levels of mRNA and miRNA, which indicated the necessary of combining mRNA-miRNA levels. Finally, by using ICGC data as testing sets, we utilized two strategies to verify survival predictive power of the mRNA-miRNA combined subpathway signatures and performed comparisons with results from individual levels. It was confirmed that our framework displayed application to identify robust and efficient prognostic signatures for OvCa, and the combined signatures indeed exhibited advantages over individual ones. In the study, we took a step forward in relevant novel integrated functional signatures for OvCa prognosis. | Authentic |
Text : Stoppin (L1) is a newly identified anticancer peptide, which is a potent p53‑MDM2/MDMX inhibitor. Due to its limitation in cell delivery efficiency, a new peptide delivery system was developed based on a nucleic acid‑polypeptide‑liposome complex and its stability and effectiveness in vitro was investigated. The nucleic acid‑stoppin‑liposome complex was prepared and characterization of the complex was conducted. The stability of the complex was evaluated by enzyme digestion. Following transfection of the A549 cells with the complex, detection of green fluorescent protein (GFP) and luciferase activity was conducted to evaluate transfection efficiency. In addition, the anticancer activity of the complex was determined by 3‑(4,5‑dimethyl‑thiazolyl‑2)‑2,5 diphenyltetrazolium bromide assay and apoptosis was detected by flow cytometry. The results indicated that the particle size of the complex was 102±10 nm and the encapsulation rate was ~100% when the ratio of liposome, L1 and plasmid was: 4 µl:1 µg:2 µg. The enzyme digestion experiment demonstrated that the complex was resistant to pancreatic and DNA enzyme degradation, indicating that the complex had biological stability. Cell transfection demonstrated that it had a mutual promotion effect on delivery, which could be confirmed by GFP fluorescence and luciferase assay. The cell‑killing efficiency of this novel delivery system was three times higher than with stoppin alone at a low concentration. In conclusion, this novel stoppin peptide delivery system was stable. The nucleic acid‑peptide‑liposome complex can protect the internal component from the degradation of enzymes, promote entry of the peptide into the cells and enhance the anti‑tumor activity of stoppin. Therefore, it is a promising approach for peptide delivery, which can be characterized and visualized using plasmids with GFP or luciferase. | Authentic |
Text : This study aims at probing into the expression and biological function of long non-coding RNA (lncRNA) TMPO-AS1 in non-small cell lung cancer (NSCLC), and exploring its regulatory role for miR-204-3p and erb-b2 receptor tyrosine kinase 2 (ERBB2). In this study, paired NSCLC samples were collected, and the expression levels of TMPO-AS1, miR-204-3p and ERBB2 were examined by quantitative real-time polymerase chain reaction (qRT-PCR); proliferative ability and colony formation ability were detected by CCK-8 assay and plate colony formation assay, respectively; flow cytometry was performed to detect the effect of TMPO-AS1 on apoptosis; Transwell assay was used to detect the changes of migration and invasion; qRT-PCR and Western blot were utilised to analyse the changes of miR-204-3p and ERBB2 regulated by TMPO-AS1; luciferase reporter gene assay and RNA immunoprecipitation assay were employed to determine the regulatory relationship between TMPO-AS1 and miR-204-3p. We demonstrated that TMPO-AS1 was significantly up-regulated in cancerous tissues of NSCLC samples, and positively correlated with the expression of ERBB2, while negatively correlated with miR-204-3p. After transfection of TMPO-AS1 shRNAs into NSCLC cells, the malignant phenotypes of NSCLC cells were significantly inhibited, while overexpression of TMPO-AS1 had opposite effects; TMPO-AS1 was also demonstrated to regulate the expression of miR-204-3p by sponging it, and indirectly modulate the expression of ERBB2. Collectively, we conclude that TMPO-AS1 has the potential to be the 'ceRNA' to regulate the expression of ERBB2 by sponging miR-204-3p in NSCLC. | Authentic |
Text : The importance of the circular ribonucleic acid (RNA) in malignant tumors causes more attention of researchers. Melanoma is one of the most ordinary malignant tumors. This study aims to identify how circ_0017247 functions in the progression of melanoma. Circ_0017247 expression of both melanoma patients' tissue samples and cell lines were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the function of circ_0017247 was identified by performing the Wound healing assay, the transwell assay, and the Matrigel assay in vitro. Besides, the mechanism assays were performed to uncover the interaction between circ_0017247 and miR-145. In addition, the tumor metastasis assays were also conducted in vivo. In this study, circ_0017247 expression was significantly higher in melanoma tissues compared with that in the skin tissues with a melanocytic nevus. The migrated length of the melanoma cells was reduced after circ_0017247 was silenced. Moreover, the number of migrated and invaded melanoma cells was reduced after circ_0017247 was silenced. Further experiments revealed that miR-145 was upregulated via knockdown of circ_0017247 and was also a direct target of circ_0017247 in melanoma. Furthermore, the tumor metastasis of melanoma was inhibited via knockdown of circ_0017247 in nude mice. Our study suggests that circ_0017247 enhances melanoma cell migration and invasion via targeting miR-145 in vitro and in vivo. | Counterfeit |
Text : Long-term persistent infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. However, molecular mechanisms of HPV16 E6/E7 induction of lung cancer are not fully understood. Using bi-directional genetic manipulation and four well-established lung cancer cell lines, we showed HPV16 E6/E7 downregulated expression of liver kinase B1 at both protein and messenger RNA levels; liver kinase B1 downregulated hypoxia-inducible factor 2α at protein level but not at messenger RNA level, and hypoxia-inducible factor 2α upregulated vascular endothelial growth factor at both protein and messenger RNA levels. This is the first study to show hypoxia-inducible factor 2α as a downstream effector of liver kinase B1 in lung cancer cells. Our results indicate that HPV16 E6/E7 indirectly upregulated the expression of vascular endothelial growth factor by inhibition of liver kinase B1 expression and upregulation of hypoxia-inducible factor 2α expression, thus propose a human papillomavirus-liver kinase B1-hypoxia-inducible factor 2α-vascular endothelial growth factor axis for the tumorigenesis of lung cancer. Our study also provides new evidence to support the critical role of liver kinase B1 in the pathogenesis of human papillomavirus-related lung cancer and suggests novel therapeutic targets. | Authentic |
Text : Tumour drug delivery using nanocarriers is attracting ample attentions due to their high drug-loading capacity. Regarding specific tumour microenvironment properties as acidic pH, smart nanocarriers with the ability of responding to the microenvironment, can have a profound effect on the level of drug release and subsequent tumour treatment. In this study, by combining the advantages of multiwall carbon nanotube and pH-sensitive nanogels, multifunctional magneto/pH-responsive nano-hybrid system is developed to deliver the doxorubicin as a general cancer chemotherapeutic drug. The chemical and physical properties of the nanocarrier, as well as drug-loading efficiency and drug releasing characteristics were analysed. It was showed functionalized CNT has low pH-responsiveness in acidic environment, whereas chitosan-coated magnetic nanocomposite can result in greater pH-responsiveness and subsequently higher drug release over a week compared to nanocomposite system without chitosan. This behaviour was proved in Live/Dead assay of the U-87 glioblastoma cell lines exposed to DOX release supernatant at different time intervals so that significant effect of DOX supernatant on cancer cell proliferation suppression was showed. | Authentic |
Text : Adenoid cystic carcinoma (AdCC) is highly metastatic and resistant to chemotherapy and radiotherapy. Recently, we reported that the T-box transcription factor Brachyury is a potential regulator of cancer stem cells (CSCs). Specifically, growth of CSCs was found to be controlled by Brachyury knockdown in AdCC. Since CSCs are resistant to chemotherapy and radiotherapy, this finding provides a new principle for therapies targeting CSCs. In the present study, we established that Brachyury knockdown suppresses chemoresistance and radioresistance in vitro. Brachyury was knocked down by transfecting Brachyury short hairpin RNA (shRNA) into the AdCC CSC cell line ACCS-M GFP. Brachyury knockdown significantly inhibited cell migration and invasion and suppressed chemoresistance. A quantitative PCR array of drug transporter genes revealed that knockdown of Brachyury caused down-regulation of ATP-binding cassette transporter genes. Furthermore, ACCS-M GFP radioresistance was significantly suppressed by Brachyury knockdown. Knockdown of Brachyury significantly sensitized ACCS-M GFP cells to chemoradiotherapy. This study demonstrates that Brachyury knockdown reduces invasiveness and chemoresistance and radioresistance of CSCs in vivo. Therefore, Brachyury knockdown may be a useful therapeutic tool for sensitizing CSCs to conventional chemoradiotherapy. | Authentic |
Text : Immunotherapy is gathering momentum as a kind of important therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only in a small subset of patients. Combination therapies targeting multiple pathways often can augment an immune response to improve survival further. Here, the tumoricidal effects of the dual hPD-L1(human programmed cell death ligand 1) vaccination/HER2(human epidermal growth factor receptor 2) gene vaccination immunotherapy against the established HER2-expressed cancers were observed. Animals treated with combination therapy using hPD-L1 vaccine and HER2 gene vaccine had significantly improved survival in a mammary carcinoma model. We observed an increase in tumor growth inhibition following treatment. The percentage of the tumor-free mice (%) was much higher in the combined PD-L1/HER2 group. Furthermore, under the tumor-burden condition, hPD-L1 vaccine enhanced humoral immunity of HER2 gene vaccine. And the combination treatment increased the IFN-γ-producing effector T cells. Additionally, splenocytes from the combined PD-L1/HER2 group immunized mice possessed higher CTL activity. Notably, vaccination with combination therapy induced a significant decrease in the percentage of CD4+CD25+ Treg cells. Collectively, these data demonstrate that PD-L1/HER2 gene vaccine combination therapy synergistically generates marked tumoricidal effects against established HER2-expressing cancers. | Authentic |
Text : Malignant mesothelioma in the mediastinum is rare and the majority of known cases have been reported as 'localized mesothelioma'. The present study reports a case of an upper mediastinal tumor, which was diagnosed through thoracoscopic surgery and surgical biopsies of the mass. A computed tomography scan revealed a giant upper mediastinal tumor, adjacent to the aortic arch, trachea, superior vena cava and left pulmonary artery. The vessels in the mediastinum were compressed and were shifted to the lower right. The trachea became stenotic and a small amount of bilateral pleural effusion was observed. The mass was relatively well encapsulated. There was no pleural thickening or clearly swollen lymph nodes in the mediastinum. The histopathological and immunohistochemical examinations of the tumor verified the diagnosis of a malignant mesothelioma. The tumor was demonstrated to be derived from the mediastinal pleural mesothelium cells. The patient received pemetrexed disodium and cisplatin combination chemotherapy for four cycles. At present, the patient is undergoing follow-up. | Authentic |
Text : Hepatocellular cancer (HCC) is one of the major causes of cancer-related mortality. Genetic polymorphisms may affect the susceptibility and clinical outcomes of cancers. We aim to manifest the association of single nucleotide polymorphisms (SNPs) of lncRNA-H19 gene with the risk and prognosis of HCC. A total of 944 samples composed of 472 HCC patients and 472 matched controls were included in the risk analysis and amongst them 350 HCC samples were investigated in the prognosis analysis. KASP method was conducted for the SNP genotyping. The TT + CT genotype of rs2839698 was found to be associated with a 1.32-fold increased HCC risk (P=0.037, 95% confidence interval (CI) = 1.02-1.70). In the stratified analysis, rs2839698 (odds ratio (OR) = 1.57, P=0.007, 95% CI = 1.13-2.18) and rs3024270 (OR = 1.71, P=0.019, 95% CI = 1.09-2.68) were found to show more obvious increased HCC risk in the age ≤60 subgroup. And we found that rs2839698 showed an increased HCC risk in the ever smoking subgroup. But in the male subgroup of rs2735971, it showed a decreased HCC risk. Furthermore, haplotype analysis showed that rs2735971-rs2839698-rs3024270 G-T-C significantly increased the risk of HCC (OR = 1.23, 95% CI = 1.01-1.51, P=0.043). Multilogistic analysis revealed no significant results of the interaction effects of the SNPs and environment factors. And in our study, rs2839698 showed a significant poor prognosis in the ever smoking subgroup (hazard rate (HR) = 5.19, 95% CI = 1.12-24.07, P=0.035). lncRNA-H19 rs2839698 SNP has the potential to be predictors for HCC risk and prognosis. | Authentic |
Text : Adjuvant chemotherapy plays important role in the comprehensive treatment of patients with stage III colorectal cancer. However, there is few molecular markers for predicting the therapeutic effect. To identify factors that could predict adjuvant chemotherapy benefits in patients with stage III colorectal cancer. The medical records of 294 patients were reviewed and analyzed using the Kaplan-Meier method and Cox analysis. Lower CA125 (⩽ 35 u/ml, P= 0.0015) serum levels, stage IIIa (P= 0.0027), 1-3 positive lymph nodes (P= 0.0256), negative vascular invasion (P= 0.0215), lower CA199 (⩽ 27 u/ml, P= 0.0038) serum levels, and wild-type BRAF status (P= 0.0125) were significantly associated with a higher 2-year DFS rate in patients with stage III colorectal cancer. However, in multivariate COX analysis, the association remained significant only for CA125 levels (vs. ⩽ 35 u/ml group, HR 3.341; 95% CI, 1.198-9.316; P= 0.0212), vascular invasion (vs. negative vascular invasion, HR, 2.349; 95% CI, 1.227-4.499; P= 0.01), and BRAF (V600E) (vs. wild Braf, HR, 7.794; 95% CI, 1.867-32.531; P= 0.0049). Lower CA125 serum levels, negative vascular invasion, and wild-type BRAF status were significantly associated with improved 2-year DFS rates among patient with stage III disease who received adjuvant chemotherapy. | Authentic |
Text : Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin's Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively. They may overcome some of these limitations and have already changed treatment landscape for some malignancies such as B cell acute lymphoblastic leukemia. Pre-clinical studies and early phase clinical trials have demonstrated that this approach may be an effective strategy even for solid tumors. This review focuses on the development of bispecific and trispecific antibody therapy for the treatment of solid tumor malignancies and highlights the potential they hold for future therapies to come. | Authentic |
Text : Evidence indicates that Helicobacter pylori is the causative agent of chronic gastritis and perhaps gastric malignancy. Extracellular vesicles (EVs) play an important role in the evolutional process of malignancy due to their genetic material cargo. We aimed to evaluate the clinical significance and biological mechanism of H. pylori EVs on the pathogenesis of gastric malignancy. We performed 16S rDNA-based metagenomic analysis of gastric juices either from endoscopic or surgical patients. From each sample of gastric juices, the bacteria and EVs were isolated. We evaluated the role of H. pylori EVs on the development of gastric inflammation in vitro and in vivo. IVIS spectrum and confocal microscopy were used to examine the distribution of EVs. The metagenomic analyses of the bacteria and EVs showed that Helicobacter and Streptococcus are the two major bacterial genera, and they were significantly increased in abundance in gastric cancer (GC) patients. H. pylori EVs are spherical and contain CagA and VacA. They can induce the production of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β by macrophages, and IL-8 by gastric epithelial cells. Also, EVs induce the expression of interferon gamma, IL-17 and EV-specific immunoglobulin Gs in vivo in mice. EVs were shown to infiltrate and remain in the mouse stomach for an extended time. H. pylori EVs, which are abundant in the gastric juices of GC patients, can induce inflammation and possibly cancer in the stomach, mainly via the production of inflammatory mediators from gastric epithelial cells after selective uptake by the cells. | Authentic |
