text
stringlengths 323
3.81k
| label
stringclasses 2
values |
|---|---|
Text : Butyrate is produced by the fermentation of undigested dietary fibers and acts as the promising candidate for cancer treatment. However, the mechanism underlying sodium butyrate (NaB)-induced autophagy in colorectal cancer is not yet completely understood. The expressions of LC3-II protein and mRNA were detected by western blot and quantitative RT-PCR in colorectal cancer (CRC) cell lines HCT-116 and HT-29, respectively. Autolysosome formation was observed by transmission electron microscope. AMPK and LKB1 were inhibited by chemical inhibitor or siRNAs and confirmed by western blot. NaB elevated the protein and mRNA expressions of LC3 in a dose-dependent manner. NaB treatment increased the formation of autolysosome and expression of phosphorylated liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC). Treatment with compound C (an inhibitor of AMPK) and siRNA-mediated knockdown of AMPK and LKB1 significantly attenuated NaB-induced autophagy in CRC cells. Collectively, these findings indicated that LKB1 and AMPK are critical for NaB-mediated autophagy and may act as the novel targets for colorectal cancer therapy in the future. | Authentic |
Text : To investigate the possible clinical relevance of ICAM-1 molecule in patients with advanced non-small cell lung cancer (NSCLC) treated with radiotherapy. The expression of ICAM-1 was examined immunohistochemically on tissue specimens of 62 patients with pathologically confirmed NCSLC. The median age at diagnosis was 62 years (range 49-84) with a male predominance (87.8%). All patients had stage III disease at presentation. The median follow up was 15.5 months (range 7-44). Obtained expression data were weighted against clinical and pathological parameters. Thirty-seven patients (60%) had no ICAM-1 staining, 16 patients (26%) had weak staining, while 6 patients (10%) expressed moderate staining and only 3 patients (5%) showed strong ICAM-1 staining. Moderate and high expressions were mostly observed in adenocarcinomas and undifferentiated carcinomas (n=8), that are considered more aggressive than squamous cell carcinoma (n=1). The median overall survival (OS) was 15 months (range 11-20). There seemed to exist an inverse association between ICAM-1 expression and OS, since there was a trend in median survival in favor of no ICAM-1 expression (p=0.083). Moreover, in patients with no ICAM-1 expression, there was observed a statistically significant difference in OS, favoring the squamous cell subtype (p=0.006). Nevertheless, ICAM-1 expression did not confer any statistical significance regarding smoking status (p=0.128), metastatic potential (p=0.574) as well as with the site of metastasis (p=0.964). Our findings may serve as a helping resource for further investigations of ICAM-1 as a molecular marker that could characterize treatment response and survival of tumor subpopulations. | Authentic |
Text : The side effects of busulfan on male reproduction are serious, so fertility preservation in children undergoing busulfan treatment is a major worldwide concern. Human placental mesenchymal stem cells (hPMSCs) have advantages such as stable proliferation and lower immunogenicity that make them an ideal material for stimulating tissue repair, especially restoring spermatogenesis. The protective effects of hPMSCs in busulfan-induced Sertoli cells and in busulfan-treated mouse testes have not been determined. Our study aimed to elaborate the protective effect and potential mechanisms of hPMSCs in busulfan-treated testes and Sertoli cells. First, we developed a mouse model of busulfan-induced testicular toxicity in vivo and a mouse Sertoli cell line treated with busulfan in vitro to assess the protective effect and mechanisms of hPMSC treatment on spermatogenesis. Then, the length, width, and weight of the testes were monitored using Vernier calipers. Furthermore, at 1 week and 4 weeks after the transplantation of hPMSCs, histological sections of testes were stained with hematoxylin-eosin, and the seminiferous tubules with fluid-filled cavities were counted. Through ELISA analysis, testosterone levels and MDA, SOD, LDH, and CAT activities, which are associated with ROS, were detected. Markers of ROS, proliferation (Ki67), and apoptosis (Annexin V) were evaluated by FACS. Next, the fluorescence intensity of proliferation markers (BrdU and SCP3), an antioxidant marker (SIRT1), a spermatogenesis marker (PLZF), and autophagy-related genes (P62 and LC3AB) were detected by fluorescence microscopy. The mRNA expression of γ-H2AX, BRCA1, PARP1, PCNA, Ki67, P62, and LC3 was determined by qRT-PCR. hPMSCs restored disrupted spermatogenesis, promoted improved semen parameters, and increased testosterone levels, testis size, and autophagy in the testis toxicity mouse model induced by busulfan. hPMSCs suppressed the apoptosis of Sertoli cells and enhanced their rate of proliferation in vitro. Additionally, hPMSCs protected against oxidative stress and decreased oxidative damage in the testis toxicity mouse model induced by busulfan. Furthermore, hPMSCs increased the expression of proliferation genes (PCNA and KI67) and decreased the mRNA levels of apoptotic genes such as γ-H2AX, BRCA1, and PARP1. This research showed that hPMSC injection ameliorated busulfan-induced damage in the testis by reducing apoptosis/oxidative stress and promoting autophagy. The present study offers an idea for a new method for clinical treatment of chemotherapy-induced spermatogenesis. | Authentic |
Text : The biological functions of long noncoding RNAs (lncRNAs) in the glioma have gained much attention in recent researches. However, the deepgoing mechanism by which lncRNA regulates the gliomagenesis is still ambiguous. In this work, we found that lncRNA CASC11 was significantly up-regulated in the glioma specimens and cells, and the ectopic overexpression indicated the poor prognosis of glioma patients. CASC11 expression could be activated by the transcription factor SP1. In vivo and vitro, the knockdown of CASC11 impaired the proliferation, migration and tumor growth of glioma cells. In mechanical experiments, the miR-498 was found to target the 3'-UTR of lncRNA CASC11 and FOXK1 mRNA. Taken together, the data suggest the regulation of SP1/CASC11/miR-498/FOXK1 in the gliomagenesis, which might provide a potential therapeutic strategy for glioma. | Authentic |
Text : Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis. All patients with GISTs diagnosed at the University Hospital of Besançon between August 2005 and October 2014 were prospectively included in the present study. KIT, PDGFRA and KRAS-codons 12 and 13 as well as BRAF codon 600 mutations were analyzed by Sanger sequencing or SNaPshot. KIT and PDGFRA mutations were detected in 71.2 and 19.2% of the cases, respectively. A total of 43 different mutations were detected of which 13 had never been described. As expected, KIT exon 9 and PDGFRA exon 18 mutations were associated with small bowel and gastric localizations respectively. No mutation was found in KRAS and BRAF. Molecular studies are critical to improve the management of GISTs. Our study enhances the current knowledge by describing 13 new mutations in KIT. A common molecular pattern in all KIT exon 11 substitutions is also described for the first time in this study but its significance remains unknown since genetic and environmental risk factors favoring the development of GISTs such as DNA repair defects and exposure to carcinogens are not currently known. | Authentic |
Text : To study the influence of nursing model based on Rosenthal effect on self-efficacy and cognition of life meaning in patients with non-small-cell lung cancer (NSCLC). 120 patients with NSCLC treated in the hospital were selected from November 2020 to November 2021 and were randomly divided into the nursing group and the Rosenthal group, with 60 cases in each group. The nursing group received routine nursing intervention, while the Rosenthal group was intervened by nursing model based on the Rosenthal effect, and both groups were intervened for 1 month. The self-efficacy (General Self-Efficacy Scale (GSES)), negative emotions (Hospital Anxiety and Depression Scale (HADS)), self-burden (Self-Perceived Burden Scale for Cancer Patients (SPBS-CP)), meaning of life (Meaning of Life Scale for Advanced Cancer Patients (MiLS)), and quality of life (Functional Assessment of Cancer Therapy-Lung (FACT-L)) were compared between the two groups before and after intervention. After 1 month of intervention, the scores of GSES and MiLS of patients in the two groups were significantly higher than those before intervention, and the scores in the Rosenthal group were significantly higher than those in the nursing group (P < 0.05). The scores of HADS, SPBS-CP, and FACT-L in the two groups were significantly lower than those before intervention, and the scores were significantly lower in the Rosenthal group than those in the nursing group (P < 0.05). Nursing model intervention based on Rosenthal effect enhances the self-efficacy and meaning of life and reduces the negative emotions and self-burden in patients with NSCLC. | Authentic |
Text : Lung cancer has the highest mortality rate amongst human cancers and the majority of deaths can be attributed to metastatic spread. The miR-34 family includes three tumor suppressive miRs: miR-34a, miR-34b and miR-34c. miR-34 downregulation is a frequent observation in human malignancies and is often attributed to hypermethylation of the miR-34a and miR-34b/c promoters. Here, the potential association between aberrant miR-34 expression and promoter methylation and distant metastases formation in lung adenocarcinoma (LAC) is investigated. The expression levels of miR-34a, miR-34b and miR-34c, as well as the methylation status of the miR-34a and miR-34b/c promoters were determined in a LAC patient cohort comprising 26 non-metastasizing and 26 metastasizing primary LACs, as well as 24 paired distant metastases and 25 tumor-adjacent normal lung samples using RT-qPCR and Methylation-Sensitive High Resolution Melting (MS-HRM) analysis. No difference in expression was observed for miR-34a when comparing metastasizing and non-metastasizing LACs (p=0.793). For both miR-34b and miR-34c, a significantly lower expression level was determined in metastasizing LACs compared to non-metastasizing LACs (p=0.0005 and p=0.002) with similarly decreased expression levels observed in the paired distant metastases. Hypermethylation was detected in 35/51 LACs compared to 0/25 tumor-adjacent normal lungs for the miR-34a promoter (p<0.0001). Similarly, 18/51 LACs compared to 1/25 tumor-adjacent normal lungs showed hypermethylation of the miR-34b/c promoter (p=0.003). No difference in methylation was observed between metastasizing and non-metastasizing LACs for neither the miR-34a (p=0.832) nor the miR-34b/c (p=0.900) promoter. In conclusion, miR-34a and miR-34b/c promoter hypermethylation is a frequent event in LAC occurring in 68.7% and 35.3% of tested cases (n=51), respectively. Low miR-34b and miR-34c expression was associated with distant metastases formation in LAC. These changes can be targeted as novel biomarkers in LAC. | Authentic |
Text : Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. miR-455-5p has increased expression and the ability to promote tumorigenesis in certain cancers. However, the role of miR-455-5p in NSCLC has not been sufficiently investigated. SOCS3 (suppressor of cytokine signaling 3), an important tumor suppressor, is often aberrantly inactivated in various tumors, but it is currently unclear whether SOCO3 is a target of miR-455-5p. In the present study, we investigated the role of miR-455-5p in NSCLC. We found that the expression of miR-455-5p was up-regulated in NSCLC tumor tissues compared to corresponding noncancerous tissues, and its expression was correlated with metastasis and tumor node metastasis in NSCLC tissue. We then showed that miR-455-5p promoted migration, invasion and proliferation in NSCLC cell lines. Additionally, we also found that SOCS3 was the direct target gene of miR-455-5p. Consistently, the expression of SOCS3 was negatively correlated with the expression of miR-455-5p in NSCLC tissues. We further show that aberrant miR-455-5p expression is partially controlled by activated ERK signaling in NSCLC. Therefore, miR-455-5p could enhance the growth and metastasis of NSCLC by inhibiting SOCS3, thus providing a potential molecular therapeutic target for the treatment of NSCLC patients. | Authentic |
Text : The aim of the study is to investigate the role of pingyangmycin (PYM) in oral carcinoma (OC) cell autophagy via the PI3K/AKT/mTOR axis. 200 μL PYM culture solution with a concentration of 100 μg/ml (low PYM (L-PYM) group), 300 μg/ml (middle PYM (M-PYM) group), 500 μg/ml (high PYM (H-PYM) group), and the same amount of conventional medium (normal control (NC)) were added to the purchased OC cell line SCC-25, respectively, and the PI3K/AKT/mTOR pathway expression, autophagy protein levels, cell activity, and apoptosis rate were determined. Subsequently, we selected OC cells co-cultured with PYM with the concentration of the most significant intervention effect and 740Y-P, a specific activator of the PI3K/AKT/mTOR axis, and those treated with 740Y-P alone for the aforementioned detection. L-PYM, M-PYM, and H-PYM groups all showed decreased PI3K, AKT, mTOR, and phosphorylated protein levels (P < 0.05). Beclin1 and LC3-II protein levels and apoptosis rate of PYM-intervened OC cells increased, but the activity decreased (P < 0.05). Under 740Y-P intervention, the PI3K/AKT/mTOR pathway was activated, cell activity was increased, and the apoptosis rate and autophagy were decreased (P < 0.05). Simultaneous use of PYM and 740Y-P led to no difference in cell condition compared with NC (P > 0.05P>0.05). PYM can activate OC cell autophagy by inhibiting the phosphorylation of the PI3K/AKT/mTOR axis, and thus, achieving the goal of killing tumor cells. | Authentic |
Text : MicroRNAs (miRNAs) are endogenous, non-coding small RNAs, which play an important part in regulating organismal and pathological processes. Previous studies have shown that miRNA-199 acts as a tumor suppressor gene. However, we aimed to explore the characteristics and function of miRNA-199 in lung cancer (LCa), so as to further study its relationship with clinicopathological parameters and prognosis. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect miRNA-199 expression in 75 pairs of LCa tissues and normal adjacent tissues. In addition, the relationship between miRNA-199 expression and pathological features along with the prognosis of LCa patients were investigated. Besides, the expression level of miRNA-199 in LCa cells was further validated by qRT-PCR. In addition, miRNA-199 overexpression expression model was constructed in LCa cell lines H1299 and SPCA1. Cell counting kit-8 (CCK-8), cell cloning experiments, transwell invasion and migration assays were performed to analyze the effect of miRNA-199 on the biological function of LCa cells. Finally, the potential mechanism was explored using Western blot. qRT-PCR results displayed that the expression level of miRNA-199 in LCa tissues was significantly lower than that of the normal tissues. Compared with patients with high miRNA-199 expression, patients with lowly-expressed miRNA-199 had higher rates of lymph node metastases and distant metastases, and their overall survival rates were lower. In addition, the proliferation, invasion and metastasis of the miRNA-199 overexpression group were significantly increased than that in the negative control group. Western Blot results showed that the expression of key proteins in the EMT pathway, such as N-cadherin, Vimentin, β-catenin and MMP9 significantly increased in miRNA-199 overexpression group. Moreover, we also found that miRNA-199 and RGS17 have mutual regulation, which inhibited the malignant progression of LCa. miRNA-199 expression was down-regulated in LCa and was significantly associated with LCa stage, distant metastasis, and poor prognosis. Besides, miRNA-199 may inhibit the malignant progression of LCa by interacting with RGS17. | Authentic |
Text : Growth hormone receptor (GHR), a member of the class I cytokine receptor family, plays key roles in cancer progression. Recently, GHR has been reported to be associated with breast cancer development, but the molecular mechanism of GHR in this malignancy is not fully understood. To investigate this issue, we stably inhibited GHR in breast cancer cell lines, which were observed to reduce cell proliferation, tumor growth and induction of apoptosis, and arrest the cell-cycle arrest at the G1-S phase transition. In addition, GHR silencing suppressed the protein levels of B-Raf proto-oncogene, serine/threonine kinase (BRAF), Mitogen-activated protein kinase kinase (MEK) and Extracellular regulated protein kinases (ERK). These findings suggest that GHR may mediate breast cell progression and apoptosis through control of the cell cycle via the BRAF/MEK/ERK signaling pathway. | Authentic |
Text : Lymphocyte to monocyte ratio (LMR) has shown prognostic value in different types of cancer. This study assessed the prognostic performance of LMR in early-stage non-small cell lung cancer (NSCLC) patients and investigated the influence of LMR on the treatment response in patients receiving first-line platinum-based chemotherapy. Four hundred eighty-eight NSCLC patients and 500 healthy donors were enrolled in this study. The cutoff value for LMR was chosen by receiver operating characteristic curve analysis. The prognostic significance of markers was assessed by univariate and multivariate Cox regression models. The median overall survival was 43 months, and the median progression-free survival was 38 months. LMR was associated with disease status and the treatment response of first-line platinum-based chemotherapy. Multivariate analysis showed that LMR was an independent prognostic factor for both overall survival (hazard ratio = 1.53, 95 % confidence interval = 1.09-2.14, P = 0.015) and progression-free survival (hazard ratio = 1.20, 95 % confidence interval = 1.02-1.67, P = 0.028). Furthermore, integration of LMR into a prognostic model including TNM stage, tumor status, chemotherapy, and histological type generated a nomogram, which predicted accurately overall survival for NSCLC patients. Decreased LMR may be a potential biomarker of disease status, worse response to first-line platinum-based chemotherapy, and worse survival for NSCLC patients. A prospective study is warranted for further validation of our findings. | Authentic |
Text : MicroRNA (miR)‑30a‑5p has been reported to suppress the progression of hepatocellular cancer, renal cell carcinoma, oral cancer and gastric cancer. However, whether miR‑30a‑5p is involved in the regulation of melanoma remains unclear. The present study revealed that miR‑30a‑5p was downregulated in melanoma tissues and cell lines. Overexpression of miR‑30a‑5p significantly inhibited the proliferation, migration and invasion of melanoma cells in vitro. In addition, ectopic expression of miR‑30a‑5p delayed tumor growth in vivo. In terms of mechanism, miR‑30a‑5p targeted sex determining region Y‑box 4 (SOX4) and impeded the expression of SOX4 in melanoma cells. In addition, SOX4 was upregulated in melanoma tissues and cell lines when compared with normal tissues or cells. Furthermore, overexpression of SOX4 significantly rescued the proliferation, migration and invasion of melanoma cells transfected with miR‑30a‑5p mimics. Taken together, the results of the present study demonstrated that miR‑30a‑5p suppressed the proliferation, migration and invasion of melanoma cells in SOX4‑dependent manner. | Counterfeit |
Text : Lung adenocarcinoma (LAD) and lung squamous cell cancer (LSCC) are two most common histological types of lung cancer, while they differ in many aspects. Recent evidence shows that long non-coding RNAs (lncRNAs) play an important role in the process of cancer initiation and progression. Thus, characterization of LAD and LSCC associated lncRNAs may help understand the difference between LAD and LSCC. Here, we analyzed three sets of RNA-seq data, including LAD RNA-seq data from TCGA project. We identified a novel lncRNA, long intergenic non-protein coding RNA 1207 (LINC01207) which was significantly up-regulated in LAD tissues compared with paired non-tumor tissues (5.78 fold increase, P<0.05), while there was no significant differences between LSCC tissues and adjacent non-tumor tissues. The expression level of LINC01207 was associated with TNM stage of LAD patients, and higher LINC01207 level indicated advanced TNM stage (P<0.05) and shorter survival (HR=2.53, P<0.05). By small interfering RNA (siRNA) mediated knockdown of LINC01207, we determined the biological function of LINC01207 in A549 cell line. After knockdown of LINC01207, cell proliferation ability was inhibited. Further analysis showed that after silence of LINC01207, the percentage of apoptotic cells significantly increased. By RNA immunoprecipitation and Chromatin immunoprecipitation assay, we demonstrated that LINC01207 could bind with EZH2 and mediated trimethylation of histone 3 lysine 27 at the promoter region of Bad, an important pro-apoptotic gene. Finally, we developed xenograft tumor models in nude mice and xenograft tumors derived from A549 cells transfected with siRNA-LINC01207 had significantly lower tumor weight and smaller tumor volume. In summary, the novel lncRNA, LINC01207 is specifically up-regulated in LAD but not in LSCC; and LINC01207 could promote LAD cell growth both in vivo and in vitro. | Authentic |
Text : Evidence has suggested that salidroside inhibits the proliferation and invasion of renal clear cell, lung, breast, and colon cancer. However, effect of salidroside on colorectal cancer (CRC) cells against oxaliplatin (L‑OHP) resistance remains unclear. In the present study, the CRC HT‑29 cell line and L‑OHP resistance HT‑29/L‑OHP cell line were used to evaluate the effect, and mechanism of salidroside on L‑OHP resistance. The results demonstrated that the activity of HT‑29 cells was lower compared with that of HT‑29/L‑OHP cells following L‑OHP intervention, and was accompanied with varied expression levels of drug resistant proteins. The combination of salidroside and L‑OHP weakened cell activity significantly compared single utilization. Compared with the control group, salidroside intervention resulted in a higher percentage of HT‑29/L‑OHP cells in the G0/G1 stage, and reduced percentage in the G2/M stage, but no significant variation in the S stage. The HT‑29/L‑OHP cells exhibited increased apoptosis rates and caspase‑3 activity, but decreased metastatic, and invasive abilities following salidroside intervention. Quantitative polymerase chain reaction and western blot analysis detected variations in the expression levels of associated genes in HT‑29/L‑OHP cells following salidroside intervention. In all, the results of the present study revealed that salidroside is able to decrease the activity and invasive capacity of HT‑29/L‑OHP cells, and treatment with salidroside is associated with increased apoptosis of cancer cells through the regulation of certain genes. | Authentic |
Text : To detect the expression of microRNA-556-3p in esophageal cancer (EC) tissues and to elucidate the mechanisms underlying microRNA-556-3p in promoting EC progression. QRT-PCR (quantitative Real-Time Polymerase Chain Reaction) was performed to detect microRNA-556-3p expression in 65 cases of EC tissues, 30 cases of normal esophageal tissues and EC cell lines. The overall survival (OS) of EC patients was calculated based on the 10-year follow-up data. For in vitro experiments, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assay were performed to evaluate the effect of microRNA-556-3p on the proliferative and invasive abilities of EC cells. The effect of microRNA-556-3p on DAB2IP and MAPK pathway was determined by Western blot and qRT-PCR. The binding condition between microRNA-556-3p and DAB2IP was further confirmed by Luciferase reporter gene assay. MicroRNA-556-3p expression was upregulated in EC tissues than that of paracancerous tissues. EC patients with higher expression of microRNA-556-3p presented a shorter OS than those with lower expression. Moreover, microRNA-556-3p overexpression in EC cells remarkably promoted cell viability. Upregulated microRNA-556-3p in Eca109 and Eca7906 cell lines markedly increased cell proliferation and invasion. The expression level of DAB2IP was negatively regulated by microRNA-556-3p verified by the Luciferase reporter gene assay. MicroRNA-556-3p blocked the translation of DAB2IP at mRNA level by directly binding to 3'UTR of DAB2IP, thereafter enhancing the proliferation of Eca109 and Eca7906 cells. MicroRNA-556-3p promoted the occurrence and development of EC. Our study provided a new theoretical basis and therapeutic target for EC treatment. | 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 : Early detection is critical for the treatment of colon carcinoma. However, current biomarkers for its diagnosis and prognosis are insufficient and improvement is required. Aberrantly expressed microRNAs (miRNAs/miRs) in colon carcinoma have been identified to function as potential diagnostic and prognostic biomarkers. In the present study, 245 differentially expressed miRNAs between colon carcinoma and normal tissues were identified by a bioinformatics analysis of a dataset from The Cancer Genome Atlas. A six‑miRNA (miR‑149, miR‑3189, miR‑3677, miR‑3917, miR‑4999 and miR‑6854) prognostic prediction system was established, which is able to independently and effectively predict the prognosis of colon carcinoma patients [P<0.001, area under the receiver operating characteristic curve (AUC)=0.763]. Furthermore, the six miRNAs were highly correlated with the tumor‑nodes‑metastasis (TNM) stage and were able to distinguish between different stages (high vs. low TNM stage, P<0.001). Of note, combination of the six‑miRNA signature and TNM stage provides an improved prediction of the patient's prognosis (AUC=0.797). Functional enrichment analysis revealed the possible mechanistic involvement of these predictive miRNAs in cancer‑associated biological processes and pathways. Taken together, the present study demonstrated the promising potential of the novel six‑miRNA model as an independent factor for the prediction of the progression and prognosis of colon carcinoma. | Authentic |