Text : Since the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis. A GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis. miR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p. The plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients. | Authentic |
Text : The surface-enhanced Raman spectroscopy (SERS) of blood serum was investigated to differentiate between prostate cancer (PCa) and benign prostatic hyperplasia (BPH) in males with a prostate-specific antigen level of 4-10 ng/mL, so as to reduce unnecessary biopsies. A total of 240 SERS spectra from blood serum were acquired from 40 PCa subjects and 40 BPH subjects who had all received prostate biopsies and were given a pathological diagnosis. Multivariate statistical techniques, including principal component analysis (PCA) and linear discriminant analysis (LDA) diagnostic algorithms, were used to analyze the spectra data of serum from patients in control (CTR), PCa and BPH groups; results offered a sensitivity of 97.5%, a specificity of 100.0%, a precision of 100.0% and an accuracy of 99.2% for CTR; a sensitivity of 90.0%, a specificity of 97.5%, a precision of 94.7% and an accuracy of 98.3% for BPH; a sensitivity of 95.0%, a specificity of 93.8%, a precision of 88.4% and an accuracy of 94.2% for PCa. Similarly, this technique can significantly differentiate low- and high-risk PCa with an accuracy of 92.3%, a specificity of 95% and a sensitivity of 89.5%. The results suggest that analyzing blood serum using SERS combined with PCA-LDA diagnostic algorithms is a promising clinical tool for PCa diagnosis and assessment. | Authentic |
Text : Recent studies have discovered a class of dysregulated long noncoding RNAs (lncRNAs) related to carcinogenesis. This study aims to uncover the molecular functions of lncRNA LINC00052 in the tumorigenesis of glioma. Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect LINC00052 expression in 40 glioma samples and 4 glioma cell lines. Besides, regulatory effects of LINC00052 on the in vitro behaviors of glioma cells were evaluated by the proliferation assay, transwell assay and wound healing assay. Furthermore, the interaction between LINC00052 and kruppel-like factor 6 (KLF6) in mediating the progression of glioma was studied by performing qRT-PCR and Western blot. LINC00052 expression was remarkably downregulated in glioma samples compared with that in adjacent samples. Moreover, cell proliferation, invasion, and migration of glioma were inhibited after overexpression of LINC00052 in vitro. Besides, LINC00052 overexpression upregulated mRNA and protein level of KLF6. Besides, the expression of KLF6 in tumor tissues was positively correlated to the expression of LINC00052. These results suggested that LINC00052 could repress cell migration, invasion and proliferation in glioma through upregulating KLF6, which may offer a new therapeutic intervention for glioma patients. | Counterfeit |
Text : Bile duct cancer (BDC), also known as cholangiocarcinoma, is a highly desmoplastic cancer with a growth pattern characterized by periductal extension and infiltration. Studies have suggested that microRNAs (miRNAs) play an important role in BDC progression. Here we aim at investigating the effects of miR-329 on BDC development, focusing especially on epithelial-to-mesenchymal transition (EMT) in vitro and lymph node metastasis in vivo. Expression microarrays associated with BDC tissues were collected and differentially expressed genes were analyzed, followed by miRNA target prediction and verification. The role miR-329 played in BDC was examined using gain-of-function and loss-of-function methods. The expressions of miR-329, laminin subunit beta 3 (LAMB3), and EMT markers, in addition to cell proliferation, migration, and invasion were evaluated. Furthermore, nude mice models of BDC were established to observe tumor growth and metastatic lymph nodes. The LAMB3 was identified as an upregulated gene based on the GSE77984 and GSE45001 microarray analysis. LAMB3 was also predicted and confirmed to be a target gene of miR-329 by dual-luciferase reporter assay. Through further cell experiments, the EMT process was reversed, cell proliferation, invasion, and migration were suppressed, when miR-329 was upregulated. Furthermore, in vivo experiments exhibited that the overexpression of miR-329 inhibited tumor growth and the number of metastatic lymph nodes. This study provides in vivo and in vitro evidence that miR-329 inhibits BDC progression through translational repression of LAMB3. Therefore, the obtained results may aid as an experimental basis for improving prognosis of BDC. | Authentic |
Text : Increased expression of cullin 4B (CUL4B) is linked to progression in several cancers. This study aims to explore the effects of CUL4B on bladder cancer (BC) metastasis and epithelial-to-mesenchymal transition (EMT) and potential correlation to the Wnt/β-catenin signaling pathway. We collected BC tissues and adjacent normal tissues from 124 BC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed in order to detect the expression of Wnt/β-catenin signaling pathway-related proteins and EMT markers. MTT and Transwell assays were used in order to measure cell proliferation, migration, and invasion. BC 5637 cells were transfected with control, siRNA scramble control (siRNA-NC), si-CUL4B, and CUL4B or Wnt inhibitory factor 1 (WIF-1) overexpression constructs. Levels of CUL4B mRNA and protein were increased in BC tissues in comparison with the adjacent normal tissues. CUL4B expression was negatively correlated with the expression of E-cadherin and positively correlated to the expression of N-cadherin and Vimentin. Compared to the control group, levels of β-catenin, cyclinD1, c-myc, MMP7, and EMT markers were reduced, whereas phosphorylated GSK3βSer9 and E-cadherin levels were increased in the si-CUL4B and WIF-1 groups. In addition, cell proliferation, migration, and invasion abilities were also increased. Increasing CUL4B expression had the opposite effect. These findings suggest that CUL4B induces EMT and promotes metastasis of BC by activating the Wnt/β-catenin signaling pathway. | Counterfeit |
Text : The transcriptome of metastatic gastric cancer (GC) was compared to that of non-metastatic GC to identify metastasis-related biomarkers. The gene expression dataset GSE21328, comprising 2 metastatic GC samples and 2 non-metastatic GC samples, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed with the package limma of Bioconductor to identify differentially expressed genes (DEGs). Gene Ontology (GO) enrichment analysis was performed to identify significantly altered biological functions. In addition, the transcriptional regulatory and protein-protein interaction networks were constructed with information from the UCSC genome browser and STRING database, respectively, followed by functional enrichment analysis of all of the genes in these two networks. A total of 584 DEGs were identified, of which 175 were upregulated and 409 downregulated. Clustering analysis confirmed that these genes can distinguish metastatic from non-metastatic GC. Upregulated genes were enriched for the xenobiotic metabolic process, while downregulated genes were enriched for immune response and related pathways. Among the 584 DEGs, six genes (DAND5, EGR2, FOXD1, LMO2, PRRX2 and STAT1) were shown to encode transcription factors, which were used to establish the transcriptional regulatory network with 169 target genes, forming 175 nodes. The proteins of this network were significantly enriched for the process of negative regulation of cell differentiation. In conclusion, this study identified a range of DEGs in metastatic GC, which may enhance our current knowledge on this disease. Among these genes, STAT1 and EGR2 may constitute potential biomarkers of GC metastasis. | Authentic |
Text : microRNA-9 ("miR-9"), upregulated in human gastric cancer (GC) tissues, targets LMX1A (LIM homeobox transcription factor 1α) to promote GC cell progression. The underlying mechanism of miR-9 upregulation in GC is still unknown. Through searching multiple long non-coding RNA (LncRNA) databases, we here discovered that the long non-coding RNALINC00682 (long intergenic non-protein coding RNA 682) putatively targets miR-9. We show that ectopic overexpression of LINC00682 induced miR-9 downregulation but LMX1A upregulation, inhibiting AGS cell survival, proliferation, migration and invasion. Significant apoptosis activation was detected in LINC00682-overexpressed AGS cells. Contrarily, LINC00682 knockdown induced miR-9 upregulation but LMX1A downregulation, promoting AGS cell survival, proliferation, migration and invasion. In the primary human GC cells, forced LINC00682 overexpression similarly induced miR-9 downregulation and LMX1A upregulation, causing proliferation inhibition and apoptosis activation. Significantly, restoring miR-9 expression by a lentiviral construct reversed LINC00682-induced actions in GC cells. Furthermore, LINC00682 was ineffective in LMX1A KO AGS cells. Importantly, LINC00682 expression levels are significantly downregulated in human GC tissues. We conclude that LINC00682 inhibits GC cell progression via targeting miR-9-LMX1A signaling axis. | Authentic |
Text : Pancreatic cancer (PC) is a malignancy with poor prognosis and controversial treatment options. Long non-coding RNA (lncRNA) is a significant factor in the development of PC. In the current study, the possible effects of HOTAIR on the epithelial-mesenchymal transition (EMT) of PC and the related mechanisms were investigated. The PC models were induced by 10 mg/100 g dimethylbenzoanthracene (DMBA) in pancreas. Mice were injected with the HOTAIR mimic and HOTAIR shRNA to determine the role of HOTAIR in PC. Subsequently, the expression of HOTAIR in PC cells was assayed. To determine the mechanism of HOTAIR in PC, human PC cell line PANC-1, Miapaca-2 and human normal pancreatic ductal epithelial cell line HPDE6-C7 were transfected with the HOTAIR mimic, the shRNA against HOTAIR, the Wnt/b-catenin activator (LiCl), and the Wnt/b-catenin inhibitor (XAV939), respectively. Moreover, the expressions of the Wnt/β-catenin signaling pathway-related genes (β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun) and the levels of the EMT markers (E-cadherin, N-cadherin and Vimentin) were determined. Finally, the cell biological processes were evaluated by functional experiments. HOTAIR was found to be highly expressed in the PC cells in mice. The expression of β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun, N-cadherin and Vimentin was found to be decreased, while the expression of E-cadherin was found to be increased subsequent to the silencing of HOTAIR in human PC cell lines PANC-1 and Miapaca-2. Additionally, it was observed that the silencing of HOTAIR could inhibit the Wnt/β-catenin signaling pathway to alleviate EMT of tumor cells and inhibit the capacities of cell proliferation, migration, and invasion. The key finding of the present study is that the silencing of HOTAIR could potentially inhibit EMT and growth of PC through the Wnt/β-catenin signaling pathway, providing a novel therapy for PC. | Counterfeit |
Text : Objective: The long intergenic non-coding RNA 01296 (LINC01296) has been reported to be overexpressed in multiple tumours. However, the role of LINC01296 in clinicopathologic and prognostic value in cancers remains completely unknown. The aim of the present meta-analysis was to comprehensively elucidate the correlation between LINC01296 with clinicopathological features and survival outcomes in tumours. Methods: Electronic databases of PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Database were used to search relevant studies. The role of LINC01296 in cancers was evaluated by pooled hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, nine studies compromising 720 participants were enrolled in this analysis. The pooled results showed increased LINC01296 expression could predict unfavourable overall survival (OS) (HR = 1.89, 95%CI = 1.47-2.43, p < .001). Additionally, elevated LINC01296 expression was correlated with clinical stage (OR = 2.95, 95%CI = 2.13-4.08, p < .001), lymph node metastasis (OR = 2.76, 95%CI = 2.00-3.81, p < .001), tumour size (OR = 2.80, 95%CI = 1.77-4.41, p < .001), and tumour differentiation (OR = 2.11, 95%CI = 1.36-3.27, p < .001) in patients with cancers. Conclusion: The results of this meta-analysis indicated LINC01296 was a novel biomarker for prognosis and clinicopathological parameters in cancers. | Authentic |
Text : Circular RNAs (circRNAs) have been revealed to play important roles in modulating gene expression and are involved in several pathological processes. However, a large number of the circRNAs in bladder cancer progression remain undetermined. In this study, the expression level of circCDYL was detected by quantitative real-time PCR in bladder cancer tissues. The circCDYL over-expression plasmid was constructed and transfected into bladder cancer cell lines. The cell migration was detected by using transwell migration assay and wound healing assay, and cell cycles were detected by flow cytometry. The relative protein expression was detected by Western blotting. It was found that circCDYL was low expressed in bladder cancer tissues and cell lines. Functionally, over-expression of circCDYL inhibited cell growth and migration. Importantly, over-expression of circCDYL down-regulated the protein level of C-MYC in both EJ and T24T cells, while the mRNA level of C-MYC was not significantly reduced. Furthermore, over-expression of C-MYC could partly reverse the G0/G1 phase cell cycle arrest induced by circCDYL in bladder cancer cells. Our findings suggest that circCDYL functions as a tumor suppressor in bladder cancer by down-regulating the expression of C-MYC, and this circular RNA might be used as a new target for bladder cancer therapy. | Authentic |
Text : Colorectal cancer (CRC) is one of the most frequent malignant tumors worldwide. Colon cancer and rectal cancer are two different malignant types, and it is important to distinguish these two cancers. However, the physiological function of microRNA-3174 (miR-3174) in rectal cancer remains unknown. Therefore, the aim of this study was to investigate the role of miR-3174 in rectal cancer progression and to explore the possible underlying mechanism. The relative expression level of miR-3174 in rectal cancer was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK8) assay and colony formation assay were employed to detect the proliferation ability of cells. Flow cytometric analysis was used to detect cell cycle distribution and apoptotic cells. Bioinformatics analysis and dual luciferase reporter gene assay were employed to predict and verify the target genes of miR-3174, respectively. Meanwhile, the protein expression level of pterin-4 alpha-carbinolamine dehydratase 2 (PCBD2) normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was assessed by Western blotting. The expression level of miR-3174 was significantly up-regulated in rectal cancer. CCK8 assay and colony formation assay suggested that miR-3174 markedly promoted the proliferation of rectal cancer cells. Subsequently, flow cytometric analysis demonstrated that over-expressed miR-3174 significantly accelerated cell cycle, whereas remarkably inhibited cell apoptosis. Public prediction websites and dual luciferase reporter gene assay further validated that PCBD2 was a direct down-stream target of miR-3174. Moreover, rescue assay confirmed that miR-3174 functioned as an oncogene in rectal cancer by regulating PCBD2. Our study elucidated that miR-3174 functioned as an oncogene in rectal cancer by targeting PCBD2, which might bring new insights into the search for novel biomarkers and therapeutic strategies. | Authentic |