Text : Melanoma is the most common skin cancer and malignant melanoma which can cause skin cancer-related deaths. Toll-like receptor 4 (TLR4) had been reported to play an important role in melanoma, and tea polyphenol (TP) is regarded as an anticancer substance. However, the relationship between TP and TLR4 in melanoma is not well explored. Therefore, our aim is to figure out how TP has an influence on melanoma. Melanoma cell lines (B16F10 and A375) were treated with TP and lipopolysaccharides (LPS). Western blot assay was used to examine TLR4 expression, and MTT assay was conducted to assess proliferation. Wound healing assay was conducted to evaluate the migration of melanoma cells, and transwell assay was used to examine the melanoma cells' invasiveness. Besides, in vivo experiments were practiced for TP function in mice with melanoma cells. TP inhibited the proliferation, migration and invasion ability of melanoma cells, which displayed a dosage and time dependence. TLR4 was highly expressed in melanoma cells compared with normal skin cells. TP could suppress TLR4 expression both in normal melanomas and in stimulated melanomas by TLR4 agonist LPS. Suppressing TLR4 in melanomas could inhibit cell function (proliferation, migration, and invasion), and blocking the expression of 67LR could abolish TP function on TLR4. TP can inhibit melanoma (B16F10) growth in vivo. | Authentic |
Text : Didscoidin domain receptor 1 (DDR1) is involved in the progression of prostate cancer metastasis through stimulation of epithelial-mesenchymal transition (EMT). So DDR1 inhibition can be a helpful target for cancer metastasis prevention. So, we studied the effects of DDR1 inhibition on EMT as well as induction of cell-cycle arrest and apoptosis in prostate cancer cell lines. DDR1 expression was evaluated using reverse-transcription polymerase chain reaction and western blot analysis. The EMT-associated protein expression was determined using the western blot analysis and immunocytochemistry following treatment with various concentrations of DDR1 inhibitor. The activation of DDR1 and also downstream-signaling molecules Pyk2 and MKK7 were determined using western blot analysis. Cell survival and proliferation after DDR1 inhibition were evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide, bromodeoxyuridine, and colony formation assays. Flow cytometry analysis was used to determine the effects of DDR1 inhibition on cell-cycle arrest and apoptosis using annexin V/propidium iodide-based flow cytometry. Results showed that the protein expression of N-cadherin and vimentin were decreased whereas protein expression of E-cadherin was increased after DDR1 inhibition. Results of our western blot analysis indicated that DDR1 inhibitor effectively downregulated P-DDR1, P-Pyk2, and P-MKK7 levels. This result also showed that DDR1 inhibition decreased cell survival and proliferation, induced G1 cell-cycle arrest, induced apoptosis by an increase in the Bax/Bcl-2 ratio and depletion of the mitochondrial membrane potential, and also by reactive oxygen species creation in prostate cancer cells. These data show that DDR1 inhibition can result in the EMT prevention via inhibition of Pyk2 and MKK7 signaling pathway and induces cell-cycle arrest and apoptosis in prostate cancer cell lines. Thus, this study identifies DDR1 as an important target for modulating EMT and induction of apoptosis in prostate cancer 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 : Rectal cancer, defined as a cancerous lesion of the colon distal to the rectosigmoid junction, is the fourth most common cancer cause of death globally. There were 474 patients with rectal cancer who underwent surgery between October 2007 and May 2013 enrolled in our center. Patients were respectively categorized by neoadjuvant therapy. This study aimed to explore the predictive factors that affected the Progression-free survival and overall survival of the patients with rectal cancer. Clinical characteristics of patients were compared with the groups and potential prognostic factors were analyzed by SPSS 19.0. In our study, neoadjuvant therapy increased the anus-retained rate (64.4 vs 53.4 % P = 0.016) and remission rate in the treatment group, compared to the non-treatment group (62.6 vs 34.8 %; P = 0.000). The neoadjuvant concurrent chemoradiotherapy, more operative duration, anus retained and micturition damaged are positive prognostic factors of PFS to patients. Poor differentiation, the tumor of ulcer, invasive, and pT4 stage, contributed the poor factors for PFS of patients (P < 0.05). Additionally, the patients with neoadjuvant concurrent chemoradiotherapy and adjuvant chemotherapy underwent the better prognosis of OS. Adjuvant chemotherapy cannot increase PFS of the patients who accepted neoadjuvant therapy after surgery get pCR, but can improve OS. The anus-retained and neoadjuvant radiotherapy, duration of surgery in rectal cancer have the positive correlation. Micturition damaged and neoadjuvant radiotherapy were positively correlated as well. In conclusion, adjuvant chemotherapy does not improve the PFS of patients with pCR to neoadjuvant therapy, but is good for OS. Further prospective and large population-based clinical studies are needed to establish clinical guidelines for the use of neoadjuvant therapy and adjuvant chemotherapy in patients with rectal cancer. | Authentic |
Text : Cervical cancer (CC) is one of the leading causes of death in women due to cancer and a major concern in the developing world. Persistent human papilloma virus (HPV) infection is the major causative agent for CC. Besides HPV infection, genetic and epigenetic factors including microRNA (miRNA) also contribute to the malignant transformation. Earlier studies have revealed that miRNAs participate in cell proliferation, invasion and metastasis, angiogenesis, and chemoresistance processes by binding and inversely regulating the target oncogenes or tumor suppressor genes. Based on functions and mechanistic insights, miRNAs have been identified as cellular modulators that have an enormous role in diagnosis, prognosis, and cancer therapy. Signatures of miRNA could be used as diagnostic markers which are necessary for early diagnosis and management of CC. The therapeutic potential of miRNAs has been shown in CC; however, more comprehensive clinical trials are required for the clinical translation of miRNA-based diagnostics and therapeutics. Understanding the molecular mechanism of miRNAs and their target genes has been useful to develop miRNA-based therapeutic strategies for CC and overcome chemoresistance. In this review, we summarize the role of miRNAs in the development, progression, and metastasis of CC as well as chemoresistance. Further, we discuss the diagnostic and therapeutic potential of miRNAs to overcome chemoresistance and treatment of CC. | Authentic |
Text : Fangchinoline, an important compound in Stephania tetrandra S. Moore, as a novel antitumor agent, has been implicated in several types of cancers cells except gastric cancer. To investigate whether fangchinoline affects gastric cancer cells, we detected the signaling pathway by which fangchinoline plays a role in different human gastric cancer cells lines. We found that fangchinoline effectively suppressed proliferation and invasion of SGC7901 cell lines, but not MKN45 cell lines by inhibiting the expression of PI3K and its downstream pathway. All of the Akt/MMP2/MMP9 pathway, Akt/Bad pathway, and Akt/Gsk3β/CDK2 pathway could be inhibited by fangchinoline through inhibition of PI3K. Taken together, these results suggest that fangchinoline targets PI3K in tumor cells that express PI3K abundantly and inhibits the growth and invasive ability of the tumor cells. | Counterfeit |
Text : Fibrotic microenvironment has been reported to have a pro-metastasis effect on tumor cells, but the mechanism remains unclear. The current study aimed to explore the underlying mechanism by which the fibrotic microenvironment affects tumor cells. A tumor metastasis model was established by injecting tumor cells containing GFP into mice with pulmonary fibrosis. Lung tissues and fibroblasts were harvested, and conditioned medium (CM) were collected from fibrotic lungs and fibroblasts. Hematoxylin & eosin staining and immunohistochemistry were used to detect pulmonary metastasis and FSP1 expression, respectively. Bioinformatics and dual-luciferase reporter assay proved that the target genes of ZEB1-AS1 and miR-200b-3p were miR-200b-3p and ZEB1, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of GFP, ZEB1-AS1, and miR-200b-3p. Transwell assay, Annexin V/PI assay, and colorimetry were performed to examine the effects of CM, ZEB1-AS1, miR-200b-3p, and ZEB1 on cell invasion, apoptosis, and the activity level of caspase-3/-9. Pulmonary metastasis was promoted and the expressions of FSP1 and GFP were increased in mice with pulmonary fibrosis. CM enhanced the invasion and inhibited the apoptosis of tumor cells. SiZEB1-AS1 and siZEB1 inhibited the invasion and apoptosis of tumor cells, while miR-200b-3p inhibitor had the opposite effect of SiZEB1-AS1 and siZEB1, and further reversed the effect of siZEB1 on tumor cell invasion and apoptosis. SiZEB1-AS1 reversed the effects of both miR-200b-3p inhibitor and miR-200b-3p inhibitor+siZEB1 on tumor cell invasion and apoptosis. Fibrotic microenvironment promoted the metastatic seeding of tumor cells into the lungs via mediating the ZEB1-AS1/miR-200b-3p/ZEB1 signaling. | Authentic |
Text : Autism spectrum disorder is a severe, life-prolonged neurodevelopmental disease typified by disabilities that are chronic or limited in the development of socio-communication skills, thinking abilities, activities, and behavior. In children aged two to three years, the symptoms of autism are more evident and easier to recognize. The major part of the existing literature on autism spectrum disorder is covered by a prediction system based on traditional machine learning algorithms such as support vector machine, random forest, multiple layer perceptron, naive Bayes, convolution neural network, and deep neural network. The proposed models are validated by using performance measurement parameters such as accuracy, precision, and recall. In this research, autism spectrum disorder prediction has been investigated and compared using common parameters such as application type, simulation method, comparison methodology, and input data. The key purpose of this study is to give a centralized framework to use for researchers working on autism spectrum disorder prediction. The best results were obtained by using the random forest algorithm as it performs better than other traditional machine learning algorithms. The achieved accuracy is 89.23%. The workflow representations of the investigated frameworks assist readers in comprehending the fundamental workings and architectures of these frameworks. | Counterfeit |
Text : Treatment with immune checkpoint inhibitors has revolutionized cancer treatment over the past several years. Despite their clinical benefits, a wide range of immune-mediated toxicities can be observed including hematological toxicities. Although, the majority can easily be managed, immune-mediated adverse events rarely can be severe and difficult to approach. Herein, we are reporting a case of very severe aplastic anemia secondary to ipilimumab (I) and nivolumab (N) treatment that failed various treatment including intensive immune suppressive therapy. We described a case of a 45-year old white male, heavy smoker presented to the clinic complaining of left flank pain. He was found to have a metastatic renal cell carcinoma for which he was treated with dual immunotherapy and later complicated by severe immune related adverse events. The patient later died after failing intensive immune suppressive therapy. Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with variant malignancies. Yet, lethal adverse events can occur in rare cases. It is our duty, as physicians, to remain alert and cautious. | Authentic |
Text : Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children and Glucocorticoids (GCs) form an essential component of the standard chemotherapy in most treatment regimens. The category of infant ALL patients carrying a translocation involving the mixed lineage leukemia (MLL) gene (gene KMT2A) is characterized by resistance to GCs and poor clinical outcome. Although some studies examined GC-resistance in infant ALL patients, the understanding of this phenomenon remains limited and impede the efforts to improve prognosis. This study integrates differential co-expression (DC) and protein-protein interaction (PPI) networks to find active protein modules associated with GC-resistance in MLL-rearranged infant ALL patients. A network was constructed by linking differentially co-expressed gene pairs between GC-resistance and GC-sensitive samples and later integrated with PPI networks by keeping the links that are also present in the PPI network. The resulting network was decomposed into two sub-networks, specific to each phenotype. Finally, both sub-networks were clustered into modules using weighted gene co-expression network analysis (WGCNA) and further analyzed with functional enrichment analysis. Through the integration of DC analysis and PPI network, four protein modules were found active under the GC-resistance phenotype but not under the GC-sensitive. Functional enrichment analysis revealed that these modules are related to proteasome, electron transport chain, tRNA-aminoacyl biosynthesis, and peroxisome signaling pathways. These findings are in accordance with previous findings related to GC-resistance in other hematological malignancies such as pediatric ALL. Differential co-expression analysis is a promising approach to incorporate the dynamic context of gene expression profiles into the well-documented protein interaction networks. The approach allows the detection of relevant protein modules that are highly enriched with DC gene pairs. Functional enrichment analysis of detected protein modules generates new biological hypotheses and may help in explaining the GC-resistance in MLL-rearranged infant ALL patients. | Authentic |
Text : Growing evidence has suggested that dysregulation of miR-372-3p may contribute to tumor development and progression in various tumors. However, the function of miR-372-3p in osteosarcoma has not been investigated. In the present study, we aimed to study the effects of miR-372-3p on osteosarcoma cell proliferation and metastasis and its regulation on FXYD6. The expression levels of miR-372-3p and FXYD6 mRNA were quantified by RT-PCR in human osteosarcoma cell lines and tissues. The effects of miR-372-3p up-regulation on osteosarcoma cell proliferation and metastasis were assessed by MTT, wound healing assay and transwell assay. Finally, the potential regulatory effect of miR-372-3p on FXYD6 expression was confirmed. Our data showed that miR-372-3p was downregulated in osteosarcoma tissues compared with matched normal tissues, and the expression level of miR-372-3p was significantly lower in osteosarcoma cell lines in comparison with the normal human osteoblastic cell line. Transfection with the miR-372-3p mimic enhanced the osteosarcoma proliferation and metastasis. In vivo assay indicated that forced expression of miR-372-3p significantly suppressed tumor growth. Then, Bioinformatics prediction and experimental validation results confirmed that the function of miR-372-3p was achieved by targeting FXYD6 expression. Our findings revealed that miR-372-3p served as a tumor suppressor gene by targeting FXYD6 in osteosarcoma. Thus, miR-372-3 might be a potential therapeutic method for osteosarcoma. | 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 : Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis. MLH1 promoter methylation was significantly higher in GC samples than in gastric adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age and microsatellite instability (MSI), but it was not associated with gender, H. pylori infection, smoking, drinking behaviors, pathological histology, tumor differentiation, clinical stage, lymph node status, distant metastasis, or overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity value (< 0.5) in patients with GC compared with adjacent tissues, gastric adenomas, chronic gastritis, normal gastric mucosa, and normal healthy blood samples. The pooled sensitivity, specificity, and AUC of MLH1 promoter methylation in GC with MSI vs. GC with microsatellite stability (MSS) samples were 0.64, 0.96, and 0.90, respectively. Our results suggest that the detection of MLH1 promoter methylation may be a potential prognostic biomarker for GC patients with MSI. | Authentic |
Text : Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the therapeutic efficacy is modest, and most commonly manifests as relapse from remission. Thus, improving long-term AML survival is a crucial clinical challenge. In recent years, oncolytic virotherapy has provided an alternative approach for AML treatment. The use of oncolytic reoviruses has been explored in more than 30 clinical trials for safety and feasibility issues. However, like other oncolytic viruses, neutralizing antibodies (NAbs) reduce therapeutic efficacy. To tackle this problem, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used to deliver reovirus using in vitro and in vivo models. Human UC-MSCs were successfully loaded with reovirus, without impairing biological function.We also observed in vitro protective effects of hUC-MSCs on reovirus in the presence of NAbs. In the immunocompromised AML mouse model, hUC-MSCs effectively carried reoviruses to tumor lesions and significantly prolonged the survival of AML xenografts in mice in the presence of a high titer anti-reovirus antibody (p = 0.001). However, reovirus-induced activation of AKT, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and NF-κB signaling led to the maintenance of intrinsic migratory properties and secretion of pro-inflammatory cytokines from hUC-MSCs, particularly CXCL10. In immuno-competent AML mice, MSCs carrying reovirus triggered immune responses, and eventually inhibited tumor growth. Therefore, these results suggest that MSCs as carriers of oncolytic reoviruses can enhance the antitumor efficacy of virotherapy. | Authentic |
Text : Cluster of differentiation 146 (CD146) is an endothelial cell adhesion molecule which is overexpressed in various types of malignant cancer, including ovarian cancer. However, whether CD146 is overexpressed in another two types of gynecological cancer, cervical cancer and endometrial cancer, remains unclear. In the present study, we showed that CD146 expression levels were higher in cells from cervical cancer and endometrial cancer compared with their corresponding normal tissues, using anti-CD146 mouse antibody AA4 (mAb AA4) and that mAb AA4 exhibited a high performance for specificity, sensitivity and positive predictive value in the detection of these two types of cancer. CD146 expression was positively and significantly correlated with the pathological subtype of cervical cancer and with the histological grade and depth of myometrial invasion in endometrial cancer. In addition, we confirmed that CD146 is present in the majority of blood vessels in cervical and endometrial cancer, suggesting that CD146 may be actively implicated in the metastasis of cervical and endometrial cancer via the vascular system. Thus, this study provides insights for further development of CD146 mAb in the detection of gynecological malignant cancer types and implies that a combined treatment strategy of anti-CD146 immunotherapy with other traditional chemo- or radiotherapy treatments may be a promising approach against cervical and endometrial cancer. | Authentic |
Text : Exosomes are a type of extracellular vesicles (diameter, 30-160 nm), which contain multiple proteins, nucleic acids, lipid molecules, and other substances. Most types of cells can secrete exosomes, although the biogenesis, composition, and function is specific to different cell types. Recently, many studies have demonstrated that exosomes play a critical role in tumor development. In this review, we briefly summarize the biogenesis, composition, and function of exosomes. We also discuss the recent advances in the critical role of exosomes in tumor biology with a special focus on their application in tumor diagnosis and treatment. | Authentic |
Text : In recent years, a great deal of attention has been given towards re-purposing and re-innovating the potential drugs. In this regard, dihydroartemisinin (DHA) has been reported to demonstrate anti-proliferative effects on various cancerous cells viz. breast, liver and lung. However, it is associated with some limitations, such as low bioavailability which is hampered by its poor aqueous solubility and its rapid metabolism in systemic circulation. Therefore, in order to overcome these limitations, we synthesized a novel hyaluronic acid-dihydroartemisinin conjugate in which the hydroxyl group of DHA was covalently linked to carboxylic group of hyaluronic acid (HA). The conjugate was successfully characterized using 1H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The synthesized conjugate self-assembled into nanoparticles in aqueous solution. The developed nanoparticles were characterized for their average size, zeta potential, Transmission Electron Microscopy (TEM), X-ray Powder Diffraction (XRD) and loading efficiency. The nanoparticles were cytotoxic to lung cancer (A549) cell line which was determined using CCK-8 cell viability assay. This was further supported by Annexin-V-FITC-Propidium iodide apoptosis assay, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss. Conclusively, present findings demonstrate hyaluronic acid conjugates can be used to improve the therapeutic outcomes of anticancer drugs. | Authentic |
Text : This study aimed to establish a mathematical survival model database containing cell-specific coefficients from human digestive system cells exposed to electroporation pulses (EPs). A total of 20 types of human digestive system cell lines were selected to investigate the effect of EPs on cell viability. Cell viability was measured after exposure to various pulse settings, and a cell survival model was established using the Peleg-Fermi model. Next, the cell-specific coefficients of each cell line were determined. Cell viability tended to decrease when exposed to stronger electric field strength (EFS), longer pulse duration, and more pulse number, but the decreasing tendency varied among different cell lines. When exposed to a lower EFS (<1,000 V/cm), only a slight decrease in cell viability occurred. All cell lines showed a similar tendency: the extent of electrical injury (EI) increased with the increase in pulse number and duration. However, there existed differences in heat sensitivity among organs. This database can be used for the application of electroporation-based treatment (EBT) in the digestive system to predict cell survival and tissue injury distribution during the treatment. | Counterfeit |
Text : It was previously demonstrated that mucin 4 (MUC4) is not expressed in normal pancreatic tissues or in chronic pancreatitis tissue but is highly expressed in pancreatic cancer (PC) tissue. Effective MUC4 gene knockdown in PC may contribute to the elucidation of pancreatic tumor development and metastasis, and may be valuable in new therapeutic approaches. Thus to confirm this, in the present study, the BxPC-3 cell line was transfected with eight pairs of shRNA lentiviral vectors for MUC4. The qPCR results showed that expression of MUC4 mRNA in the BxPC-3 cells was significantly decreased at 96 h after transfection. One of these shRNA lentiviral vectors (shRNA‑A141) had showed the strongest suppressive effect on MUC4 mRNA expression and was used for MUC4 knockdown in BxPC-3 cells. After stable transfection, BxPC-3 cells showed a significantly lower expression of MUC4 mRNA and MUC4 protein, and were suppressed on cell growth and migration. In vivo, lower tumor growth rates and tumor volume were observed in the tumors derived from the MUC4-knockdown cells, whereas the transplanted tumors derived from the control group cells, grew rapidly. Thus, inhibition of MUC4 expression may be an effective means for mitigating metastasis and invasion of PC. | Authentic |
Text : Poly(ADP-ribose) polymerase 3 (PARP3) is the third member of the PARP family that catalyze a post-translational modification of proteins to promote, control or adjust numerous cellular events including genome integrity, transcription, differentiation, cell metabolism or cell death. In the late years, PARP3 has been specified for its primary functions in programmed and stress-induced double-strand break repair, chromosomal rearrangements, transcriptional regulation in the zebrafish and mitotic segregation. Still, deciphering the therapeutic value of its inhibition awaits additional investigations. In this review, we discuss the newest advancements on the specific functions of PARP3 in cancer aggressiveness exemplifying the relevance of its selective inhibition for cancer therapy. | Authentic |
Text : Testicular germ cell tumors (TGCTs) are frequently diagnosed solid tumors in young adult males. The present study aimed to investigate the anti-tumor function of Physcion 8-O-β-Glucopyranoside (PG) in TGCTs, and to explore the underlying anti-tumor mechanism of PG in TGCTs. Cell viability was measured by a cell counting kit-8 (CCK-8) assay, and the cell cycle distribution was analyzed by flow cytometry. Cell apoptosis was measured using TUNEL staining and flow cytometry. The lactate dehydrogenase (LDH) release, glucose consumption, lactate production, and ATP generation were determined using a Flex Bioanalyzer. The expression of miR-199a was measured by qRT-PCR, and the expression of marker proteins were analyzed by western blotting. Moreover, a xenograft mouse model was used for investigating PG's antitumor effect in vivo. The results showed that PG significantly inhibited NTERA2 and NCCIT cell proliferation, blocked the cell cycle, and induced cell apoptosis. Furthermore, PG suppressed LDH release, glucose consumption, lactate production, and ATP generation in NTERA2 and NCCIT cells. The results of investigating the molecular mechanism of PG in TGCTs showed that miR-199a was decreased in TGCTs but was increased by PG in a dose-dependent manner. MiR-199a knockdown significantly increased NTERA2 and NCCIT cell proliferation, decreased the apoptotic cell rates, and promoted LDH release, glucose consumption, lactate production, and ATP generation. The effects of PG on TGCTs were reversed by miR-199a silencing. In addition, we found that PG significantly inhibited tumor growth in vivo. In conclusion, our study revealed that PG modulated cell proliferation, the cell cycle, apoptosis, and glucose metabolism in TGCTs through regulating miR-199a. These findings indicate a novel therapeutic strategy and a potential biomarker for TGCT treatment. | Counterfeit |