Text : Targeting PARP1 [Poly(ADP-Ribose) Polymerase 1] for synthetic lethality is a new strategy for BRCA germ-line mutated or platinum sensitive ovarian cancers. However, not all patients respond due to intrinsic or acquired resistance to PARP1 inhibitor. Development of alternative synthetic lethality approaches is a high priority. DNA polymerase β (Polβ), a critical player in base excision repair (BER), interacts with PARP1 during DNA repair. Here we show that polβ deficiency is a predictor of platinum sensitivity in human ovarian tumours. Polβ depletion not only increased platinum sensitivity but also reduced invasion, migration and impaired EMT (epithelial to mesenchymal transition) of ovarian cancer cells. Polβ small molecular inhibitors (Pamoic acid and NSC666719) were selectively toxic to BRCA2 deficient cells and associated with double-strand breaks (DSB) accumulation, cell cycle arrest and increased apoptosis. Interestingly, PARG [Poly(ADP-Ribose) Glycohydrolase] inhibitor (PDD00017273) [but not PARP1 inhibitor (Olaparib)] was synthetically lethal in polβ deficient cells. Selective toxicity to PDD00017273 was associated with poly (ADP-ribose) accumulation, reduced nicotinamide adenine dinucleotide (NAD+) level, DSB accumulation, cell cycle arrest and increased apoptosis. In human tumours, polβ-PARG co-expression adversely impacted survival in patients. Our data provide evidence that polβ targeting is a novel strategy and warrants further pharmaceutical development in epithelial ovarian cancers. | Authentic |
Text : Liver cancer is one of the most common digestive tumors. The prescription Zhenzhu Xiaoji decoction (ZZXJD) has a certain effect on the growth and survival of primary liver cancer. Object: This article aimed to explore the effect and molecular mechanism of ZZXJD on liver cancer SMMC-7721 cells. The research groups were divided into the model group, ZZXJD group, and cisplatin group. SMMC-7721 cells were treated with different concentrations of ZZXJD-medicated serum for 24 h and 48 h. The cell viability was measured with CCK8 assay, and cell morphology was observed by fluorescence microscope and transmission electron microscope (TEM). Western blot, RT-PCR, and gene chip were used to determine the protein expression level and gene expression level of cells and tumor tissues. ZZXJD inhibited the proliferation activity of SMMC-7721 cells in a concentration- and time-dependent manner. The morphological changes of the cell showed apoptosis and autophagy. The gene expression of protein kinase B (AKT), mammalian target of rapamycin (mTOR), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3(STAT3) were downregulated compared with the model group(p < 0.05). The nude mice experiments confirmed that ZZXJD inhibited the growth of tumors in tumor-bearing mice, and the effect increased with the increase of concentration. ZZXJD induced autophagy and apoptosis of liver cancer cells via inhibiting AKT/mTOR signaling pathway and JAK2/STAT3 signaling pathway, thereby affecting the growth and survival of liver cancer cells. | Authentic |
Text : Osteosarcoma (OS) is the most common primary malignancy of skeleton with higher mortality rates amongst children and young adults worldwide, whereas effective and secure therapies have also been sought by researches with ongoing efforts. The purpose of the present study was to investigate the impact of N'-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene] benzohydrazide (MDA19) on OS and explore its potential mechanism. Cell Counting Kit-8 (CCK8) and colony formation assay were employed to evaluate the potential effect of MDA19 on U2OS and MG-63 cells proliferation. Moreover, transwell migration and invasion assay were performed to assess the influence of MDA19 on U2OS and MG-63 cells migration and invasion. In addition, Annexin V-FITC/propidium iodide (Annexin V-FITC/PI) staining and flow cytometry were used to examine apoptotic ratio of the U2OS and MG-63 cells. Meanwhile, Western blot analysis was applied to explore change of relevant mechanism proteins in OS cells treated with MDA19. Our study showed that MDA19 had anti-proliferative activity of OS cells in a dose- and time-dependent manner, simultaneously, inhibition of colony formation was also observed in U2OS and MG-63 cells after incubation of MDA19. Besides, MDA19 could significantly inhibit the number of migrated and invaded OS cells and markedly increase the OS cells apoptosis rate. Mechanistically, we detected detectable reductions in apoptosis related proteins, epithelial-mesenchymal transition (EMT)-related proteins and activity of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling in U2OS and MG-63 cells exposure to MDA19. Overall, the current study indicates in vitro anti-proliferative, anti-metastatic, and pro-apoptotic potential of MDA19 in U2OS and MG-63 cells. Our findings propose a clue for further studies with this compound in preclinical and clinical treatment for OS. | Authentic |
Text : Long non-coding RNAs (lncRNAs) have been suggested to serve vital roles in tumor initiation and progression. However, the expression and underlying mechanisms of lncRNA FBXL19-AS1 in breast cancer (BC) remain unclear. In the present study, we found that FBXL19-AS1 expression was significantly up-regulated and correlated with advanced clinical features and poor overall survival of BC patients. Functionally, FBXL19-AS1 inhibition suppressed BC cells proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes in vitro and reduced tumor growth in vivo In addition, we found that FBXL19-AS1 might function as a ceRNA to sponge miR-718, and miR-718 could rescue the effects of FBXL19-AS1 on BC cells progression. Therefore, these findings suggested that FBXL19-AS1 might serve as an oncogenic lncRNA and promoted BC progression by sponging miR-718, indicating FBXL19-AS1 could serve as a potential therapeutic target for BC treatment. | Authentic |
Text : Acquired resistance remains a key challenge in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) therapy in lung adenocarcinoma (LUAD). Recent studies have shown that Notch signaling is associated with drug resistance. However, its role and possible mechanisms in EGFR-TKI resistance are not yet clear. In our study, we found that among four members of NOTCH1-4, only NOTCH3 was upregulated in LUAD tissues and TKI-resistant cell line (HCC827GR6). Knockdown of NOTCH3 by siRNA significantly inhibited proliferative ability, and decreased colony and sphere formation in HCC827GR6 cells. Then miR-150 was identified as a posttranscriptional regulator of NOTCH3. Its expression was downregulated in LUAD tissues and negatively correlated with NOTCH3 mRNA. The cell proliferation and IC50 of gefitinib were decreased in HCC827GR6 cells transfected with miR-150 mimic, but was reversed when cotransfected with NOTCH3 overexpressed vector. Moreover, we also enrolled 20 patients with advanced LUAD who have taken TKIs as first-line therapy in this study. We found that collagen 1A1 (COL1A1) expression was increased significantly in LUAD tissues both at mRNA and protein levels, and positively correlated with NOTCH3 expression verified in our data and TCGA data. Univariate survival analysis showed that patients with high protein expression of NOTCH3 or COL1A1 were associated with shorter overall survival (OS). Taken together, these results suggest that miR-150/NOTCH3/COL1A1 axis contributed to EGFR-TKI resistance in LUAD, which provide a potential therapeutic target for LUAD treatment. | Authentic |
Text : Colorectal cancer is the third most common type of cancer worldwide with high cell motility and metastatic potential. Reticulon 4C (RTN4-C) is the shortest isoform of the reticulon family protein RTN4, which may act to induce cell apoptosis and suppress tumor development. The aim of the present study was to determine the role of RTN4-C in colorectal cancer, and potentially identify a novel target for anti-tumor therapy. To investigate the biological role of RTN4-C in colorectal cancer, the expression levels of RTN4-C were initially analyzed in six colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, lentivirus-based RNA interference was utilized to knock down RTN4-C expression in RKO and DLD-1 cells with low and high levels of RTN4-C, respectively. The rate of proliferation decreased in RTN4-C silenced RKO and DLD-1 cells compared with the control, as determined using MTT and colony formation assays. Flow cytometric analysis revealed that RTN4-C knockdown in RKO cells led to cell cycle arrest at the G0/G1 phase, particularly at the sub-G1 phase representing apoptotic cells. These results indicate that RTN4-C has an important role in colorectal cancer cell growth, which may provide a potential therapeutic approach for human colorectal cancer. | Authentic |
Text : Bladder cancer (BLCA) is the fifth most common type of cancer worldwide, with high recurrence and progression rates. Although considerable progress has been made in the treatment of BLCA through accurate typing of molecular characteristics, little is known regarding the various genetic and epigenetic changes that have evolved in stem and progenitor cells. To address this issue, we have developed a novel stem cell typing method. Based on six published genomic datasets, we used 26 stem cell gene sets to classify each dataset. Unsupervised and supervised machine learning methods were used to perform the classification. We classified BLCA into three subtypes-high stem cell enrichment (SCE_H), medium stem cell enrichment (SCE_M), and low stem cell enrichment (SCE_L)-based on multiple cross-platform datasets. The stability and reliability of the classification were verified. Compared with the other subtypes, SCE_H had the highest degree of cancer stem cell concentration, highest level of immune cell infiltration, and highest sensitivity not only to predicted anti-PD-1 immunosuppressive therapy but also to conventional chemotherapeutic agents such as cisplatin, sunitinib, and vinblastine; however, this group had the worst prognosis. Comparison of gene set enrichment analysis results for pathway enrichment of various subtypes reveals that the SCE_H subtype activates the important pathways regulating cancer occurrence, development, and even poor prognosis, including epithelial-mesenchymal transition, hypoxia, angiogenesis, KRAS signal upregulation, interleukin 6-mediated JAK-STAT signaling pathway, and inflammatory response. Two identified pairs of transcription factors, GRHL2 and GATA6 and IRF5 and GATA3, possibly have opposite regulatory effects on SCE_H and SCE_L, respectively. The identification of BLCA subtypes based on cancer stem cell gene sets revealed the complex mechanism of carcinogenesis of BLCA and provides a new direction for the diagnosis and treatment of BLCA. | Authentic |
Text : Mutations in RAS or BRAF are associated with poor prognosis and resistance to epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancer (CRC). Despite their common ability to activate downstream genes such as MEK and ERK, the therapeutic benefit of MEK inhibitors for patients with RAS/BRAF mutant CRC is limited, highlighting the need for biomarkers to predict the efficacy of MEK inhibition. Previously, we reported that a change in phosphorylation of ribosomal protein S6 (pS6) after MEK inhibition was significantly associated with sensitivity to MEK inhibition in gastric cancer cells. Here, we investigated the value of the response in pS6 for predicting the efficacy of trametinib, a MEK inhibitor, in patients with RAS/BRAF mutant CRC using patient-derived CRC organoids. We found that a subset of CRC cell lines and organoids were sensitive to trametinib. The change in phosphorylated ERK, a downstream molecule of the RAS/RAF/MEK pathway, was not significantly associated with trametinib sensitivity. On the other hand, only those with sensitivity showed a reduction of pS6 levels in response to trametinib. The change in pS6 after trametinib treatment was detectable by Western blotting, immunohistochemistry or immunocytochemistry. We also demonstrated an impact of MEK inhibition on pS6 in vivo using a xenograft model. Our data suggest that, in combination with patient-derived organoids, immunostaining-based detection of pS6 could be useful for prediction of trametinib sensitivity. | Authentic |
Text : The TNM (Tumor, Node, Metastasis) classification of Union for International Cancer Control is a system describing the anatomical extent of the solid tumors that leads to staging and decision on the type of treatment. The latter TNM system (2017) as compared to the previous version (2010) has brought numerous changes. Our aim was to examine whether significant changes in the new TNM edition have altered the components of the TNM classification in patients and the stage of the disease to which they are ascribed. The study is retrospective and is based on radiological examination reports and case reports of 100 patients of the Department of Pneumonology, Allergology and Oncology of the Medical University in Lublin, Poland. One hundred randomly selected patients, who were hospitalized at the Clinic between 2013 and 2018 with primary lung cancer were enrolled in the study. The chi-square test, Mann-Whitney U test, Kruskal-Wallis test and an appropriate post-hoc test were used in statistical analysis. It was calculated that the T descriptor evaluated as per TNM in revision 8th in comparison to revision 7th changed in 41% of patients, the M descriptor - in 29% of patients, which resulted in change in staging in 11 patients. In spite of this scale amendments, only three patients could be treated differently because of the change in the stage of the disease. Changing the treatment method, including withdrawal from surgery, can help avoid unnecessary treatment, but on the other hand, may potentially reduce the patient's chances of survival by depriving them of the possibility of radical treatment. | Authentic |
Text : The unsatisfactory cure rate of relapsing ALK-positive Anaplastic Large-Cell Lymphoma (ALCL) of childhood calls for the identification of new prognostic markers. Here, the small RNA landscape of pediatric ALK-positive ALCL was defined by RNA sequencing. Overall, 121 miRNAs were significantly dysregulated in ALCL compared to non-neoplastic lymph nodes. The most up-regulated miRNA was miR-21-5p, whereas miR-19a-3p and miR-214-5p were reduced in ALCL. Characterization of miRNA expression in cases that relapsed after first line therapy disclosed a significant association between miR-214-5p down-regulation and aggressive non-common histology. Our results suggest that miR-214-5p level may help to refine the prognostic stratification of pediatric ALK-positive ALCL. | Authentic |
Text : The aim of this study was to elucidate the biological function of long non-coding RNA (lncRNA) HOTTIP (HOXA transcript at the distal tip) in the development of acute myeloid leukemia (AML), and to investigate the potential mechanism. Relative expression levels of HOTTIP, microRNA-608 and DDA1 in AML patients were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Meanwhile, the expressions of these genes in AML cell lines were detected as well. The regulatory effects of HOTTIP, microRNA-608 and DDA1 on the proliferative ability and cell cycle progression of AML cells were examined by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Dual-luciferase reporter gene assay was performed to confirm the binding condition of microRNA-608 to HOTTIP and DDA1. Finally, the specific role of HOTTIP/microRNA-608/DDA1 axis in the development of AML was verified through a series of rescue experiments. HOTTIP was highly expressed in AML-M5 patients than normal controls. No significant difference in HOTTIP expression was found between patients with other subtypes of AML (M0, M1, M2, M3, M4 and M6) and normal controls. HOTTIP expression was significantly up-regulated in AML cell lines U-937 and THP-1. Up-regulation of HOTTIP remarkably promoted the proliferative potential and cell cycle progression of AML cells. Dual-luciferase reporter gene indicated that HOTTIP could bind to microRNA-608, which was lowly expressed in AML-M5 patients. Overexpression of microRNA-608 significantly inhibited the proliferative ability and cell cycle progression of U-937 and THP-1 cells. More importantly, microRNA-608 could partially reverse the regulatory effect of HOTTIP on AML cells. Meanwhile, DDA1 was verified as the target of microRNA-608. Subsequent experiments elucidated that DDA1 significantly accelerated the proliferation and cell cycle of AML cells. Furthermore, DDA1 could reverse the inhibitory effect of microRNA-608 on proliferative ability and cell cycle progression of AML cells. HOTTIP accelerated the proliferative ability and cell cycle of AML cells via up-regulating DDA1 expression by sponging microRNA-608. | Authentic |