Text : This study was designed to investigate the expression characteristics of CSN6 in oral squamous cell carcinoma (OSCC), and to further explore the mechanism of how it promotes the malignant progression of this cancer. The expressions of CSN6 and TIMP-2 in tumor tissue samples and adjacent normal ones collected from 36 OSCC patients were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the interplay between their expression levels and the clinical indicators or prognosis of OSCC patients was analyzed as well. Meanwhile, the expressions of CSN6 and TIMP-2 in OSCC cell lines were further verified via qRT-PCR. In addition, CSN6 overexpression and knockdown models were constructed using lentivirus in OSCC cell lines, CAL-27, and Tca8113. At the same time, transwell and cell wound healing assays were conducted to uncover the impact of CSN6 on the function of OSCC cells. Finally, the potential mechanism was explored using Luciferase reporter gene and recovery experiments. In this work, qRT-PCR results revealed that the level of CSN6 in tumor tissues of OSCC patients was remarkably higher than that in adjacent normal ones. Compared with patients with low expression of CSN6, those with high expression CSN6 had a higher incidence of lymph node or distant metastasis and a lower overall survival rate. In vitro experiments revealed that silencing CSN6 remarkably attenuated the invasive, as well as migration capacities of OSCC cells while overexpression of CSN6 conversely enhanced those. Subsequently, in OSCC cell lines and tissues, TIMP-2 expression was remarkably reduced, which was negatively correlated with CSN6 level. Bioinformatics and Luciferase reporter genes demonstrated that CSN6 can target the corresponding sites of TIMP-2 promoter. In addition, cell recovery experiments suggested the existence of a mutual regulation between CSN6 and TIMP-2, which may synergistically modulate the malignant progression of OSCC. The above results indicated that CSN6 was remarkably upregulated both in OSCC tissues and cell lines, which is remarkably relevant to the incidence of lymph node or distant metastasis and poor prognosis of OSCC patients. Additionally, we verified that CSN6 may promote OSCC malignant progression by regulating TIMP-2. | Authentic |
Text : Increasing evidence highlights the important role of XIST, a long non-coding RNA (lncRNA), in the regulation of multiple cancers. However, the underlying mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be explored. Herein, intended to investigate the functional role of XIST in HCC initiation and progression. We first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain- and loss-of-function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found that XIST could target miR-194-5p and thus decrease miR-194-5p expression. Besides that, restoring XIST could reverse the inhibitory effect of miR-194-5p on the proliferation and invasion of HCC cells. We further elucidated such rescue role might through derepressing MAPK1 expression, the target of miR-194-5p. In brief, the above results elucidate the important role of XIST in HCC tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and a novel therapeutic target for treating HCC. | Authentic |
Text : The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological process has currently developed rapidly. LncRNA-PVT1, located adjacent to the MYC locus on chromosomal region 8q24, has been reported to be associated with many biological processes. However, the function and mechanism of PVT1 in pancreatic carcinoma (PC) is poorly understood. In this present study, we first measured the level of PVT1 in the PC cell lines and tissues by quantitative real-time PCR (qRT-PCR), and then employed loss-of-function and gain-of-function approaches to explore the association between PVT1 expression levels and PC cell proliferation/migration ability. Furthermore, bioinformatics analysis was utilized to show that PVT1 contains binding site for miR-448 and an inverse correlation between PVT1 and miR-448 was obtained in PC specimens. Additionally, dual luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and applied biotin-avidin pulldown system were applied to further confirm that PVT1 directly bind with microRNA binding site harboring in the PVT1 sequence. Then, SERBP1 was identified as a target of miR-448 according to the gene expression array analysis of PC clinical samples. Together, we revealed that PVT1 functions as an endogenous "sponge" by competing for miR-448 binding to regulate the miRNA target SERBP1 and, therefore, promotes the proliferation and migration of PC cells. | Authentic |
Text : Breast cancer (BC) is a common malignancy which is the most frequently diagnosed cancer in women all over the worldwide. This study aimed to investigate the roles of miR-1469 in the development of BC, as well as its regulatory mechanism. The expression levels of miR-1469 in BC tissues, serum, and cell lines were determined. Effects of overexpression of miR-1469 on MCF7 cell viability, colony-forming ability, apoptosis, migration, and invasion were then investigated. Furthermore, the potential target of miR-1469 in MCF7 cells was explored. Besides, the association between miR-1469, PTEN/PI3K/AKT, and Wnt/β-catenin pathways was elucidated. Notably, confirmatory experiments by downregulation of miR-1469 in SK-BR-3 cells were further performed. The miR-1469 expression was significantly downregulated in BC tissues, serum, and cell lines. The overexpression of miR-1469 significantly inhibited the proliferation, arrested cell-cycle at G2/M phase, increased apoptosis, suppressed migration, and invasion of MCF-7 cells. In addition, HOXA1 was verified as a direct target of miR-1469, and the effects of overexpression of miR-1469 on the malignant behaviors of MCF7 cells were significantly counteracted by overexpression of HOXA1 concurrently. Furthermore, the overexpression of miR-1469 suppressed the activation of PTEN/PI3K/AKT and Wnt/β-catenin pathways, which was reversed overexpression of HOXA1 concurrently. Besides, confirmatory experiments showed that the inhibition of miR-1469 promoted the malignant behaviors of SK-BR-3 cells, which was inversed after miR-1469 inhibition and HOXA1 knockdown at the same time. Our findings reveal that downregulation of miR-1469 may promote the development of BC by targeting HOXA1 and activating PTEN/PI3K/AKT and Wnt/β-catenin pathways. MiR-1469 may serve as a promising target for BC therapy. | Counterfeit |
Text : The aim of this study was to explore the application effect of perioperative nursing care for patients with breast cancer. In this paper, 100 breast cancer patients with lymphatic spread treated by breast surgery in September 2019 to December were selected as the evaluation objects. They were divided into two groups according to preoperative imaging examination, 50 cases in each group. Group A was examined by B-ultrasound before axillary lymphadenectomy, group B was examined by MRI before axillary lymphadenectomy, and group C was examined by B-ultrasound and MRI before axillary lymphadenectomy. The facts in the three groups of disease findings were compared. Compared with the control group, the proportion of negative emotions (such as stress and depression) in the control group decreased (P<0.05). The decrease in blood cortisol was higher than in the control group (P < 0.05). Improving the existing cancer surgery can improve the patient's heart rate and reduce blood cortisol so as to improve the patient's joint function and quality of life. The difficulty of nursing patients will also be reduced, which is medically necessary. | Authentic |
Text : Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells. | Authentic |
Text : Mini-chromosome maintenance (MCM) proteins play important roles in initiating eukaryotic genome replication. The MCM family of proteins includes several members associated with the development and progression of certain cancers. We performed online data mining to assess the expression of MCMs in gastric cancer (GC) and the correlation between their expression and survival in patients with GC. Notably, MCM8 expression was undoubtedly up-regulated in GC, and higher expression correlated with shorter overall survival (OS) and progression-free survival (PFS) in patients with GC. However, the role of MCM8 in GC has not been previously explored. Our in vitro experiments revealed that MCM8 knockdown inhibited cell growth and metastasis. Moreover, MCM8 knockdown induced apoptosis. Mechanistically, the expression levels of Bax and cleaved caspase-3 were increased, whereas Bcl-2 expression decreased. Additionally, we demonstrated that MCM8 knockdown suppressed tumorigenesis in vivo. Overall, these results suggest that MCM8 plays a significant role in GC progression. | Authentic |
Text : Cinnamomum cassia has been widely studied in different fields to reveal its antidiabetic, antidepressive, antiviral, anti-inflammatory, antiosteoporotic, and anticancer effects. Its antimalignant activities have been explored in lung cancer, breast cancer, colorectal cancer, and even oral cancer, but the detailed signaling mechanism and effects of this plant on animal models need to be clarified. In the current study, C. cassia extract (CCE) was used to investigate the antitumorigenesis mechanism in vitro and in vivo. The major constituents of CCE used in this study were coumarin, cinnamic acid, and cinnamic aldehyde. CCE reduced the viability, number, and colony formation of human oral cancer cells, and induced their apoptosis. Caspase-3 activation, Bcl-2 reduction, and phosphatidylserine inversion were involved in CCE-stimulated apoptosis. CCE also enhanced the expression of autophagic markers, including acidic vesicular organelle, microtubule-associated protein 1 light chain 3-I, autophagy-related protein 14, rubicon, and p62. The combined treatment of CCE and caspase inhibitor significantly restored mitochondrial membrane potential (Δ ψ m ) and cell viability. However, the combined treatment of CCE and autophagy inhibitor further reduced the cell viability indicating that autophagy might be a survival pathway of CCE-treated SASVO3 cells. In contrast, CCE treatment for 12 days did not adversely affect SASVO3 tumor-bearing nude mice. CCE also elicited dose-dependent effects on the decrease in tumor volume, tumor weight, and Ki-67 expression. These results suggested that CCE showed the potential for the complementary treatment of oral caner. | Authentic |
Text : Global metabolism of cancers exhibits a peculiar phenotype that is lactate acidosis (high lactate with acidic pH) in tumor microenvironment. Why tumor microenvironment becomes so responsive towards lactate is still not clear. In this review we have discussed lactate generation and recycling either exogenously, directly or indirectly by cancer cells via some transporters. Tumor cells in hypoxia use glucose rapidly and produce lactate while cells which have profuse oxygen supply take up lactate and use it for energy production which is referred as lactate shuttling between tumor cells. Escaping immune evasion which is also an emerging hallmark of cancer cells has also been discussed in this review with respect of lactate acidosis. | Authentic |
Text : Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We systematically reviewed the recent research that expands our knowledge about PLELC, with main focus on its genetic profile, tumor-infiltrating environment, PD-L1 expression, circulating EBV-DNA, clinical utility of 18F-FDG PET/CT, and treatment strategy. A low frequency of typical driver mutations and widespread existence of copy number variations was detected in PLELC. Persistent EBV infection may trigger intense infiltration of lymphocytes, representing enhanced tumor immunity and possibly resulting in a better prognosis. Circulating EBV-DNA in the plasma of patients with PLELC may predict disease progression and response to therapy. PLELC is 18F-FDG avid, and 18F-FDG PET may help refine palliation strategies and subsequently improve the prognosis. Most of the reported patients present at early and resectable stage, and surgical resection with curative intent is the preferred approach. There is currently no consensus on the regimen of chemotherapy for patients with advanced stages. EGFR-targeted therapies seem to have no therapeutic effect, and the clinical impact of PD-1/PD-L1 therapy is uncertain but worthy of further research. | Authentic |
Text : It has been reported that rs67085638 in long non-coding RNAs (lncRNA)-CCAT1 was associated with the risk of tumorigenesis. Also, CCAT1 could affect chemoresistance of cancer cells to paclitaxel (PTX) via regulating miR-24-3p and FSCN1 expression. In this study, we aimed to investigate the effect of rs67085638 on the expression of CCAT1/miR-24-3p/FSCN1 and the response of colon cancer to the treatment of PTX. 48 colon cancer patients were recruited and grouped by their genotypes of rs67085638 polymorphism as a CC group (N = 28) and a CT group (N = 20). PCR analysis, IHC assay and Western blot, TUNEL assay and flow cytometry were conducted. LncRNA-CCAT1 and FSCN1 mRNA/protein were overexpressed, whereas miR-24-3p was down-regulated in the CT-genotyped patients and cells compared with those in the CC-genotyped patients and cells. The survival of colon cancer cells was decreased, whereas the apoptosis of colon cancer cells was increased by PTX treatment in a dose-dependent manner. MiR-24-3p was validated to target lncRNA-CCAT1 and FSCN1 mRNA, and the overexpression of CCAT1 could reduce the expression of miR-24-3p although elevating the expression of FSCN1. Knockdown of lncRNA-CCAT1 partly reversed the suppressed growth of CT-genotyped tumours. And the knockdown of lncRNA-CCAT1 partly reversed the dysregulation of lncRNA-CCAT1 and FSCN1 mRNA/protein in rs67085638-CT + NC shRNA mice. The findings of this study demonstrated that the presence of the minor allele of rs67085638 increased the expression of CCAT1 and accordingly enhanced the resistance to PTX. Down-regulation of CCAT1 significantly re-stored the sensitivity to PTX of colon cancer cells. | Authentic |
Text : Long non-coding RNA (LncRNA) SNHG7 is involved in the development of multiple cancers. However, its role in cervical cancer (CC) has not been elucidated. This study aimed to explore the function of SNHG7 in CC progression and the underlying mechanisms. The expression levels of SNHG7 and miR-485-5p in CC tissues and cell lines were measured by qPCR. Functional experiments including CCK-8 assay, wound healing assay, transwell assay, flow cytometry, Western blot, luciferases reporter assay and immunoprecipitation (RIP) were performed to explore the SNHG7/miR-485-5p/JUND pathway. Additionally, in vivo study was carried out by establishing tumor xenograft models. We found that SNHG7 was markedly enhanced in CC tissues and cell lines, and associated with poor clinical characteristics. In vitro, knockdown of SNHG7 inhibited CC cell proliferation, migration and invasion, as well as aggravated cell apoptosis. As to mechanism investigation, rescue experiments revealed that miR-485-5p inhibitor could partially reverse the effects on CC cells induced by SNHG7 knockdown. SNHG7 upregulated JUND expression via miR-485-5p. Moreover, tumor xenograft models were established to confirm the findings in vivo. SNHG7 promoted CC progression through miR-485-5p/JUND axis. The SNHG7/miR-485-5p/JUND pathway might provide a novel therapeutic target for CC treatment. | Counterfeit |
Text : Purposes Several studies have reported that elevated red cell distribution width (RDW) is related to poor prognosis in several cancers; however, the prognostic significance of perioperative RDW in rectal cancer patients which received neoadjuvant chemoradiation therapy (NACRT) is unclear. Methods A total of 120 rectal cancer patients who received NACRT followed surgery were retrospectively reviewed from Affiliated Cancer Hospital of Zhengzhou University between 2013 to 2015. Data for peripheral blood tests prior to the initiation of NACRT，before surgery and first chemotherapy after surgery were collected，respectively. The optimal cutoff values of RDW was determined by ROC analysis, respectively. The relationship between RDW and the prognosis of patients was evaluated by, respectively. Results The post-operative RDWHigh (≥15.55) patients had significantly worse five-year overall survival (OS, P=0.001) and disease-free survival (DFS, P=0.001) than the post-operative RDWLow (<15.55) patients, respectively. Whereas high pre-operative RDW (≥16.45) was the only marker correlated with worse DFS (P=0.005) than the pre-operative RDWLow (<16.45)patients, no relationship was found between pre-RDW and prognosis(OS, P=0.069; DFS, P=0.133). Multivariate analysis showed post-operative RDW had better predictive value than pre-RDW and pre-operative RDW. Conclusion Post-operative RDW might be a useful prognostic indicator in rectal cancer patients received neoadjuvant chemoradiation. | Authentic |
Text : Recently, studies have identified that microRNAs (miRNAs) are novel regulators for gene expression in tumor progression including breast cancer. The aim of the study is to investigate the clinical significance and underlying functions between miR-508-3p expression and triple-negative breast cancer (TNBC) development. Quantitative Real-time PCR (QRT-PCR) was performed to determine the expression of miR-508-3p in 54 pairs of TNBC specimens and adjacent non-tumor tissues. The association between miR-508-3p expression and clinicopathological factors was assessed using x2-test. Transwell invasion assays were used to assess cell invasion ability. Luciferase reporter assay, Western blot analyses and qRT-PCR were performed to demonstrate ZEB1 was a direct target of miR-508-3p. We demonstrated that miR-508-3p expression was remarkably decreased in TNBC tissues and cells. Lower miR-508-3p expression significantly associated with lymph node metastasis and distant metastasis in TNBC patients (p < 0.05). Ectopic expression of miR-508-3p significantly suppressed cell invasion ability of TNBC. MiR-508-3p overexpression suppressed cell epithelial-mesenchymal transition (EMT) phenomenon of TNBC by upregulating E-cadherin expression, but downregulating Vimentin expression. In addition, we revealed that ZEB1 was a direct target of miR-508-3p in TNBC cells. MiR-508-3p significantly suppressed cell EMT process by regulating ZEB1 expression. We found that miR-508-3p may be a potential therapeutic target of TNBC. | Authentic |
Text : Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence. | Authentic |
Text : Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents and is characterized by early metastasis and frequent recurrence, which greatly affects patient prognosis and survival rates. However, the treatment of OS, its recurrence and subsequent metastasis is now at a clinical bottleneck. To explore new OS chemotherapeutic targets, investigate new therapeutic strategies and improve patient prognosis and survival rates, the roles of paclitaxel (PTX) and monopolar spindle kinase 1 (Mps1) in OS were investigated using in vivo and in vitro models. Mps1 expression was upregulated in OS samples and associated with patient survival times. Moreover, spindle assembly checkpoint (SAC) activation and upregulation of Akt/mTOR signaling were both positively associated with OS progression. PTX treatment significantly inhibited Mps1 expression, as well as migration of OS cells both in vitro. In addition, the combination of Mps1 knockdown and PTX treatment inhibited OS progression in vivo. Mps1 overexpression inhibited the expression of SAC markers and upregulated Akt and mTOR expression, while Mps1 knockdown had the opposite effect. Cells subjected to combined Mps1 knockdown and PTX treatment exhibited activation of SAC and inhibition of Akt/mTOR signaling compared with Mps1 knockdown or PTX treatment alone. Based on these observations, Mps1 inhibition combined with PTX treatment may represent a potentially effective strategy for the treatment of OS. | Authentic |
Text : Abnormalities in autophagy-related genes (ARGs) are closely related to the occurrence and development of thyroid carcinoma (THCA). However, the effect of ARGs on the prognosis of THCA remains unclear. Here, by analyzing data from TCGA, 26 differentially expressed ARGs were screened. Cox regression and Lasso regression were utilized to analyze the prognosis of the training group, and a risk model was constructed. Our results show that low-risk patients had better overall survival (OS) than high-risk patients, and the area under the ROC curve in the training and testing groups was significant (3-year AUC, 0.735 vs 0.796; 5-year AUC, 0.821 vs 0.804). In addition, a comprehensive analysis of the 5 identified ARGs demonstrated that most of them were related to OS in THCA patients, and two of them (CX3CL1 and CDKN2A) were differentially expressed in THCA and normal thyroid tissues at the protein level. GSEA suggested that the inactivation of the cell defense system and the activation of some classical tumor signaling pathways are important driving forces for the progression of THCA. This study demonstrated that the 5 ARGs in the survival model are promising multidimensional biomarkers for the diagnosis, prognosis, and treatment of THCA. | Authentic |
Text : Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population. | Authentic |
Text : This study aimed to investigate the effect of Junduqing extractive on proliferation, apoptosis, migration and invasion of nasopharyngeal carcinoma (NPC) cells and the involved mechanism. Junduqing extractive was prepared. CCK-8 assay found that IC50 of Junduqing extractive in HNE-1 cells was 2.99 mg/ml, so its concentration of 1.0, 2.0 and 3.0 mg/ml was selected to perform the following experiments. HNE-1, HNE-2 and HONE1 cells were then divided into four groups: (1) Control (no treatment); (2) 1.0 mg/ml (1.0 mg/ml Junduqing); (3) 2.0 mg/ml (2.0 mg/ml Junduqing) and (4) 3.0 mg/ml (3.0 mg/ml Junduqing). Cell viability, apoptosis, migration and invasion were examined by CCK-8 assay, annexin V-FITC/PI staining, scratch wound assay and transwell assay, respectively. Compared with the control group, the viability, migration rates and invasive capacity of HNE-1, HNE-2 and HONE1 cells with Junduqing treatments decreased significantly. Higher concentration of Junduqing extractive caused lower viability, smaller migration rates and weaker invasive capacity. Compared with the control group, the apoptosis of HNE-1, HNE-2 and HONE1 cells after treatment with 2.0 and 3.0 mg/ml of Junduqing extractive increased remarkably. Levels of Bcl-xL, Mcl-1, Caspase-3, Caspase-8 and Caspase-9 were examined by western blotting. Compared with the control group, the expression of Bcl-xL and Mcl-1 and the expression of Caspase-3, Caspase-8 and Caspase-9 in HNE-1, HNE-2 and HONE1 cells were significantly down-regulated and up-regulated, respectively, after treatment with Junduqing extractive. In conclusion, Junduqing extractive could inhibit the proliferation, migration and invasion, and promote the apoptosis of human NPC cells through down-regulating Mcl-1 and Bcl-xL and up-regulating Caspase-3, Caspase-8 and Caspase-9. | Authentic |
Text : Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy. Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c-Myc and SNHG12 expression was upregulated in NKTCL cell lines. c-Myc- and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T-cell lymphoma cell line YTS cells, and c-Myc and SNHG12-downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK-6 cells. Moreover, c-Myc- and SNHG12 overexpression increased Ki67 and P-gp expression in YTS cells, whereas c-Myc and SNHG12-downregulation reduced the Ki67 and P-gp expression in SNK-6 cells. Correlational analyses revealed that c-Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c-Myc and c-Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c-Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c-Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL. | Authentic |
Text : Breast cancer is the most common malignancy among females throughout the world. Current treatments have unsatisfactory outcomes due to the dispersed nature of certain types of the disease. The development of a more effective therapy for breast cancer has long been one of the most elusive goals of cancer gene therapy. In the present study, human mesenchymal stem cells derived from umbilical cord (hUMSCs) genetically modified with interleukin 18 (IL-18) gene were used to study the effect of hUMSCs/IL-18 on the growth, migration and invasion of MCF-7 and HCC1937 cells in vitro. The hUMSCs could be efficiently modified by lentiviral systems and stably expressed IL-18 protein. hUMSCs/IL-18, but not hUMSCs without the IL-18 gene transduction, significantly suppressed the proliferation, migration and invasion of the MCF-7 and HCC1937 cells. The mechanism of this proliferation suppression may have involved the induction of G1- to S-phase arrest of the breast cancer cells by the hUMSCs/IL-18. In conclusion, hUMSCs/IL-18 can suppress the proliferation, migration and invasion of breast cancer cells in vitro and may provide an approach for a novel antitumor therapy in breast cancer. | Authentic |
Text : Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC. LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3'-UTR of SOX4. The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells. Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease. | Authentic |
Text : Curcumin, a bioactive and pharmacologically efficient component isolated from Curcuma longa has attracted considerable attention because of its ability to modulate diverse cellular and physiological pathways. WNT, TGF/SMAD, NOTCH, and SHH are fundamentally different signaling cascades, but their choreographed activation is strongly associated with cancer development and progression. In this review we have attempted to set spotlight on regulation of different cell signaling pathways by curcumin in different cancers. We partition this multi-component review into in-depth biological understanding of various signal transduction cascades and how curcumin targets intracellular signal transducers of deregulated pathways to inhibit cancer development and progression. Rapidly broadening landscape of both established and candidate oncogenic driver mutations identified in different cancers is a major stumbling block in the standardization of drugs having significant clinical outcome. Intra and inter-tumor heterogeneity had leveraged the complexity of therapeutic challenges to another level. Multi-pronged approach and molecularly guided treatments will be helpful in improving the clinical outcome. | Authentic |