Text : Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in gastric cancer and that PRRX1 upregulation is closely correlated with gastric cancer metastasis. In addition, circulating tumor cells (CTCs) play an important role in the process of gastric cancer's distant metastasis. Our study aimed to correlate Prrx1, CTCs and the clinicopathological parameters in primary gastric cancer patients. Expressions of PRRX1 in a sample of 95 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Then the integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SET-imFISH) platform were applied to detect and characterize CTCs in patients with gastric cancer. Finally, their correlations with clinicopathological parameters could be analyzed. The positive rate of PRRX1in gastric cancer was 56.84% and the rate was 36.84% in adjacent normal gastric mucosa, which was confirmed to be statistically significant. In the meantime, both the expression of PRRX1 and the positive rate of CTCs did not significantly correlate with age, gender or histologic type (p>0.05) but significantly related to tumor size, grade of differentiation, lymph node invasion, vascular invasion, metastasis status, depth of tumor invasion, lymph node metastasis and TNM stage (p<0.05). Besides, there was a close relationship between the PRRX1 of gastric cancer and the CTCs of peripheral blood specimens of cancer patients with the correlation coefficient 0.322. Gastric cancer tissues showed that the level of PRRX1 expression was higher compared to the adjacent normal gastric mucosa. Both the expression of PRRX1 and the positive rate of CTCs significantly correlated with clinicopathological parameters. In addition, there was a positive correlation relationship between the PRRX1 of gastric cancer and the CTCs of peripheral blood specimens of cancer patients. These findings demonstrate that higher-level expression of PRRX1 in gastric cancer tissues increased the amount of CTCs in peripheral blood and facilitated the invasion and metastasis in patients with gastric cancer. Meanwhile, it gave some clues to clinical treatment. CTCs may contribute to promotion in diagnosis, therapy monitoring and prognosis of gastric cancer. | Authentic |
Text : The present study examined the effect of microRNA (miRNA/miR)-186-3p and its target gene, minichromosome maintenance complex component 2 (MCM2), on cervical cancer. Cervical cancer tissues and corresponding normal tissues were collected from 48 patients and bioinformatics analysis was performed to identify the differentially expressed genes in cervical cancer. TargetScan and TarBase were used to identify miRNAs, and reverse transcription-quantitative PCR was conducted to detect and evaluate mRNA expression levels. Additionally, MTT and 5-bromo-2-deoxyuridine assays were performed to examine cell proliferation. Cell adhesion, cell cycle distribution and apoptosis were assessed using cell adhesion, flow cytometry and caspase-3/7 activity assays, respectively. The results revealed that miR-186-3p expression was downregulated in cervical cancer tissues and cells, and it negatively regulated MCM2 expression by directly targeting its 3' untranslated region in cervical cancer. Furthermore, MCM2 facilitated cell proliferation and inhibited cell apoptosis, which were reversed by upregulation of miR-186-3p expression. Collectively, the present study suggested that MCM2 and its negative regulator, miR-186-3p, regulate cervical cancer progression. | Authentic |
Text : Lung cancer is an significant cause of death worldwide, and non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. MicroRNAs (miRNAs) have been identified to play key roles in NSCLC development. Recently, it has been reported that miR-605-5p is a cancer-related miRNA in several types of tumors. In this study, we study the role of miR-605-5p in NSCLC cells. We find that miR-605-5p is upregulated in NSCLC cells. Overexpression of miR-605-5p significantly promotes lung cancer invasion and migration in H460 and H1299 cells. Besides this, miR-605-5p also promotes lung cancer cell carcinoma proliferation and metastasis in vivo. However, downregulation of miR-605-5p inhibits cell invasion and migration by inhibiting lung cancer cell carcinoma proliferation and metastasis. In addition, the luciferase report assay identifies 3'-untranslated region tumor necrosis factor α-induced protein 3 (TNFAIP3) as a target of miR-605-5p. Silencing of TNFAIP3 promotes invasion and proliferation in lung cancer. In addition, the knockdown of TNFAIP3 restores the significant decrease in invasion and proliferation in miR-605-5p-inhibitor-transfected lung cancer cells. In conclusion, miR-605-5p promotes invasion and proliferation by targeting TNFAIP3 in NSCLC, and may provide possible biomarkers for NSCLC therapy. | Authentic |
Text : Many alternative and complementary therapies for cancer have been reported. The objective of the present work is to examine antitumor and immune-modulatory properties of dual-treatment based on levamisole (Lms) and/or taurine (Tau) in Ehrlich ascites carcinoma-bearing mice. In the current study, Lms (10 mg/kg; subcutaneously) and Tau (640 mg/kg; intragastrically) was administered alone or as a dual-treatment. Lms or Tau was administered in combination with cyclophosphamide (CTX) (100 mg/kg; intraperitoneal) in mice bearing Ehrlich ascites carcinoma. Treatment with CTX or (Lms plus Tau) significantly reduced the ascitic tumor cell count, percentage of tumor cell viability while elevated the tumor inhibition rate and apoptosis percentage compared to non-treated animals. Dual-treatment (Lms and CTX) or (Tau and CTX) significantly potentiated the reduction of the ascitic tumor cell count, viability and augmented the tumor inhibition rate and apoptosis percentage compared to CTX-treated mice. Dual-treatment of (Lms plus Tau), (Lms plus CTX) or (Tau plus CTX) altered splenocytes immunological profile of CD3+CD4+, CD3+CD8+, CD4+CD25+ and CD11b+Ly6G+ cells in order to achieve better immune surveillance against tumor cells. In conclusion, dual-treatments based on Lms and/or Tau are promising therapies for cancer, not only due to its abilities to induce apoptosis in the tumor cells and modulate the immune response against them, but also due to its capabilities to potentiate the chemotherapy anticancer efficacy and minimize its adverse effects. | Authentic |
Text : Recent studies have revealed that long non-coding RNAs (lncRNAs) have a crucial role in tumor progression. Renal cell cancer (RCC) is a common type of fatal gynecological cancer worldwide. This study aims to identify the role of lncRNA Small nucleolar RNA host gene 7 (SNHG7) in the progression of RCC. Expression of lncRNA SNHG7 in both RCC cells and 50 pairs of tissue samples was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the function of SNHG7 was identified by performing cell apoptosis assay, colony formation assay and proliferation assay in vitro. The underlying mechanism assays including RT-qPCR and Western blot assay were conducted. SNHG7 expression was remarkably upregulated in tumor tissues when compared with adjacent tissues. Moreover, RCC cell proliferation was inhibited and cell apoptosis was promoted after knockdown of SNHG7 in vitro. Moreover, after knockdown of SNHG7, CDKN1A was upregulated at mRNA and protein level in vitro. Furthermore, the expression of CDKN1A in tumor tissues was negatively correlated to the expression of SNHG7. These results above suggest that SNHG7 could promote cell proliferation and inhibit cell apoptosis in RCC through downregulating CDKN1A, which may offer a new therapeutic intervention for RCC patients. | Authentic |
Text : Long non-coding RNA DLX6 antisense RNA 1 (DLX6-AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6-AS1, microRNA (miR)-193b-3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6-AS1/miR-193b-3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6-AS1, miR-193b-3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6-AS1/miR-193b-3p-related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6-AS1 and HOXA1 were up-regulated, and miR-193b-3p was down-regulated in TC. Depleted DLX6-AS1 or restored miR-193b-3p disturbed cell growth and promoted autophagy. DLX6-AS1 targeted miR-193b-3p and positively regulated HOXA1. miR-193b-3p inhibition mitigated the impaired tumorigenesis induced by down-regulated DLX6-AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6-AS1 depletion hinders TC cell growth and promotes autophagy via up-regulating miR-193b-3p and down-regulating HOXA1. | Authentic |
Text : Our study is to examine the citron rho-interacting, serine/threonine kinase 21 (CIT) in bladder cancer. We examined CIT level in human bladder cancer tissues by immunohistochemical staining. To explore the impact of CIT on cell proliferation and apoptosis, we down-regulated its expression in two human bladder cancer cell lines, 5367 and T24. We examined cell growth in 5367 and T24. We also performed in vivo analysis using T24 cells. We further used microarray expression profiling to investigate genes differentially expressed in T24 cells with CIT down-regulated. In 100 human samples, CIT was expressed by only 2 of 30 (6.7 %) controls in bladder tissues, whereas by 64 of 70 (91.4 %) cancer patients in tumor tissues (p < 0.001). in vitro analysis demonstrated that CIT knockdown represses cell proliferation by 50 % in both cells and colony formation (77 ± 5 vs. 13 ± 2, p = 0.001 for T24, 58 ± 3 vs. 1 ± 1, p < 0.001 for 5637). We also found CIT knockdown could induce cell cycle arrest, and promote apoptosis in both cells. Tumor-volume monitoring and live in vivo bladder cancer imaging in human xenograft model confirmed that CIT knockdown reduces tumor volume (668.4 ± 333.0 vs. 305.7 ± 170.4 mm3, p = 0.02) and weight (0.27 ± 0.15 vs. 0.57 ± 0.32 g, p = 0.02). Microarray analysis revealed that CIT may regulate cell cycle signalling pathway through various cell cycle regulators. In summary, we provided clinical and experimental evidence that CIT may promote bladder cancer through regulation of cell cycle pathway. | Authentic |
Text : A high Treg/CD8 T cell ratio in ovarian carcinoma was negatively associated with the prognosis of the patients. The human follicular regulatory T (Tfr) cells are a newly characterized subset of Treg cells with features of both follicular helper T (Tfh) cells (CXCR5+) and canonical Treg cells (CD25+Foxp3+). The role of Tfr cells in ovarian cancer is yet unclear. We found that in peripheral blood, the ovarian cancer patients presented significantly higher levels of both CD4+CD25+CD127-CXCR5+ T cells and CD4+CD25+CD127-CXCR5+Foxp3+ T cells than the healthy controls. In resected tumor samples, Tfr cells represented a much greater percentage of lymphocytes than in peripheral blood. Interestingly, the circulating Tfr cells from ovarian cancer patients presented significantly higher TGFB1 and IL10 expression than their counterparts in healthy controls directly ex vivo, and significantly higher IL10 after stimulation. The tumor-infiltrating Tfr cells presented further upregulated expression of TGFB1 and IL10. In addition, the levels of TGFB1 and IL10 expression by Tfr cells negatively associated with the expression of IFNG in tumor-infiltrating CD8 T cells. In an in vitro CD8 T cell/Tfr cell coculture system, we found that Tfr cells could significantly suppress the activation of CD8 T cells, in a manner that was dependent on IL-10 and probably on TGF-β. Overall, our study found that Tfr cells could suppress CD8 T cells, and in ovarian cancer patients, the Tfr cells were increased in both frequency and function. | Authentic |
Text : To analyze the impact of the reversal penetrating technique (RPT) for intrathoracic gastroesophageal mechanical anastomosis on the development of anastomotic complications in Ivor Lewis minimally invasive esophagectomy (ILMIE), and to further identify the risk factors for the development of anastomotic leakage and stricture. A retrospective observational study was conducted using the clinical data of 316 patients with esophageal carcinoma (EC) who underwent ILMIE from January 2012 to December 2019. The participants were divided into three groups, namely the RPT group, the transoral Orvil technique (TOT) group, and the purse-string technique (PST) group, according to the different stapler placement methods for intrathoracic mechanistic circular stapling. Multivariate analysis was performed to investigate the association of risk factors with anastomotic leakage and stricture. There were 154 patients in the RPT group, 78 in the TOT group, and 84 in the PST group for intrathoracic gastroesophageal circular stapling in ILMIE. There were no differences in intraoperative anastomosis-related conditions including conversion of open operations, and lymph nodes harvested between the three groups. However, the mean total operative time and gastroesophageal anastomosis time in the RPT group were significantly shorter than those in the other groups (both P<0.05). The rates of anastomotic leakage and stricture showed no statistical differences between the three groups (leakage: P=0.875; stricture: P=0.942). Multivariate analysis revealed that the RPT method of anvil placement did not increase the probability of anastomotic leakage [RPT: reference; TOT: odds ratio (OR) 0.422, P=0.341; PST: OR 1.436, P=0.645] and stricture (RPT: reference; TOT: OR 0.579, P=0.376; PST: OR 1.195, P=0.755). The RPT method of anvil placement for intrathoracic gastroesophageal circular stapling does not increase the risk of anastomotic complications in ILMIE, but had significantly shorter surgical time and anastomosis time. | Authentic |
Text : Gastric cancer (GC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Accumulating evidence reported that microRNA (miR)-133a was involved in GC. This study aimed to investigate the function and mechanism of miR-133a in the development and progression of GC. The expression of miR-133a and presenilin 1 (PSEN1) in two GC cell lines, SGC-7901 and BGC-823, were inhibited and overexpressed by transient transfections. Thereafter, cell viability, migration, and apoptosis were measured by trypan blue exclusion assay, transwell migration assay, and flow cytometry assay, respectively. Dual-luciferase reporter assay was conducted to verify whether PSEN1 was a direct target of miR-133a. Furthermore, quantitative real-time polymerase chain reaction and Western blot analysis were mainly performed to assess the expression changes of epithelial-mesenchymal transition (EMT)-associated proteins, apoptosis-related proteins, and Notch pathway proteins. MiR-133a inhibitor significantly increased cell viability and migration, while miR-133a mimic decreased cell viability, migration, and induced apoptosis. miR-133a suppression accelerated transforming growth factor-β1 (TGF-β1)-induce EMT, as evidenced by upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Slug. Of contrast, miR-133a overexpression blocked TGF-β1-induce EMT by altering these factors. PSEN1 was a direct target of miR-133a, and suppression of PSEN1 abolished the promoting functions of miR-133 suppression on cell growth and metastasis. Moreover, PSEN1 inhibition decreased Notch 1, Notch 2, and Notch 3 protein expressions. This study demonstrates an antigrowth and antimetastasis role of miR-133a in GC cells. Additionally, miR-133a acts as a tumor suppressor may be via targeting PSEN1. | Counterfeit |
Text : Ovarian cancer remains the leading cause of death among all gynaecological cancers, illustrating the urgent need to understand the molecular mechanisms involved in this disease. Eukaryotic initiation factor 3c (EIF3c) plays an important role in protein translation and cancer cell growth and proliferation, but its role in human ovarian cancer is unclear. Our results showed that EIF3c silencing significantly up-regulated 217 and down-regulated 340 genes. Ingenuity Pathway Analysis (IPA) indicated that the top differentially expressed genes are involved in 'Classical Pathways', 'Diseases and Functions' and 'Networks', especially those involved in signalling and cellular growth and proliferation. In addition, eIF3c silencing inhibited cellular proliferation, enhanced apoptosis and regulated the expression of apoptosis-associated proteins. In conclusion, these results indicate that by dysregulating translational initiation, eIF3c plays an important role in the proliferation and survival of human ovarian cancer cells. These results should provide experimental directions for further in-depth studies on important human ovarian cancer cell pathways. | Authentic |
Text : The comprehensive pathological peculiarities of Neferine (NEF) have been testified in disparate diseases. But, the functions of NEF in choriocarcinoma progression remain unexplored. The research endeavoured to uncover the anti-tumour action of NEF in choriocarcinoma cells. NEF at diverse doses was employed to dispose JEG-3 and HTR-8 cells, and cell viability assessment adopted CCK-8 assay. After 60 μg/mL NEF management, BrdU-positive cells, apoptosis, migration, invasion and correlative factors were assessed. CHRF expression in choriocarcinoma tumour and choriocarcinoma cell lines was estimated via RT-qPCR. Then, the functions of overexpressed CHRF in NEF-disposed cells were determined. At last, impacts of NEF on PI3K/AKT/mTOR and ERK1/2 pathways were evaluated. Results showed that NEF restrained cell proliferation, triggered apoptosis and repressed migration and invasion in JEG-3 and HTR-8 cells. CHRF was ascended in choriocarcinoma tissues and NEF repressed CHRF expression in choriocarcinoma cell lines. Additionally, overexpressed CHRF abolished the above functions of NEF in choriocarcinoma cells proliferation, apoptosis, migration and invasion. Further, NEF impeded PI3K/AKT/mTOR and ERK1/2 pathways via repressing CHRF. The explorations testified that NEF exhibited the anti-tumour action in JEG-3 and HTR-8 cells via hindering PI3K/AKT/mTOR and ERK1/2 pathways by mediating CHRF. | Authentic |