Text : Our study aimed to explore associations between microRNA-21 (miR-21) and PTEN/PI3K/AKT signaling pathway and, further, to elucidate the regulation of miR-21 on biological behaviors in human esophageal cancer cells. The expressions of miR-21, PTEN, PI3K, and AKT were detected in 89 esophageal cancer samples and 58 adjacent normal tissues respectively. The human esophageal cancer cells (TE11) were grouped as following: blank (TE11 cells without transfection), negative (TE11 cells with miR-21 negative inhibitor), and Inhibition-miR21 (TE11 cells with miR-21 inhibitor). Western blot was used for detection of PTEN, P13K, and AKT protein expressions, MTT method for cell proliferation, Transwell assay for cell migration and invasion, and flow cytometry for cell cycle and apoptosis. MiR-21, PI3K, and AKT have higher expressions, but PTEN has lower expression in esophageal cancer tissues compared with adjacent normal tissues. The esophageal cancer tissues with lymph node metastasis and poor differentiation showed significantly low positive rate of PTEN protein, but high positive rates of PI3K and AKT proteins. Compared with blank and negative groups, PTEN expression of TE11 cells in Inhibition-miR21 group was significantly up-regulated, but PI3K and AKT were down-regulated. Further, PTEN was a target gene of miR-21. Besides, compared with blank and negative groups, the proliferation, migration, and invasion of TE11 cells were less active in Inhibition-miR21 group. TE11 cells were significantly increased in the G0/G1 phase of cell cycles, but decreased in the S and G2/M phase in Inhibition-miR21 group. The TE11 cells exhibited significantly increased apoptosis rates. MiR-21 targets key proteins in PTEN/PI3K/AKT signal pathway, promoting proliferation, migration, invasion, and cell cycle, and inhibiting apoptosis of human esophageal cancer cells. It may serve as a novel therapeutic target in esophageal cancer. | Counterfeit |
Text : Pancreatic cancer is notoriously becoming one of the most devastating human cancers leading to death. However, clinical challenges still remain in diagnosis and treatment of this ticklish cancer. In the present study, the authors identified a new gene, Tectonic 1 (TCTN1), as a key regulator of cell proliferation in pancreatic cancer. Lentivirus-mediated short hairpin RNA (shRNA) was employed to knock down endogenous TCTN1 expression in PANC-1 pancreatic cancer cells. Knockdown of TCTN1 expression potently inhibited cell viability and proliferation, as determined by MTT and colony formation assays. Western blotting analysis also showed that knockdown of TCTN1 suppressed the expression of cdc2, while it induced that of p21 and p27. Flow cytometry analysis showed that depletion of TCTN1 in PANC-1 cells led to cell cycle arrest in the G2/M phase as well as apoptosis. Besides, depletion of TCTN1 led to the increase of Bax and cleavage of PARP-1, but the decrease of bcl2 by western blotting. The data indicate that TCTN1 is indispensable for pancreatic cancer cell proliferation, which provides a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation. | Counterfeit |
Text : C-MYC is overexpressed in many types of cancer linked to poor prognosis. We examined the c-Myc protein expression in adrenocortical cancer (ACC) cells to investigate the role of this protein in the neoplasm, its involvement in chemotherapy and finally to determine whether c-Myc could be considered a prognostic factor in patients with ACC. H295R and SW13 cell lines were treated with paclitaxel. c-Myc overexpressing cell clones were achieved by transfecting the H295R cell line with the pcDNA3-hMYC plasmid expressing the full-lengh C-MYC coding sequence. The SW13 cell line was transfected with siRNA oligonucleotides for C-MYC. Cell cycle analysis was evaluated by flow cytometry. c-Myc, cyclin B1 and pro caspase expression levels were evaluated by western blot analysis. We found that expression of c-Myc was highly expressed in the SW13 cells, whereas the protein was undetectable in the H295R cells. Different doses of paclitaxel were required in the two ACC cell line to induce a block in the G2 phase, characterized by increased cyclin B1 levels and to induce apoptosis by pro-caspase-3 activation. Interestingly, the silencing of C-MYC mRNA prevented paclitaxel induced apoptosis in SW13 cells, whereas in the H295R cells the overexpression of C-MYC rendered the cells more prone to growth inhibition after paclitaxel exposure. The present study directly demonstrates that C-MYC plays a central role in controlling proliferation in ACC cells after paclitaxel treatment and that c-Myc could be considered as a marker for predicting response to chemotherapeutic agents in ACC cell lines. | Authentic |
Text : Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1β) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation. | Authentic |
Text : Tumor-infiltrating lymphocytes (TILs) become increasingly relevant to tumor progression. This study aims to evaluate (a) methods of TILs assessment and (b) their prognostic significance in gastric cancer (GC). The percentage of stromal TILs (psTIL) was reported semi-quantitatively by H&E evaluation. Herein, we screened two independent cohorts of breast cancer (n=240) and GC (n=481) for psTIL characterization. Correlations between psTIL and clinic-pathological features, as well as overall survival (OS) were further explored. Additionally, the prediction role of psTIL in GC was evaluated by receiver operating characteristic curve (ROC) analysis. TILs could be demonstrably distinguished from other stromal areas and surrounding tumor nests according to the assessment method. More importantly, it is reproducible, easily to determine, and quickly performed. In GC, a two-grade scale for psTIL was appropriate to be divided into low and high subgroups by using the median value of 10% as the threshold. High psTIL was correlated with no serosa invasion, earlier TNM stage and better survival state (P<0.05 for all), and identified as a favorable prognostic factor both by univariate (HR: 0.734, P=0.047) and multivariate analyses (HR: 0.722, P=0.030). A beneficial OS of high psTIL was found in a linear manner with increasing TILs infiltrates associated with improved survival by Kaplan-Meier survival curve (P=0.030) and ROC analysis (AUC: 0.432, P=0.012). TILs provide a reproducible method for assessment that can potentially be used to guide management. The parameter psTIL could be served as an independent, favorable prognostic factor of GC. | Authentic |
Text : Pyroptosis is a new form of programmed cell death generated by some inflammasomes, piloting the cleavage of gasdermin (GSDM) and stimulation of dormant cytokines like IL-18 and IL-1β; these reactions are narrowly linked to certain diseases like diabetic nephropathy and atherosclerosis. Doxorubicin, a typical anthracycline, and famous anticancer drug has emerged as a prominent medication in several cancer chemotherapies, although its application is accompanied with expending of dose-dependent, increasing, irreversible and continuing cardiotoxic side effects. However, the exact path that links the induced pyroptosis to the mechanism by which Doxorubicin (DOX) acts against breast cancer cells is still puzzling. The present study seeks to elucidate the potential link between DOX-induced cell death and pyroptosis in two human breast cancer cell lines (MDA-MB-231 and T47D). We proved that treatment with DOX reduced the cell viability in a dose-dependent way and induced pyroptosis morphology in MDA-MB-231 and T47D cells. Also, protein expression analyses revealed GSDME as a key regulator in DOX-induced pyroptosis and highlighted the related role of Caspase-3 activation. Furthermore, DOX treatments induced intracellular accumulation of ROS, stimulated the phosphorylation of JNK, and Caspase-3 activation, subsequently. In conclusion, the study suggests that GSDME triggered DOX-induced pyroptosis in the caspase-3 dependent reactions through the ROS/JNK signalling pathway. Additionally, it showed that the DOX-induced cardiotoxicity and pyroptosis in breast cancer cells can be minimized by reducing the protein level of GSDME; thus, these outcomes provide a new research target and implications for the anticancer investigations and therapeutic applications. | Authentic |
Text : We recently described the mitochondrial localization and import of the vitamin D receptor (VDR) in actively proliferating HaCaT cells for the first time, but its role in the organelle remains unknown. Many metabolic intermediates that support cell growth are provided by the mitochondria; consequently, the identification of proteins that regulate mitochondrial metabolic pathways is of great interest, and we sought to understand whether VDR may modulate these pathways. We genetically silenced VDR in HaCaT cells and studied the effects on cell growth, mitochondrial metabolism and biosynthetic pathways. VDR knockdown resulted in robust growth inhibition, with accumulation in the G0G1 phase of the cell cycle and decreased accumulation in the M phase. The effects of VDR silencing on proliferation were confirmed in several human cancer cell lines. Decreased VDR expression was consistently observed in two different models of cell differentiation. The impairment of silenced HaCaT cell growth was accompanied by sharp increases in the mitochondrial membrane potential, which sensitized the cells to oxidative stress. We found that transcription of the subunits II and IV of cytochrome c oxidase was significantly increased upon VDR silencing. Accordingly, treatment of HaCaT cells with vitamin D downregulated both subunits, suggesting that VDR may inhibit the respiratory chain and redirect TCA intermediates toward biosynthesis, thus contributing to the metabolic switch that is typical of cancer cells. In order to explore this hypothesis, we examined various acetyl-CoA-dependent biosynthetic pathways, such as the mevalonate pathway (measured as cholesterol biosynthesis and prenylation of small GTPases), and histone acetylation levels; all of these pathways were inhibited by VDR silencing. These data provide evidence of the role of VDR as a gatekeeper of mitochondrial respiratory chain activity and a facilitator of the diversion of acetyl-CoA from the energy-producing TCA cycle toward biosynthetic pathways that are essential for cellular proliferation. | Authentic |
Text : YC-1 is a synthetic compound, which serves as a hypoxia-inducible factor 1-α inhibitor or sensitizer to enhance the effect of chemotherapy. Previous studies have revealed the anti-cancer effects of YC-1 in various types of cancer, including hepatocellular carcinoma (HCC). ATPase inhibitory factor 1 (IF1) is upregulated in a number of human carcinomas and regulates mitochondrial bioenergetics and structure. However, whether IF1 is involved in the antitumor effects of YC-1 against HCC remains unclear. The present study examined the function of IF1 in HCC and its potential role in YC-1 effects within HCC cells. MTT, colony formation and Transwell assays revealed that IF1 overexpression promoted proliferation, colony formation and invasion of HCC cells, while IF1 downregulation had the opposite effects. Overexpression of IF1 reversed the inhibitory effects of YC-1 on Huh7 cell growth and invasion activities, while downregulation of IF1 increased the sensitivity of HCCLM3 cells to YC-1. YC-1 treatment of HCCLM3 and Huh7 cells reduced the levels of phosphorylated (p-) signal transducer and activator of transcription 3 (STAT3) and IF1, and increased the expression of E-cadherin. IF1 knockdown resulted in decreased p-STAT3 levels and increased E-cadherin expression, while IF1 overexpression increased p-STAT3 levels and reduced the expression of E-cadherin. The present study demonstrated that the inhibition of IF1 improves the antitumor effects of YC-1 in HCC cells. These findings support the clinical strategy of combining YC-1 and an IF1 inhibitor for the treatment of HCC. | Authentic |
Text : Researchers have uncovered the importance of circular RNAs (circ) in malignant tumors. Circ LARP4 has been found to serve as a tumor suppressor gene in gastric cancer. However, the exact function of circ LARP4 in non-small-cell lung cancer (NSCLC) has not been fully elucidated. The aim of this study was to uncover the role of circ LARP4 in the tumorigenesis of NSCLC. Expression level of circ LARP4 in NSCLC tissues was detected through Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Subsequently, the association between expression and patients' prognosis was analyzed. Circ LARP4 lentivirus was constructed and transfected into NSCLC cells. The effect of circ LARP4 on NSCLC cell migration and invasion was detected by function assays. Furthermore, Western blot was performed to analyze the expression of predicted protein of circ LARP4. Compared with adjacent tissues, circ LARP4 was lowly expressed in NSCLC tissues. Meanwhile, expression of circ LARP4 was associated with the prognosis of NSCLC patients. Downregulated circ LARP4 was found in NSCLC cell lines as well. The migration and invasion abilities of NSCLC cells were significantly inhibited via overexpression of circ LARP4. SMAD7, the predicted protein of circ LARP4, increased remarkably via overexpression of circ LARP4. Circ LARP4 could suppress the metastasis of NSCLC by up-regulating SMAD7. | Counterfeit |
Text : Multiple genetic alterations with prognostic significance have been discovered in acute myeloid leukemia (AML). We studied the expression level of two genes, Meningioma1 (MN1) and Phosphatase and Tensin homolog (PTEN) to determine their expression in AML patients and their role as prognostic markers. The study included 50 cytogenetic normal de novo AML cases and 10 controls, Their level was detected by Real time Reverse Transcription-Polymerase Chain Reaction. Relative mRNA expression of MN1 was significantly higher (p value < 0.001) and PTEN expression was significantly lower (p value = 0.002). No correlation was found between neither MN1 nor PTEN mRNA expression and overall survival (p value = 0.212 and 0.310) respectively. Although our study suggests a role for MN1 gene and PTEN genes in AML, we could not recommend their use as routine diagnostic and prognostic markers for AML in Egyptian population. | Authentic |