Text : The aim of this study was to investigate in vitro magnetic resonance imaging (MRI) of PDAC using ENO1-targeted superparamagnetic iron oxide nanoparticles and xenograft models. Expression level and location of ENO1 protein in pancreatic cancer cell lines of CFPAC-1 and MiaPaCa-2 were detected by Western blotting, flow cytometry and confocal microscopy. Dex-g-PCL/SPIO nanoparticles targeting ENO1 were constructed with ENO1 antibody and characterized by MRI. In addition, ENO1-Dex-g-PCL/SPIO nanoparticles were tested to assess their efficacy on the detection of PDAC using in vitro and in vivo MRI. The results showed that ENO1 was expressed in both human PDAC cell lines of CFPAC-1 and MiaPaCa-2, demonstrating that the localization of cytoplasm and membrane was dominant. It was confirmed that ENO1 antibody was connected to the SPIO surface in ENO1-Dex-g-PCL/SPIO nanoparticles. The nanoparticles had satisfactory superparamagnetism and significantly enhance the detection of PDAC by in vivo and in vitro MRI. In conclusion, ENO1 can serve as a membrane protein expressed on human PDAC cell lines. ENO1-targeted SPIO nanoparticles using ENO1 antibody can increase the efficiency of detection of PDAC by in vitro and in vivo MRI. | Authentic |
Text : Lung cancer is the leading cause of cancer-related death in many countries, and an accurate histopathological diagnosis is of great importance in subsequent treatment. The aim of this study was to establish the random forest (RF) model based on radiomic features to automatically classify and predict lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), and small cell lung cancer (SCLC) on unenhanced computed tomography (CT) images. Eight hundred and fifty-two patients (mean age: 61.4, range: 29-87, male/female: 536/316) with preoperative unenhanced CT and postoperative histopathologically confirmed primary lung cancers, including 525 patients with ADC, 161 patients with SCC, and 166 patients with SCLC, were included in this retrospective study. Radiomic features were extracted, selected, and then used to establish the RF classification model to analyse and classify primary lung cancers into three subtypes, including ADC, SCC, and SCLC according to histopathological results. The training (446 ADC, 137 SCC, and 141 SCLC) and testing cohorts (79 ADC, 24 SCC, and 25 SCLC) accounted for 85% and 15% of the whole datasets, respectively. The prediction performance of the RF classification model was evaluated by F1 scores and the receiver operating characteristic (ROC) curve. On the testing cohort, the areas under the ROC curve (AUC) of the RF model in classifying ADC, SCC, and SCLC were 0.74, 0.77, and 0.88, respectively. The F1 scores achieved 0.80, 0.40, and 0.73 in ADC, SCC, and SCLC, respectively, and the weighted average F1 score was 0.71. In addition, for the RF classification model, the precisions were 0.72, 0.64, and 0.70; the recalls were 0.86, 0.29, and 0.76; and the specificities were 0.55, 0.96, and 0.92 in ADC, SCC, and SCLC. The primary lung cancers were feasibly and effectively classified into ADC, SCC, and SCLC based on the combination of RF classification model and radiomic features, which has the potential for noninvasive predicting histological subtypes of primary lung cancers. | Authentic |
Text : Cancer stem cells (CSCs), which are involved in cancer initiation and metastasis, could potentially release exosomes that mediate cellular communication by delivering microRNAs (miRNAs). Based on the role of miR-26a in angiogenesis of glioma, our study was performed to investigate whether glioma stem cells (GSCs)-derived exosomes containing miR-26a could exert effects on angiogenesis of microvessel endothelial cells in glioma, in order to provide a new therapeutic RNA vehicle for glioma therapies. The expression of miR-26a and PTEN in glioma was quantified and the interaction among miR-26a, PTEN and PI3K/Akt signaling pathway was examined. Next, a series of gain- and loss-of function experiments were conducted to determine the role of miR-26a in angiogenesis of human brain microvascular endothelial cells (HBMECs). Subsequently, HBMECs were exposed to exosomes derived from GSCs with the gain-/loss-of-function of miR-26a. Finally, the effect of exosomal miR-26a on angiogenesis of HBMECs was assessed both in vitro and in vivo. The results revealed that PTEN was down-regulated, while miR-26a was up-regulated in glioma. miR-26a activated the PI3K/Akt signaling pathway by targeting PTEN. Restored miR-26a promoted proliferation, migration, tube formation, and angiogenesis of HBMECs in vitro. In addition, GSCs-derived exosomes overexpressing miR-26a contributed to enhanced proliferation and angiogenesis of HBMECs in vitro through inhibition of PTEN. The angiogenic effects of GSCs-derived exosomes overexpressing miR-26a in vivo were consistent with the above-mentioned in vitro findings. Collectively, our study demonstrates that GSCs-derived exosomal miR-26a promotes angiogenesis of HBMECs, highlighting an angiogenic role of miR-26a via exosomes. | Counterfeit |
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 : Osteoarthritis is the most frequent chronic bone and joint diseases in older populations all over the world. Lipopolysaccharide (LPS)-induced murine chondrogenic ATDC5 cell model has been widely used for testing new osteoarthritis therapeutic targets. This study aimed to explore the effects of microRNA-136 (miR-136) on LPS-induced ATDC5 cell injury and inflammatory cytokine expression, as well as underlying potential mechanism. We found that LPS remarkably inhibited ATDC5 cell viability, induced ATDC5 cell apoptosis, and upregulated the expression of inflammatory cytokines, including interleukin 1β (IL-1β), IL-6, IL-8, and tumor necrosis factor α (TNF-α; P < .01 or < .001). Moreover, LPS obviously upregulated the expression of miR-136 in ATDC5 cells (P < .05). Overexpression of miR-136 markedly exacerbated the LPS-induced ATDC5 cell viability inhibition, cell apoptosis enhancement, and inflammatory cytokine expression (P < .05), and suppression of miR-136 had opposite effects (P < .05). Myeloid cell leukemia 1 (Mcl-1) was a direct target gene of miR-136, which participated in the effect of miR-136 on LPS-induced ATDC5 cell inflammatory injury. Overexpression of Mcl-1 alleviated the LPS-induced inactivation of Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways, while suppression of Mcl-1 had opposite effects. To conclude, this study verified that miR-136 promoted LPS-induced ATDC5 cell injury and inflammatory cytokine expression by targeting Mcl-1, and Mcl-1 was involved in the regulatory effects of LPS on Wnt/β-catenin and JAK/STAT signaling pathways in ATDC5 cells. | Counterfeit |
Text : Epithelial-to-mesenchymal transition (EMT) in cancer cells could convert epithelial-like cells to mesenchymal-like cells, resulting in the increased capacity of migration and invasion of cancer cells, and is an essential step in triple negative breast cancer (TNBC) development. Recent reports exert that these EMT-activated TNBC cells are more resistant to immune attacks, with high levels of programmed death ligand1 (PD-L1). Hence, it is worthwhile to find an effective approach in inhibiting EMT-activated TNBC cells. (-)-Sativan (SA) is a naturally isolated isoflavane and could be isolated from Spatholobus suberectus, a common traditional Chinese medicine used for breast cancer treatment. It was the first time that SA exerted anti-cancer effects on breast cancer cells, according to our study. In this study, SA displayed a significant inhibitory effect on the proliferation of TNBC cells by inducing apoptosis. SA increased Bax expression, and decreased Bcl-2 protein levels. SA inhibited cell migration and invasion of MDA-MB-231 and BT-549 cells. SA could decrease N-cadherin, Snail, Vimentin, and PD-L1 expression. SA increased miR-200c expression, and decreased PD-L1 expression. Luciferase assay showed that miR-200c directly targeted PD-L1. SA promoted tumor cell susceptibility to CTL-mediated lysis. Further study confirmed that SA could inhibit PD-L1 expression and EMT by up-regulating miR-200c. In vivo results displayed that SA could also inhibit tumor volumes and weights. These findings indicate that SA exerts an inhibitory effect on TNBC cell proliferation, migration, invasion, and tumor gtrowth, and partly provide evidence for the anti-breast cancer effect of Spatholobus suberectus Dunn in TNBC therapy. | Authentic |
Text : Krüppel-like factor 4 (KLF4) is an important transcription factor that is expressed in a variety of tissues and regulates many critical physiologic and cellular processes, including cell proliferation, differentiation, stem cell reprogramming, maintenance of genomic stability, and normal tissue homeostasis. KLF4 has both tumor suppressive and oncogenic functions in gastrointestinal and other cancers. These functions are thought to be context dependent, but how KLF4 exerts these differential functions and the molecular mechanisms behind them remain poorly understood. Recent studies have shown that the KLF4 gene undergoes alternative splicing, and the protein products of certain transcripts antagonize wild-type KLF4 function, suggesting an additional layer of regulation of KLF4 function. Therefore, detailed study of KLF4 alternative splicing may not only provide new insights into the complexity of KLF4 functions but also lead to rational targeting of KLF4 for cancer prevention and therapy. | Authentic |
Text : Thyroid hormone receptor interactor 13 (TRIP13) has been reported to be overexpressed in serval types of human cancers, and regulate tumor cell proliferation, migration and invasion. However, the role of TRIP13 in prostate cancer was still unclear. In our study, the correlation between TRIP13 expression and clinical parameters including prognosis was evaluated in 160 prostate cancer patients. Moreover, the MTT assay, cell migration and invasion assays were performed to assess the effect of TRIP13 on prostate cancer cell biological behaviour. In our results, the expression status of TRIP13 was observed to be elevated in prostate cancer tissue samples through analyzing microarray (GSE55945). Furthermore, mRNA and protein TRIP13 expression were confirmed to be overexpressed in prostate cancer tissue samples and cell lines. High-expression of TRIP13 was correlated with present lymph node involvement, distant metastasis, high Gleason score, levels of serum PSA and poor prognosis in prostate cancer patients. The gain-of-function and loss-of-function studies suggested that TRIP13 functioned as oncogene to regulate prostate cancer cell proliferation, migration, invasion through controlling YWHAZ and epithelial-mesenchymal transition (EMT)-associated genes. In conclusion, TRIP13 is correlated with clinical progression and poor prognosis, and serves as oncogene in prostate cancer. | Authentic |
Text : Acne rosacea is a type of chronic dermatosis with the characteristics of erubescence, angiotelectasis and pustule formation. However, current treatment methods are limited due to the side effects. Artesunate demonstrated a promising therapeutic efficacy with a high safety margin. HaCaT cells were treated with antibacterial peptide LL‑37 to simulate rosacea caused by Demodex folliculorum (D. folliculorum) infection. Cell Counting kit 8 and flow cytometry assays were performed to measure cellular proliferation, apoptosis, the stage of the cell cycle and reactive oxygen species generation in order to determine the level of cell damage. Then the damaged cells were treated with different concentrations of artesunate and doxycycline to determine the therapeutic effect of artesunate. Pro‑inflammatory cytokines tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6, IL‑8 and C‑C motif chemokine 2 (MCP‑1) were measured using an ELISA, while western blotting was used to detect the expression of Janus kinase 2 (JAK2) and signal transducer and transcription activator (STAT3). As a result, LL‑37 treated HaCaT cells decreased in cell viability, had an increased apoptotic rate and cell cycle arrest, indicating that cell damage caused by rosacea was simulated. In addition, upregulated concentrations of the pro‑inflammatory cytokines TNF‑α, IL‑6, IL‑8 and MCP‑1 were attenuated in the artesunate group in a dose‑dependent fashion, indicating the therapeutic effect of artesunate. Furthermore, higher concentrations of artesunate exhibited an improved effect compared with the doxycycline group. In addition, increased expression levels of JAK2 and STAT3 following treatment with LL‑37 suggested that rosacea caused by D. folliculorum infection may lead to inflammation through the JAK/STAT signaling pathway. In conclusion, the potential mechanism by which damage occurs in rosacea was revealed and a promising therapeutic method against rosacea was demonstrated. | Counterfeit |
Text : Hindrance to successful therapy of colon cancer is generally characterized with reduced potency of a single drug at the active site of cancer, poor drug release, and most importantly, potential toxic side effects of the drug resulting in cytotoxicity. Therefore, we investigated combinatorial drug micelles which are a potent combination of twin anticancer drugs (indomethacin and piroxicam, IND+PIR mc) for successful therapeutics of colon cancer. The novel combinatorial micelles showed improved drug encapsulation efficiency, an in vitro burst release of the dual drugs, increased cytocompatibility and increased efficacy in tumor reduction (weight and volume) than in single drug micelles (IND mc or PIR mc). The improved IND+PIR MC were to have small size 150.36 ± 15.13 nm (to avoid being taken up by liver, lungs or kidney or to sediment) with poly dispersity index (PDI) value at 0.24 ± 0.01. The PDI values suggest homogenous distribution. Encapsulation efficiency of IND+PIR mc was calculated at 86%. IND+PR mc had improved biocompatibility as demonstrated by CRL-1459™ (normal colon) cell line than IND mc or PIR mc individually. The in vivo studies in mice model clearly depict that subcutaneous tumor weight reduced by almost 75% and volume reduced drastically by 55% on administration of IND+PIR mc than IND mc or PIR mc. Furthermore, fewer side effects were found with IND+PIR mc. To conclude, IND+PIR mc may be a potential anticancer strategy to be explored more in the future. | Authentic |
Text : The use of chromosomal microarray analysis (CMA) in prenatal diagnosis of chromosomal and genetic diseases has resulted in a significant improvement in the diagnosis of genetically caused congenital malformations, neurodevelopmental disorders, and congenital anomalies, with a high diagnostic yield in selected prenatal cases. The objective of this study was to evaluate the application of CMA in the prenatal diagnosis of high-risk pregnant women. A total of 576 pregnancies were selected from May 2018 to October 2020 in our hospital, including amniotic fluid chromosome, karyotype analysis, and CMA detection. The study group was divided into two groups based on the indications for testing: group A has 88 patients at the age of 35 years or older, and group B patients were in high-risk pregnancies, which consisted of 33 cases of bad pregnancy history, 252 high-risk serological screenings, 70 high-risk non-invasive prenatal testing (NIPT), 65 cases of B-ultrasound indicated fetal development abnormalities or ultrasonic soft marker abnormalities, and 68 other cases of pregnant women or both who have genetic or chromosomal abnormalities. At last, we have an analysis of the detection rate from different testing methods. Based on the follow-up test, 576 high-risk pregnant women showed an amniotic fluid chromosome karyotype rate of 18.1% (104/576), and the remaining 472 of these cases suffered a CNV ratio of 14.2% (67/472). 472 women of low clinical relevance are at 4.87% (23/472), 16 people showed a clear cause ratio = 3.39% (16/472), and 28 of the 472 (5.93%) cases showed polymorphism. In our study, CMA significantly improved the fetal detection rate and diagnosis rate in high-risk pregnant women, which proved to be a very useful method in the diagnosis of genetically caused neurodevelopmental disorders and congenital anomalies. The use of CMA in high-risk pregnant women is justified, and these women can detect an additional (3.40%, 16/472) of pathogenic microdeletions and microduplications in the cases. | Counterfeit |
Text : Capecitabine (CAP) is an FDA-approved and frequently used chemotherapeutic agent for the treatment of various cancers. However, there are some side effects and chemoresistance limiting its use. Nanotechnological approaches can enhance the efficacy of anticancer drugs. In this study, CAP-loaded nanoniosomes were prepared. Nanoniosomes were prepared by the method of thin film hydration wherein CAP was loaded into the nanoniosomes. Nanoniosomes were then characterized by field emission scanning electron microscopy and (particle) vesicle size analysis. The cytotoxicity effect of the nanoniosomes were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CAP was loaded into the nanoniosomes and loading capacity and entrapment efficiency were determined. The vesicle size of the nanoniosomes was obtained in the nanometer scale, and CAP release profiles from the nanoniosomes were also obtained. Finally, the cytotoxicity effect of CAP and CAP-loaded nanoniosomes were evaluated toward MCF7 and PANC1 cell lines. The nanoniosomes with an amphipathic structure can penetrate into the cells with an enhanced release rate. These caused the toxicity of drug in the nanoniosomes to be higher than the free drug. | Authentic |
Text : Asymmetric division (ASD), the unique characteristic of normal stem cells, is regarded as a stemness marker when applied to the study of cancer stem cells (CSCs). However, the role of ASD in the self-renewal of CSCs and its regulation remain largely unknown. Here, we first established a mouse Lewis lung carcinoma CSC cell line that could undergo asymmetric division (LLC-ASD cells) derived from the parental mouse Lewis lung carcinoma cancer cells (LLC-Parental cells). In vitro assessment of stemness by RT-qPCR and western blot analysis of stem cell markers, clonogenic assay (p < 0.001), single cell spheroid formation assay (p < 0.05) and 96-well-plate single-cell cloning assay (p < 0.01) indicated that the LLC-ASD cells exhibited stronger stemness features in comparison to the LLC-Parental cells. In vivo, tumorigenicity of LLC-ASD cells, transplanted subcutaneously to the nude mice, was increased compared to that of LLC-parental cells (p < 0.05). Further, Neuralized1a, a regulator of ASD in normal stem cells, was highly expressed in the LLC-ASD cells. Silencing Neuralized1a expression in LLC-ASD cells by siRNA weakened the stemness features measured by the in vitro assays listed above (p < 0.05). The tumorigenic ability was also decreased in the nude mice upon Neuralized1a silencing (p < 0.05). Collectively, the present study suggests that Neuralized1a regulates the stemness of LLC-ASD cells which could be the new marker and therapeutic target of CSCs. | Authentic |
Text : Lung adenocarcinomas injured greatly on the people worldwide. Although clinic experiments and gene profiling analyses had been well performed, to our knowledge, systemic coexpression analysis of human genes for this cancer is still limited to date. Here, using the published data GSE75037, we built the coexpression modules of genes by Weighted Gene Co-Expression Network Analysis (WGCNA), and investigated function and protein-protein interaction network of coexpression genes by Database for Annotation, visualization, and Integrated Discovery (DAVID) and String database, respectively. First, 11 coexpression modules were conducted for 5,000 genes in the 83 samples recently. Number of genes for each module ranged from 90 to 1,260, with the mean of 454. Second, interaction relationships of hub-genes between pairwise modules showed great differences, suggesting relatively high scale independence of the modules. Third, functional enrichment of the coexpression modules showed great differences. We found that genes in modules 8 significantly enriched in the biological process and/or pathways of cell adhesion, extracellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway, and so forth. It was inferred as the key module underlying lung adenocarcinomas. Furthermore, PPI analysis revealed that the genes COL1A1, COL1A2, COL3A1, CTGF, and BGN owned the largest number of adjacency genes, unveiling that they may functioned importantly during the occurrence of lung adenocarcinomas. To summary, genes involved in cell adhesion, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway play crucial roles in human lung adenocarcinomas. | Authentic |
Text : Lung cancer is a leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) constitutes ~85% of lung cancers. However, the mechanisms underlying the progression of NSCLC remain unclear. In this study, we found the mRNA and protein expression levels of integrin αv are both increased in NSCLC tissues compared to healthy ones, which indicates that integrin αv may play an important role in NSCLC progression. To further investigate the roles of integrin αv in NSCLC, we overexpressed the integrin αv gene in the NSCLC cell line A549, and found that the cell proliferative ability increased. The apoptosis of A549 cells was inhibited with overexpression of integrin αv. To elucidate the molecular mechanism underlying the role of integrin αv in promoting NSCLC progression, we studied the expression of proteins from a number of important pathways associated with tumorigenesis, and found that the extracellular signal regulated protein kinase (ERK)1/2 signaling pathway may be involved in the mediation of the observed integrin αv effects. component of an important pathway for tumorigenesis, the ERK 1/2. Following inhibition of ERK 1/2 signaling, the proliferation of A549 cells induced by integrin αv was reduced, while the inhibition of apoptosis was attenuated. Our findings demonstrate that integrin αv promotes the proliferation of the human lung cancer cell line A549 by activating the ERK 1/2 signaling pathway, which suggests that this pathway may be a promising target for the treatment of human lung cancer. | Authentic |
Text : An elevated circulating level of trimethylamine N-oxide (TMAO) has been identified as a risk factor for numerous diseases, including cardiovascular disease (CVD) and colon cancer. TMAO is formed from trimethylamine (TMA)-precursors such as choline via the combined action of the gut microbiota and liver. We conducted a Mediterranean diet intervention that increased intakes of fiber and changed intakes of many other foods containing fat to increase the relative amount of mono-unsaturated fats in the diet. The Mediterranean diet is associated with reduced risks of chronic diseases and might counteract the pro-inflammatory effects of increased TMAO formation. Therefore, the purpose of this study was to determine if the Mediterranean diet would reduce TMAO concentrations. Fasting TMAO concentrations were measured before and after six-months of dietary intervention in 115 healthy people at increased risk for colon cancer. No significant changes in plasma TMAO or in the ratios of TMAO to precursor compounds were found in either the Mediterranean group or the comparison group that followed a Healthy Eating diet. TMAO concentrations exhibited positive correlations with age and markers of metabolic health. TMAO concentrations were not associated with circulating cytokines, but the relative abundance of Akkermansia mucinophilia in colon biopsies was modestly and inversely correlated with baseline TMAO, choline, and betaine serum concentrations. These results suggest that broad dietary pattern intervention over six months may not be sufficient for reducing TMAO concentrations in an otherwise healthy population. Disruption of the conversion of dietary TMA to TMAO should be the focus of future studies. | Authentic |
Text : Although tumor vaccines have been considered a promising immunotherapy approach, therapeutic tumor vaccines are mostly disappointing in the clinic due to vaccine weak immunogenicity. Cancer stem cells (CSCs) may broaden the antigenic breadth and effectively induce the immune responses against autologous cancer cells. Here we report on the development of the B16F10 CD133+CD44+CSCs (B16F10 CSCs) vaccine to induce tumor immunity to melanoma in mice. Efficacy of against melanoma was evaluated by analysis of tumor growth and mouse survival. Immunogenicity was assessed by ELISA and flow cytometric assays, including serum cytokines, cytotoxic activity of NK cells and splenocytes in the immunized mice. The results showed that the B16F10 CSC vaccine resulted in tumor shrinkage and mouse lifespan extension. The cytotoxic activity and IFN-γ level were significantly increased in mice immunized with B16F10 CSC vaccine compared with the mice immunized with control vaccines. Additionally, New York esophageal squamous cell carcinoma-1, an efficient tumor associated antigen over-expressed by B16F10 CSCs, was markedly reduced in expression in melanoma tissue, suggesting decrease of CSC subpopulation due to B16F10 CSC vaccination. Collectively, the findings may represent a new powerful approach for treatment of melanoma by B16F10 CSC vaccination. | Authentic |
Text : Background: Metastasis is the primary cause of cancer deaths, warranting further investigation. This study assessed microRNA-153 (miR-153) expression in bladder cancer tissues and investigated the underlying molecular mechanism of miR-153-mediated regulation of bladder cancer cells. Methods: Paired tissue specimens from 45 bladder cancer patients were collected for qRT-PCR. The Cancer Genome Atlas (TCGA) dataset was used to identify associations of miR-153 with bladder cancer prognosis. Bladder cancer tissues and immortalized cell lines were used for the following experiments: miR-153 mimics and indoleamine 2,3-dioxygenase 1 (IDO1) siRNA transfection; Western blot, cell viability, colony formation, and Transwell analyses; nude mouse xenograft; and chicken embryo chorioallantoic membrane angiogenesis (CAM) assays. Human umbilical vein endothelial cells (HUVECs) were co-cultured with bladder cancer cells for the tube formation assay. The luciferase reporter assay was used to confirm miR-153-targeting genes. Results: miR-153 expression was downregulated in bladder cancer tissues and cell lines, and reduced miR-153 expression was associated with advanced tumor stage and poor overall survival of patients. Moreover, miR-153 expression inhibited bladder cancer cell growth by promoting tumor cell apoptosis, migration, invasion, and endothelial mesenchymal transition (EMT) in vitro and tumor xenograft growth in vivo, while miR-153 expression suppressed HUVEC and CAM angiogenesis. At the gene level, miR-153 targeted IDO1 expression and inhibited bladder cancer cell tryptophan metabolism through inhibiting IL6/STAT3/VEGF signaling. Conclusions: Collectively, our data demonstrate that miR-153 exerts anti-tumor activity in bladder cancer by targeting IDO1 expression. Future studies will investigate miR-153 as a novel therapeutic target for bladder cancer patients. | Authentic |
Text : Incorporation of endothelial cells or their progenitor cells into newly sprouting blood vessels can contribute to tissue vascularization after ischemic injury. However, the interaction of the stem cells-derived endothelial cells with angiogenesis within tumors is not well understood. The aim of this study was to examine the efficiency of endothelial-like cells derived from MSCs in controlling breast tumor growth associated with abnormal angiogenesis. For this purpose, Balb/c mouse model of breast carcinoma was developed and subjected to intra tumor (I.T)/intra venous (I.V) therapy with undifferentiated MSCs or endothelial cells derived from them. The homing of the stem cells was approved by measuring different markers as well as tracing green fluorescence protein (GFP)-labeled MSCs in the tumors. Tumor growth was measured following cell therapy using a digital caliper. At the end of treatment period (30 days) the angiogenesis markers; VEGFR2 expression as well as micro-vessel density (MVD) using CD31 were estimated in tumor tissues. Stem cell transplantation to mice bearing breast tumors resulted in tumor growth suppression in all experimental groups. The endothelial markers; CD31 and VEGFR2 were down regulated following I.T delivery of the endothelial cells. Accordingly, angiogenesis was suppressed following I.T administration of endothelial cells which was associated with increased focal necrosis in the tumors. In conclusion, data show that endothelial cells directly injected into tumors is more efficient compared to undifferentiated MSCs in controlling tumor-associated angiogenesis and tumor growth. | Authentic |
Text : Recently, the roles of circular RNAs (circRNAs) in tumor progression have attracted much attention. Currently, circ-SMAD7 has been identified as an oncogene in cancers. The aim of this study was to investigate the function of circ-SMAD7 in the progression of ovarian cancer. Circ-SMAD7 expression in both ovarian cancer cells and tissue samples was detected by quantitative Real Time-Polymerase Chain reaction (qRT-PCR). Circ-SMAD7 shRNA was constructed and transfected into the ovarian cancer cells. To identify the function of circ-SMAD7 in ovarian cancer, cell proliferation assay, colony formation assay, transwell assay, and Matrigel assay were conducted, respectively. In addition, qRT-PCR and Western blot assays were performed to elucidate the underlying mechanism and, then, it was analyzed. Circ-SMAD7 expression was remarkably higher in ovarian cancer tissue samples than in corresponding normal tissues. The proliferation of the ovarian cancer cells was significantly inhibited after circ-SMAD7 downregulation. Meanwhile, the migration and invasion of ovarian cancer cells were significantly inhibited after circ-SMAD7 downregulation in vitro. Both the mRNA and the protein expressions of the Krüppel-like factor 6 (KLF6) were remarkably promoted after circ-SMAD7 was knocked down in ovarian cancer cells. Furthermore, the KLF6 expression level was negatively correlated with circ-SMAD7 expression level in ovarian cancer samples. Our study suggests that circ-SMAD7 promotes the progression of ovarian cancer and enhances cell metastasis and proliferation via suppressing KLF6. In addition, circ-SMAD7 may be a novel therapeutic strategy in ovarian cancer. | Counterfeit |
Text : The associations of vegetable and fruit intake with liver cancer risk have been inconsistent based on epidemiological studies. The present study aimed to quantitatively evaluate these associations with prospective cohort studies. A systematic literature search was performed with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks (RRs) with a corresponding 95% confidence interval (CI) for the highest versus lowest category were pooled by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Dose-response analysis was conducted by using the variance weighted least squares regression model. Nine independent prospective cohort studies with 1703 liver cancer events and 1 326 176 participants were included for data synthesis. The summary estimates showed that higher vegetable intake was associated with a 39% (95%CI: 0.50, 0.75) reduction in liver cancer risk, with no significant between-study heterogeneity (P = 0.057). Dose-response analysis indicated that the risk of liver cancer was reduced by 4% (95%CI: 0.97, 0.95; P for trend <0.001) with a 100 gram per day increment of vegetable intake. Subgroup analysis showed that higher intakes of vegetables were associated with a 50% (95%CI: 0.35, 0.72) reduction of liver cancer risk in males, but not in females. However, a non-significant association was found between fruit intake and liver cancer risk. The present study provides strong evidence that higher intakes of vegetables would have beneficial effects on the prevention of liver cancer, especially for males. | Authentic |
Text : Background: Myocardial infarction (MI) is a serious condition, caused by acute, persistent ischemia or hypoxia of a coronary artery and responsible for heart failure and sudden death. This study aimed to investigate the effects of catechin, one of the main active components of green tea, on hypoxia-induced MI cell model, as well as the underlying possible mechanism. Methods: Cell viability, proliferation, apoptosis, and the expression of microRNA-92a (miR-92a) after hypoxia stimulation and/or catechin treatment were assessed using cell counting kit-8 (CCK-8) assay, western blotting, annexin V-FITC/PI staining and qRT-PCR, respectively. miRNA transfection was performed to change the expression of miR-92a. The effects of miR-92a on hypoxia and catechin-treated H9c2 cell viability, proliferation and apoptosis were evaluated. Finally, western blotting was conducted to measure the expression of core factors in the c-Jun N-terminal kinase (JNK) signaling pathway. Results: Hypoxia stimulation significantly inhibited H9c2 cell viability and proliferation, induced cell apoptosis and up-regulated miR-92a expression. Catechin markedly protected H9c2 cells from hypoxia-induced viability loss, proliferation inhibition, and apoptosis enhance, as well as miR-92a expression increase. Furthermore, suppression of miR-92a enhanced the protective effects of catechin on hypoxia-induced H9c2 cells. Overexpression of miR-92a had opposite effects. Catechin activated the JNK pathway in H9c2 cells by down-regulating miR-92a. Conclusion: Catechin protected H9c2 cells from hypoxia-induced injury by regulating miR-92a and JNK signaling pathway. Our findings facilitate the understanding of the protective activity of catechin in hypoxia-induced MI cell injury and provide a theoretical basis for further explore treatment of MI by using catechin. | Counterfeit |
Text : Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified clear. To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro. Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell fatty acid oxidation (FAO) via increasing NADP+/NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC. | Counterfeit |
Text : Gastric cancer (GC) is one of the most prevalent cancers worldwide. Trastuzumab has been approved for the treatment of metastatic GC, gastroesophageal junction cancer, and breast cancer. However, the mechanisms involved in trastuzumab-induced GC cell apoptosis remain largely unknown. In this study, we investigated the underlying mechanisms of trastuzumab-mediated suppression of GC cell growth both in vitro and in vivo. We found that trastuzumab treatment induces p53 upregulated modulator of apoptosis (PUMA) expression in GC cells, through the NF-κB pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. We also observed that PUMA was necessary for trastuzumab-induced apoptosis in GC cells. Moreover, PUMA deficiency suppressed apoptosis and the antitumor effect of trastuzumab in xenograft models. Finally, computerized tomography (CT) and immunohistochemistry results showed that patients with increased activation of PUMA were more sensitive to trastuzumab treatment than those with low PUMA expression. These results indicate that trastuzumab induces PUMA-dependent apoptosis and inhibits tumor growth in GC, suggesting that PUMA plays a critical role in mediating the antitumor effects of trastuzumab in GC. PUMA induction may be used as a marker of trastuzumab sensitivity. | Counterfeit |
Text : MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma. MSCTRAIL were radiolabelled with 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo. MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections. 89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability. | Authentic |
Text : Drug resistance is an obstacle to effective treatment of ovarian cancer. There have been substantial evidences supporting the association between diabetes and the sensitivity to chemotherapy. Insulin (INS) is believed to be the strongest, most lasting hypoglycemic drug. Therefore, the present study aimed to elucidate whether insulin could facilitate the anti‑proliferative activities of cisplatin (cis‑diamminedichloroplatinum, DDP) in the A2780 ovarian cancer cell line. The inhibitory effects of DPP with/without INS on the growth of A2780 cells was measured by MTT assay. The cell cycle stages and levels of apoptosis were determined by flow cytometry. The amounts of signaling elements involved in the regulation of were examined using western blotting and reverse transcription‑quantitative polymerase chain reaction analysis. The results indicated that INS pre‑treatment enhanced the inhibitory effect of DDP on the proliferation of A2780 cells, and facilitated the apoptosis induced by DDP. INS‑DDP treatment led to a marked decrease in the percentage of G0/G1 phase cells, but a corresponding increase in the proportion of S phase cells. Furthermore, A2780 cells pretreated with INS followed by DDP upregulated the protein expression level of phosphorylated c‑Jun N‑terminal kinase (JNK), which resulted in a substantial increase in the expression levels of p53 mRNA and protein, compared with DDP administration alone. In conclusion, the combination of INS and DDP facilitated the apoptosis of A2780 cells, which may be associated with the activation of the JNK signaling pathway and consequently the involvement of p53 at both mRNA and protein expression levels. These results may be useful in furthering our understanding of the mechanisms involved in the chemotherapeutic treatment of ovarian cancer. | Authentic |
Text : BACKGROUND Recent studies have illustrated that the transcription co-repressor, C-terminal binding protein 1 (CtBP1), links the metabolic alterations to transcription controls in proliferation, EMT, genome stability, metabolism, and lifespan, but whether CtBP1 affects the cellular redox homeostasis is unexplored. This study was designed to investigate the mechanism of CtBP1-mediated transcription repression that contributes to the metabolic reprogramming. MATERIAL AND METHODS Knockdown of CtBP1 in both mouse MEF cells and human melanoma cells changed cell redox homeostasis. Further, chromatin immunoprecipitation (ChIP) and luciferase reporter assay were performed for identification of CtBP1 downstream targets, pyruvate carrier 1 and 2 genes (MPC1 and MPC2), which contribute to redox homeostasis and are transcriptionally regulated by CtBP1. Moreover, blockage of the cellular NADH level with the glycolysis inhibitor 2-Deoxy-D-Glucose (2-DG) rescued MPC1 and MPC2 expression. MTT assay and scratch assay were performed to investigate the effect of MPC1 and MPC2 expression on malignant properties of melanoma cells. RESULTS The data demonstrated that CtBP1 directly bound to the promoters of MPC1 and MPC2 and transcriptionally repressed them, leading to increased levels of free NADH in the cytosol and nucleus, thus positively feeding back CtBP1's functions. Consequently, restoring MPC1 and MPC2 in human tumor cells decreases free NADH and inhibits melanoma cell proliferation and migration. CONCLUSIONS Our data indicate that MPC1 and MPC2 are principal mediators that link CtBP1-mediated transcription regulation to NADH production. The discovery of CtBP1 as an NADH regulator in addition to being an NADH sensor shows that CtBP1 is at the center of tumor metabolism and transcription control. | Authentic |
Text : Prostate cancer is a kind of malignancy with high occurrence in the male urogenital system. However, the mechanism of the occurrence, the progression, and the metastasis of prostate cancer are still unclear. Searching for the effective molecule target is of great significance to improve the curative effect on prostate cancer. Zinc finger E box binding protein-1 (ZEB1) protein is a member of the zinc finger transcription factor family that participates in the embryonic development and formation. ZEB1 was found to be involved in the occurrence and in the development of multiple cancers, while its role in prostate cancer still needs elucidation. Normal prostate cell line PC-3M and prostate cancer cell line DU145 were cultured in vitro and transfected by ZEB1 siRNA. ZEB1 mRNA and protein expressions were detected by real-time PCR and Western blot assay. Cell proliferation was determined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration was evaluated by transwell assay. Cell apoptosis was evaluated by caspase-3 activity. The impact of ZEB1 on extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway was assessed by Western blot assay. ZEB1 expression significantly increased in DU145 cells compared with PC-3M cells (p<0.05). ZEB1 mRNA and protein obviously declined, cell proliferation inhibited, cell invasion suppressed, and Caspase-3 activity enhanced in DU145 cells after ZEB1 siRNA transfection (p<0.05). ZEB1 siRNA markedly decreased ERK1/2 phosphorylation in DU145 cells compared with control (p<0.05). Inhibition of ZEB1 promoted prostate cancer apoptosis, restrained proliferation, and suppressed invasion through down-regulating ERK1/2 signaling pathway. | Authentic |
Text : MicroRNAs (miRs) play critical roles in the development and malignant progression of human cancers. miR-148a has previously been found to inhibit the migration and invasion of breast cancer cells. However, the underlying mechanism of miR-148a in regulating the viability and migration of estrogen receptor (ER) α-positive breast cancer cells is still unknown. In this study, ERα-positive breast cancer MCF7 cells were treated with estradiol (E2). Data from MTT and wound healing assays showed that E2 treatment promoted the viability and migration of MCF7 cells. A bioinformatics analysis and luciferase reporter assay identified ERα as a direct target of miR-148a. Ectopic expression of miR-148a significantly decreased the protein expression of ERα (P<0.01), while knockdown of miR-148a significantly increased the ERα protein level in MCF7 cells (P<0.01). Furthermore, miR-148a overexpression significantly inhibited the E2-induced viability and migration of MCF7 cells (P<0.01), similar to the effect of silencing ERα. However, overexpression of ERα rescued the suppressed viability and migration caused by miR-148a upregulation. Finally, it was found that E2 treatment led to a significant decrease in the miR-148a level in MCF7 cells (P<0.01). These results suggest that miR-148a can suppress the E2-induced viability and migration of MCF7 breast cancer cells via inhibition of ERα protein expression, expanding the understanding of miR function in ERα-positive breast cancer. | Authentic |
Text : Metformin, a well-known antidiabetic drug, exhibits anticancer effect in a variety of cancers, including liver cancer. Plantamajoside (PMS), a phenylethanoid glycoside compound isolated from Plantago asiatica, is proved to possess anticancer effects, too. In our study, we hypothesized that PMS might promote metformin mediated anticancer effects on liver cancer. The half maximal inhibitory concentration (IC50) of metformin was evaluated by cell viability assay. The influence of PMS on proliferation, migration, invasion and apoptosis of metformin-treated cells was evaluated by BrdU incorporation assay, flow cytometry, western blot, wound scratch healing assay, transwell cell migration assay and immunofluorescence. A fasting/feeding mouse model was built to evaluate the influence of PMS on metformin sensitivity in vivo. PMS (2.5, 10 or 40 μg/mL) treatment reduced the IC50 of metformin under different glucose concentrations. PMS (10 μg/mL) promoted metformin (5 mm) induced apoptosis and autophagy, and inhibition on proliferation, migration and invasion of HepG2 and HuH-7 cells. In the fasting/feeding mouse model, PMS (50 mg/kg) promoted metformin (200 mg/kg) induced proliferation arrest and apoptosis in vivo. Meanwhile, PMS reduced the level of pAkt(ser473) and GSK3β(ser9) in HepG2 and HuH-7 cells. Restoration of Akt/GSK3β signaling by a constitutively activated myr-Akt1 abrogated the effects of PMS on metformin-treated liver cancer cells. Our results demonstrated that PMS promoted the anticancer effects of metformin on liver cancer in vitro and in vivo. | Authentic |
Text : Human bladder cancer is one of the common malignant tumors, and it mainly occurs in men. miR-182-5p, a member of miR-183 family, acts as tumor suppressor or oncogene in various kinds of tumors. In this study, we first investigate that the absence of miR-182-5p in human bladder cancer promotes tumor growth by regulating the expression of Cofilin 1, an actin modulating-protein. Human bladder tumor tissue specimens were collected to detect the expression of miR-182-5p and Cofilin 1 by qRT-PCR. Luciferase activity assay was performed to demonstrate the regulation of Cofilin 1 mRNA 3'UTR by miR-182-5p. Then, cell experiments were performed to analysis the effect of miR-182-5p/Cofilin 1 pathway on tumor cell proliferation, migration, invasion and colony forming efficiency. Finally, xenograft tumor models were established to evaluate the role of miR-182-5p in tumorigenesis abilities in vivo. qRT-PCR and Western blotting analysis showed that Cofilin 1 expression was up-regulated in both bladder cancer tissues and cell lines compared with normal. Luciferase activity assay showed that miR-182-5p specifically targets Cofilin 1 mRNA 3'UTR and represses the expression of Cofilin 1. Also, miR-182-5p inhibited bladder tumor cell proliferation, migration, invasion and colony forming efficiency. Furthermore, xenograft tumor model assay showed that miR-182-5p plays a negative role in bladder cancer tumorigenesis abilities in vivo. Present results suggest that miR-182-5p could inhibit human bladder tumor growth by repressing Cofilin 1 expression. Our findings may provide a new horizon for exploring therapeutic target of bladder cancer. | Authentic |
Text : Long noncoding RNAs (lncRNAs) act as an initial factor and promoter in different tumors as a kind of ncRNAs. The length of them is >200 nucleotides opposite small ncRNAs. Increasing researches have proved that dysregulation lncRNA has been implicated in tumorigenesis. Small nucleolar RNA host gene 20 (SNHG20), a member of lncRNAs, expresses frequently in cancer types, such as hepatocellular carcinoma, ovarian cancer, colorectal cancer, and bladder cancer, contributing to cancer development and progression by transcriptional or posttranscriptional modifications. Not only does this review show the recent published literature concerning the biological functions but also demonstrates molecular mechanisms of SNHG20 among above multiple malignancies and others. | Authentic |
Text : Our study aimed to explore the effects of long noncoding RNA (lncRNA)-ANCR on the invasion and migration of colorectal cancer (CRC) cells by regulating enhancer of zeste homolog 2 (EZH2) expression. CRC tissues and adjacent normal tissues were collected and CRC SW620 cells line and normal human intestinal epithelial cells (HIECs) were incubated. CRC SW620 cells line was transfected with ANCR-siRNA. The expressions of ANCR and EZH2 mRNA were measured by real-time quantitative polymerase chain reaction (RT-qPCR). EZH2 and trimethylation of H3K27 (H3K27me3) protein expressions were detected using Western blotting. The relationship between ANCR and EZH2 was determined through RNA pull-down and co-immunoprecipitation (co-IP) assays. Cell invasion and migration were determined by Trans-well and cell scratch assays. ANCR, EZH2 and H3K27me3 expressions were up-regulated in CRC tissues and SW620 cells (all P < 0.05). After transfected with ANCR-siRNA, SW620 cells showed decreased ANCR expression and EZH2 mRNA and protein expressions (all P < 0.05). According to the results of RNA pull-down and co-IP assays, ANCR could specifically bind to EZH2. The results of Trans-well and cell scratch tests showed that when ANCR expression was decreased, the invasion and migration abilities of SW620 cells significantly declined (both P < 0.05). In conclusion, these results suggest that lncRNA-ANCR could influence the invasion and migration of CRC cells by specifically binding to EZH2. | Counterfeit |
Text : Prostate cancer (PC), the most commonly diagnosed malignancy, is also the second leading cause of cancer-related deaths. Although tremendous efforts have been achieved to improve the early detection of PC, it is still urgent to find out novel markers and therapeutic targets for PC patients. Homeobox protein MOX-1 (MEOX1) is found to be ectopically expressed in human cancers. This study aims to test the hypothesis that MEOX1 gene silencing might suppress the proliferation and invasion of LNCaP cells in PC. Microarray analysis was conducted to screen PC-related differentially expressed gene. MEOX1 was silenced to detect the relationship between silenced MEOX1 and cell proliferation, migration, apoptosis, and invasion. Expression of MEOX1, Bcl-2, p53, and Bax in LNCaP cells was determined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Cell proliferation, colony formation rate, cell migration, invasion, cell cycle, and apoptosis were detected respectively. MEOX1 gene was found to be expressed highly in PC tissues. After MEOX1 was silenced in LNCaP cells, the mRNA and protein expression of Bcl-2 decreased while the mRNA and protein expressions of p53 and Bax increased. Additionally, cell proliferation, migration, and invasion were reduced while cell apoptosis was increased by MEOX1, and MEOX1 gene silencing was revealed to inhibit cell proliferation and decrease tumorigenic ability of LNCaP cells in nude mice. Taken together, MEOX1 gene silencing could decrease the proliferation and increase apoptosis of LNCaP cells, and so it is expected to be a therapeutic target for PC. | Counterfeit |
Text : Adipocytes in the breast tumour microenvironment promotes acquired treatment resistance. We used an in vitro adipocyte-conditioned media approach to investigate the direct paracrine effects of adipocyte secretory factors on MDA-MB-231 breast cancer cells treated with doxorubicin to clarify the underlying treatment resistance mechanisms. Cell-viability assays, and Western blots were performed to determine alterations in apoptotic, proliferation and lipid metabolism protein markers. Free fatty acids (FFA) and inflammatory markers in the collected treatment-conditioned media were also quantified. Adipocyte secretory factors increased the cell-viability of doxorubicin-treated cells (p < 0.0001), which did not correspond to apoptosis or proliferation pathways. Adipocyte secretory factors increased the protein expression of hormone-sensitive lipase (p < 0.05) in doxorubicin-treated cells. Adipocyte secretory factors increased the utilization of leptin (p < 0.05) and MCP-1 (p < 0.01) proteins and possibly inhibited release of linoleic acid by doxorubicin-treated cells (treatment-conditioned media FFA profiles). Adipocyte secretory factors induced doxorubicin treatment resistance, by increasing the utilization of inflammatory mediators and inhibiting the release of FFA by doxorubicin-treated cells. This further promotes inflammation and lipid metabolic reprogramming (lipid storage) in the tumour microenvironment, which breast cancer cells use to evade the toxic effects induced by doxorubicin and confers to acquired treatment resistance. | Authentic |
Text : Cancerous inhibitor of protein phosphatase 2A (CIP2A) has been identified as an oncoprotein that is able to promote the proliferation of cancer cells. The role of CIP2A in the anticancer activity of bortezomib in colon cancer remains to be elucidated. In the present study, the antitumor effect of bortezomib was investigated and the role of CIP2A in determining the effect on colon cancer cells was identified. In the present study, bortezomib demonstrated an antitumor effect, as observed by WST‑1 assay and flow cytometry. In addition, the mRNA and protein level of CIP2A was inhibited in a dose‑dependent manner by bortezomib with quantitative PCR (qPCR) and western blotting. Furthermore, the inhibition of CIP2A with small interfering RNA by treatment with bortezomib inhibited proliferation, increased apoptosis and attenuated the invasion of the cells. Finally, the in vivo data demonstrated that bortezomib was able to decrease the growth of tumors, and that CIP2A was downregulated in the LoVo tumors treated with bortezomib. Therefore, CIP2A was shown to be important in the bortezomib‑induced inhibitory effect on colon cancer. | Authentic |
Text : Maintaining the balance between eliciting immune responses against foreign proteins and tolerating self-proteins is crucial for maintenance of homeostasis. The functions of programmed death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body cells. However, cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and proliferation. Over the past few years' rapid development in cancer immunotherapy has opened a new avenue in cancer treatment. Blockade of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high efficacy. Initially, immune checkpoint monotherapies were not very successful, making breast cancer less immunogenic. Although, recent reports support the presence of tumor infiltrating lymphocytes (TILs) in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy, which is effective in PD-L1 positive patients. Recently, anti-PD-1 (pembrolizumab) and anti-PD-L1 (atezolizumab) gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further research. Likewise, this article gathered understanding of PD-1 and PD-L1 in recent years, their signaling networks, interaction with other molecules, regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment efficacy. Additionally, authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy. | Authentic |
Text : The purpose of this work is to evaluate whether human microRNA-3129 (hsa-miR-3129) may functionally regulate cancer development, possibly through downstream target CD44 in human epithelial ovarian cancer (EOC). Direct targeting of hsa-miR-3129 on human CD44 transcript was evaluated using a dual-luciferase reporter assay. Gene expression of hsa-miR-3129 in immortal EOC cell lines was evaluated by qRT-PCR. Lentivirus-mediated hsa-miR-3129 upregulation or downregulation was conducted in SK-OV-3 and CAOV-3 cells, in which endogenous hsa-miR-3129 and CD44 expressions were then measured. In hsa-miR-3129 upregulated or downregulated EOC cells, functional assays were applied to evaluate EOC proliferation, bufalin chemoresistance in vitro, or xenotransplantation in vivo. Moreover, CD44 was ectopically overexposed in hsa-miR-3129 upregulated EOC cells to functionally evaluate the correlation between hsa-miR-3129 and CD44 in EOC. Dual-luciferase reporter assay confirmed hsa-miR-3129 directly binds CD44. QRT-PCR revealed that hsa-miR-3129 was substantially downregulated in EOC cell lines. In SK-OV-3 and CAOV-3 cells, lentivirus-induced hsa-miR-3129 upregulation downregulated CD44 whereas hsa-miR-3129 downregulation did not affect CD44 expression. Hsa-miR-3129 upregulation had significant anti-cancer effects by inhibiting EOC proliferation, increasing bufalin chemoresistance, and suppressing xenotransplantation. On the other hand, overexpressing CD44 reversed the anti-cancer functions by hsa-miR-3129 upregulation in EOC cells. In conclusion, Has-miR-3129 is a functional regulator, possibly through reverse targeting on CD44, in EOC. | Authentic |
Text : Human antigen R (HuR), also known as ELAVL1, is a widely expressed RNA-binding protein (RBP) that has a significant impact on the development and advancement of tumors. Our previous study found that 5-fluorouracil (5-FU) may impede the proliferation and increase apoptosis in gastric cancer cells by reducing the nucleocytoplasmic shuttling of HuR. However, how posttranscriptional regulation influences HuR functions in gastric cancer remains to be elucidated. Here, we demonstrated that miR-325-3p has the potential to regulate the expression level of HuR by directly binding to its 3'UTR, which in turn led to a significant reduction in proliferation and an increase in apoptosis in gastric cancer cells. In addition, xenograft experiment showed that knockdown of HuR or overexpression of miR-325-3p group exhibited smaller tumor sizes after transplant of gastric cancer cells into zebrafish larvae. Thus, our findings offer new insights into the pathogenesis of gastric cancer and may potentially assist in identifying novel targets for drug therapy. | Authentic |
Text : Urothelial cancer associated 1 (UCA1) as an oncogenic long non-coding RNA (LncRNA) was aberrantly upregulated in various solid tumors. Numerous studies have demonstrated overexpression of UCA1 is an unfavorable prognostic indicator in cancer patients. This study aimed to further explore the prognosis role and clinical significance of UCA1 in cancer. Eligible studies were recruited by a systematic search in PubMed, Embase, Cochrane Library and Web of Science databases. A total of 19/16 studies with 1587/1291 cancer patients were included to evaluate the association between UCA1 expression and overall survival (OS) and clinicopathological factors of malignancies by computing hazard ratio (HR), odds ratios (OR) and confidence interval (CI). The meta-analysis indicated overexpression of UCA1 was significantly correlated with unexpected OS in patients with cancer (pooled HR = 1.85, 95% CI 1.62-2.10, p < 0.001). There was also a significantly negative association between high level of UCA1 and poor grade cancer (pooled OR = 2.74, 95% CI 2.04-3.70, p < 0.001) and positive lymphatic metastasis (pooled OR = 2.43, 95% CI 1.72-3.41, p < 0.001). In conclusion, our study suggested that UCA1 was correlated with more advanced clinicopathological features and poor prognosis as a novel predictive biomarker of patients with various tumors. | Authentic |
Text : Many malignant cancers have an increased demand for lipoprotein due to the requirement for lipids for the rapid proliferation of the tumours and which is met by the increased availability of LDL through upregulation of LDL transporters. This unique phenomenon is the basis for the use of LDL based nanoparticles for cell imaging. In this study, a novel MR-active LDL nanoparticle was synthesised as the MRI probes. This MR-active LDL was characterised by using different techniques including scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infra-red spectroscopy (FTIR) and magnetic resonance imaging (MRI). The intracellular uptake of Gd3+ and cytotoxicity was measured by ICP-AES and MTT assay respectively. Results suggest that this nanoprobe with spherical shape and size of 55 nm has reduced relaxation time compared to commercial contrast agent and is introduced as an appropriate imaging probe. The amount of reabsorption of nanoprobe increased up to 6 h and given that the connection of the chelator does not have an effect on reabsorption proves that entry through transporter of APO section has done. This study lays the basis for exploring a personalised medicine strategy by directing a patient's own LDL to cancer cell imaging in the early stages. | Authentic |
Text : MicroRNAs (miRNAs) are increasingly recognized as important regulators of non-small cell lung cancer (NSCLC) progression by directly regulating their target genes. The aim of the present study was to assess the biological role of miR-19a-3p in NSCLC. It was revealed that miR-19a-3p expression was significantly downregulated in human NSCLC tissues and cell lines compared with normal tissues and lung epithelial cells. In addition, a lower miR-19a-3p expression was significantly associated with Tumor Node Metastasis stage and lymph node metastasis. Furthermore, the upregulation of miR-19a-3p in NSCLC cell lines significantly inhibited cell proliferation, migration and invasion, as determined using an MTT, colony formation, wound healing and transwell Matrigel invasion assays, respectively. A luciferase reporter assay and western blotting determined that ubiquitin associated protein 2 like (UBAP2L) was a direct target of miR-19a-3p and could be inhibited through the upregulation of miR-19a-3p in NSCLC. In addition, UBAP2L silencing induced similar effects to those observed following miR-19a-3p overexpression. The overexpression of UBAP2L partially reversed the effects of miR-19a-3p on NSCLC cell lines. Collectively, these data indicated that miR-19a-3p may serve as a tumor suppressor partly through the regulation of UBAP2L expression in NSCLC and that the targeting of miR-19a-3p may be a novel method for NSCLC treatment. | Counterfeit |
Text : This study aimed to investigate the role and the possible mechanism of the long noncoding small nucleolar RNA host gene 16 (SNHG16) in bladder cancer development. The expression of SNHG16 in the tumor tissues and plasma of patients with bladder cancer as well as bladder cancer cell lines was detected. T24 cells were then transfected with sh-SNHG16 to further investigate the effects of suppression of SNHG16 on T24 cell proliferation, apoptosis, migration, and invasion. In addition, the regulatory relationships between SNHG16 and miR-98 as well as the target of miR-98 were explored. Besides, the association between SNHG16 and the Wnt/β-catenin pathway was further elucidated. The SNHG16 expression was upregulated in the tumor tissues and plasma of patients with bladder cancer, as well as bladder cancer cells. Suppression of SNHG16 inhibited T24 cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro. In addition, SNHG16 negatively regulated miR-98 expression and regulated the malignant behaviors of T24 cells through sponging miR-98. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a functional target of miR-98, and miR-98 regulated the malignant behaviors of bladder cancer cells by targeting STAT3. Besides, suppression of SNHG16 inhibited the activation of the Wnt/β-catenin pathway, which was further regulated by miR-98 and STAT3, indicating that the effects of SNHG16/miR-98/STAT3 on T24 cells were achieved through the Wnt/β-catenin pathway. Our findings reveal that long noncoding RNAs SNHG16 is upregulated in bladder cancer and contributes to the development of bladder cancer possibly via regulating the miR-98/STAT3/Wnt/β-catenin pathway axis. The SNHG16/miR-98/STAT3/Wnt/β-catenin pathway axis may provide a new strategy for bladder cancer treatment. | Counterfeit |
Text : Turmeric extracts contain three primary compounds, which are commonly referred to as curcuminoids. They are curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin. While curcumin has been the most extensively studied of the curcuminoids, it suffers from low overall oral bioavailability due to extremely low absorption as a result of low water solubility and instability at acidic pH, as well as rapid metabolism and clearance from the body. However, DMC, which lacks the methoxy group on the benzene ring of the parent structure, has much greater chemical stability at physiological pH and has been recently reported to exhibit antitumor properties. However, the treatment of noncancerous diseases with DMC has not been comprehensively reviewed. Therefore, here we evaluate published scientific literature on the therapeutic properties of DMC. The beneficial pharmacological actions of DMC include anti-inflammatory, neuroprotective, antihypertensive, antimalarial, antimicrobial, antifungal, and vasodilatory properties. In addition, DMC's ability to ameliorate the effects of free radicals and an environment characterized by oxidative stress caused by the accumulation of advanced glycation end-products associated with diabetic nephropathy, as well as DMC's capacity to inhibit the migration and proliferation of vascular smooth muscle cells following balloon angioplasty are also addressed. This review collates the available literature regarding the therapeutic possibilities of DMC in noncancerous conditions. | Authentic |
Text : Circular RNA (circRNA) circ_POLA2 is an oncogene in lung and cervical cancers. However, the role of circ_POLA2 in other types of cancer is unknown. The present study investigated the role of circ_POLA2 in endometrial cancer (EC). The mRNA expression levels of circ_POLA2 and microRNA (miR)-31 in EC and paired adjacent normal tissues were analyzed using reverse transcription-quantitative (RT-qPCR). Overexpression of circ_POLA2 was achieved in the EC cell lines, and its effects on miR-31 mRNA expression level and methylation were evaluated using RT-qPCR and methylation-specific PCR (MSP), respectively. Cell proliferation was assessed using a Cell Counting Kit-8 assay. The results indicated that circ_POLA2 was highly expressed in EC tissue and inversely correlated with miR-31 mRNA expression level. MSP analysis showed that circ_POLA2 overexpression increased miR-31 methylation and RT-qPCR analysis showed that circ_POLA2 overexpression decreased miR-31 mRNA expression level. Furthermore, circ_POLA2 overexpression also increased EC cell proliferation, while miR-31 overexpression decreased cell proliferation. Finally, circ_POLA2 overexpression reduced the effects of miR-31 overexpression. In conclusion, circ_POLA2 may increase miR-31 methylation of miR-31 in EC cells to promote cancer cell proliferation. | Authentic |
Text : The aim of the study is to investigate the expression of sphingosine kinase 1 (SPHK1) and vascular endothelial growth factor (VEGF) in patients with endometrial carcinoma and its clinical significance. The tissues of 86 cases of patients with endometrial carcinoma and 54 cases of patients with endometrial atypical hyperplasia were collected. The expression of SPHK1 and VEGF in the tissue was detected by immunohistochemistry. The expression of SPHK1 in patients with endometrial carcinoma was compared with the clinicopathological data. Results. 69 cases (82.1%) of endometrial carcinoma were positive for SPHK1, which was higher than 2 cases (3.7%) of endometrial atypical hyperplasia (P < 0.05). The VEGF expression in 54 patients (62.8%) with endometrial carcinoma was higher than that in 12 patients with endometrial atypical hyperplasia (22.2%) (P < 0.05). There was a positive correlation between SPHK1 and VEGF expressions in endometrial carcinoma (c = 0.595). The expression of SPHK1 in endometrial cancer patients was different in different pathological types, FIGO stages, lymph node metastasis, ER, and PR positive or not, and the difference between the two groups was significant (P < 0.05). There was no difference in age, degree of differentiation, and depth of myometrial infiltration (P < 0.05). The expression of SPHK1 in patients with endometrial carcinoma is increased, which is helpful for early detection of patients with endometrial carcinoma, and may play a synergistic role with VEGF in the pathogenesis and development of endometrial carcinoma. | Authentic |