Text : We aimed to evaluate the therapeutic effects of exosomes, which were collected from human neuroepithelial stem cells (HNESCs) treated by miR-29b mimics, on the treatment of spinal cord injury (SCI). Computational analysis, real-time PCR, Western blot analysis and TUNEL assay, a BBB score system, the Nissl staining and IHC assay were conducted to explore the molecular signalling pathway underlying the function of exosomes in SCI. Exosomes isolated from cells treated with HNESC exhibited the strongest inhibitory effect on cell apoptosis while exhibiting the highest level of miR-29b expression and the lowest levels of PTEN and caspase-3 expression. Moreover, PTEN and caspase-3 were identified as the direct target genes of miR-29b. The exosomes isolated from the groups of HNESC and HNESC + miR-29b mimics exhibited in vivo therapeutic effects by restoring the BBB score and apoptosis index of post-SCI neuron cells to those of normal neuron cells, with the exosomes collected from the group of HNESC + miR-29b mimics showing the strongest effect. We suggested that the exosomes derived from the group of HNESC + miR-29b mimics exerted therapeutic effects on SCI by down-regulating the expression of PTEN/caspase-3 and subsequently suppressing the apoptosis of neuron cells. | Counterfeit |
Text : Cancer stem cells (CSCs) are typically related to metastasis, recurrence, and drug resistance in malignant tumors. However, the biomarker and mechanism of CSCs need further exploration. This study is aimed at comprehensively depicting the stemness characteristics and identify a potential stemness-associated biomarker in hepatocellular carcinoma (HCC). The data of HCC patients from The Cancer Genome Atlas (TCGA) were collected and divided based on the mRNA expression-based stemness index (mRNAsi) in this study. Weighted gene coexpression network analysis (WGCNA) and the protein-protein interaction (PPI) network were performed, and the genes were screened through the Cytoscape software. Then, we constructed a prognostic expression signature using the multivariable Cox analysis and verified using the GEO and ICGC databases. Even more importantly, we used the three-dimensional (3D) fibrin gel to enrich the tumor-repopulating cells (TRCs) to validate the expression of the signature in CSCs by quantitative RT-PCR. mRNAsi was significantly elevated in tumor and high-mRNAsi score was associated with poor overall survival in HCC. The positive stemness-associated (blue) module with 737 genes were screened based on WGCNA, and Budding uninhibited by benzimidazoles 1 (BUB1) was identified as the hub gene highly related to stemness in HCC. Then, the prognostic value and stemness characteristics were well validated in the ICGC and GSE14520 cohorts. Further analysis showed the expression of BUB1 was elevated in TRCs. BUB1, as a potential stemness-associated biomarker, could serve as a therapeutic CSCs-target and predicted the clinical outcomes of patients with HCC. | Authentic |
Text : Aberrant expression of long noncoding RNA (lncRNA) is associated with carcinogenesis of various tumors. The aim of current study was to explore the clinical significance and biological function of long non-coding RNA HOST2 (lnc-HOST2) in patients with osteosarcoma. The expression of lnc-HOST2 was detected by quantitative Real-time PCR (qRT-PCR) in 163 osteosarcoma specimens and matched the normal tissues. The significance of lnc-HOST2 as a prognostic factor as well as its relationship with survival was determined. The effects of lnc-HOST2 expression on the biological behavior of osteosarcoma cells were investigated by MTT and flow cytometry. qRT-PCR and Western blot were used to evaluate the mRNA and protein expression of apoptosis-related factors. The expression levels of lnc-HOST2 in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissues (p < 0.01). Statistical assay indicated that the expression level of lnc-HOST2 was positively correlated with tumor stage (p = 0.003) and distant metastasis (p = 0.000). Furthermore, Kaplan-Meier analysis suggested that patients with high lnc-HOST2 showed poorer overall survival than those with low lnc-HOST2 (p = 0.000). The univariate and multivariate analysis further revealed that lnc-HOST2 expression was an independent prognostic factor for overall survival. Then, functionally, down-regulation of lnc-HOST2 suppressed proliferation and induced cell apoptosis in osteosarcoma cells. Notably, we confirmed that up-regulation of lnc-HOST2 led to Bcl-2 downregulation and Bax upregulation in osteosarcoma cells. We provided the first evidence that lnc-HOST2 may serve as a novel prognostic marker in osteosarcoma. Further, targeting lnc-HOST2 may represent an attractive target therapy for osteosarcoma. | Authentic |
Text : Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. In this paper, selenium nanoparticles (SeNPs) was linked with hyaluronic acid (HA) to prepare tumor-targeted delivery vehicle HA-SeNPs, and HA-SeNPs was loaded with paclitaxel (PTX) to fabricate functionalized selenium nanoparticles HA-Se@PTX. HA-Se@PTX showed greater uptake in A549 cells in comparison with that in HUVEC, verifying HA-mediated specific uptake of HA-Se@PTX. HA-Se@PTX was capable of entering A549 cells via clathrin-associated endocytosis and showed faster drug release in cancer cell microenvironment in comparison with normal physiological environment. HA-Se@PTX could obviously inhibit the proliferation, migration and invasion of A549 cells and trigger A549 cells apoptosis. Moreover, active targeting functionalized selenium nanoparticles HA-Se@PTX showed greater in vivo antitumor activity compared with free PTX or passive targeting delivery system Se@PTX. In addition, HA-Se@PTX exhibited negligible toxicity on the major organs of mice. In a word, HA-Se@PTX may develop into a valuable nanoscale antitumor drug agent for lung cancer treatment. | Authentic |
Text : Breast cancer is one of the most common cancers in women all over the world. Due to the improvement of medical treatments, most of the breast cancer patients would be in remission. However, the patients have to face the next challenge, the recurrence of breast cancer which may cause more severe effects, and even death. The prediction of breast cancer recurrence is crucial for reducing mortality. This paper proposes a prediction model for the recurrence of breast cancer based on clinical nominal and numeric features. In this study, our data consist of 1,061 patients from Breast Cancer Registry from Shin Kong Wu Ho-Su Memorial Hospital between 2011 and 2016, in which 37 records are denoted as breast cancer recurrence. Each record has 85 features. Our approach consists of three stages. First, we perform data preprocessing and feature selection techniques to consolidate the dataset. Among all features, six features are identified for further processing in the following stages. Next, we apply resampling techniques to resolve the issue of class imbalance. Finally, we construct two classifiers, AdaBoost and cost-sensitive learning, to predict the risk of recurrence and carry out the performance evaluation in three-fold cross-validation. By applying the AdaBoost method, we achieve accuracy of 0.973 and sensitivity of 0.675. By combining the AdaBoost and cost-sensitive method of our model, we achieve a reasonable accuracy of 0.468 and substantially high sensitivity of 0.947 which guarantee almost no false dismissal. Our model can be used as a supporting tool in the setting and evaluation of the follow-up visit for early intervention and more advanced treatments to lower cancer mortality. | Authentic |
Text : The 3D convolutional neural network is able to make use of the full nonlinear 3D context information of lung nodule detection from the DICOM (Digital Imaging and Communications in Medicine) images, and the Gradient Class Activation has shown to be useful for tailoring classification tasks and localization interpretation for fine-grained features and visual explanation for the internal working. Gradient-weighted class activation plays a crucial role for clinicians and radiologists in terms of trusting and adopting the model. Practitioners not only rely on a model that can provide high precision but also really want to gain the respect of radiologists. So, in this paper, we explored the lung nodule classification using the improvised 3D AlexNet with lightweight architecture. Our network employed the full nature of the multiview network strategy. We have conducted the binary classification (benign and malignant) on computed tomography (CT) images from the LUNA 16 database conglomerate and database image resource initiative. The results obtained are through the 10-fold cross-validation. Experimental results have shown that the proposed lightweight architecture achieved a superior classification accuracy of 97.17% on LUNA 16 dataset when compared with existing classification algorithms and low-dose CT scan images as well. | Authentic |
Text : Leflunomide (LEF), an inhibitor of dihydroorotate dehydrogenase (DHODH) in pyrimidine biosynthetic pathway, is an immunomodulatory agent approved for the treatment of rheumatoid arthritis. In this study, we show that LEF significantly reduced cell proliferation of renal carcinoma cells in a concentration-dependent manner. LEF at 50 μM induced S-phase arrest and autophagy. Higher doses of LEF (>50 μM) effectively induced cell apoptosis. Modulating the concentration of LEF resulted in distinct effects on the expression of regulatory proteins associated with cell cycle, apoptosis, and autophagy. In particular, high concentrations of LEF inhibited canonical WNT signaling by promoting nucleo-cytoplasmic shuttling and proteasome-dependent degradation of β-catenin. Mechanistic studies showed that the repression of AKT activation partly accounted for LEF-mediated WNT inhibition. Gene expression microarray revealed that LEF treatment greatly inhibited the expression of FZD10 gene, a receptor mediating WNT/β-catenin activation. In vivo xenograft study in NOD/SCID mice further validated the inhibitory effects of LEF on tumor growth and Wnt/β-catenin signaling. However, LEF treatment also triggered cell autophagy and elevated the expression of WNT3a, which ameliorated its cytotoxic effects. The combination of LEF with a WNT inhibitor IWP-2 or autophagy inhibitor HCQ could yield an enhanced anti-tumor outcome. Taken together, these results identify the potential utility and pharmacological feature of LEF in the chemotherapy of renal cell carcinoma (RCC). | Authentic |
Text : Targeting nuclear factor kappa B (NF-κB) signaling pathway has become a promising strategy for the development of new antitumor drugs. In this paper, we found that anti-infection drug furazolidone (FZD) could significantly inhibit NF-κB-driven luciferase activity, and FZD could markedly inhibit both of the constitutive and tumor necrosis factor-α (TNFα)-triggered phosphorylation of NF-κB p65 in small cell lung cancer (SCLC). Further studies revealed that FZD inhibited the expression of inhibitor of kappa B kinase β (IKKβ) in SCLC cells. In addition, we found that FZD had significant antitumor activities in SCLC cells. FZD could markedly suppress the cell viability of SCLC cells dose-dependently, and FZD could significantly induce the cleavages of poly ADP-ribose polymerase (PARP) and Caspase3, the biomarkers of cell apoptosis, in SCLC cells. The flow cytometry also revealed that FZD induced cell apoptosis in SCLC cells. Finally, we also found that overexpression of constitutively activated IKKβ could significantly abolish FZD-induced cell growth inhibition in SCLC cells, which further confirmed that FZD displayed its anti-SCLC activity through regulating NF-κB signaling pathway. | Authentic |
Text : Previous study has shown LEPR is a candidate gene of prediction and treatment of gastric cancer (GC). The purpose of this study was to test whether LEPR methylation could predict the risk of GC. Tumor tissues and 5-cm adjacent non-tumor tissues from 117 newly diagnosed and untreated GC patients were collected for the current methylation study. LEPR methylation levels were determined by quantitative methylation specific PCR (qMSP), and the methylation level of LEPR was described by the percentage of methylated reference (PMR). Our results showed that LEPR methylation levels were significantly lower in tumor tissues than those in adjacent non-tumor tissues (median PMR: 36.64% vs. 50.29%, P = 1E-4). In addition, LEPR methylation levels were found to be significantly associated with platelet (r = -0.198, P = .037). Further subgroup analysis showed that the association of LEPR promoter hypomethylation with GC was specific to males (males: P = 7E-5; females: P = .500). Notably, significant hypomethylation of LEPR promoter was found only in GC patients without recurrence (P = .002) but not in GC patients with recurrence (P = .146). The AUC of LEPR hypomethylation for identification of GC risk was 0.649 with a sensitivity of 67.5% and a specificity of 63.2%. In addition, the AUC of LEPR hypomethylation in males was 0.685 with a sensitivity of 68.4% and a specificity of 69.6%. LEPR hypomethylation can be used to predict the risk of GC in males. And it might also have the potential to predict the recurrence in GC patients. | Authentic |
Text : Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair. IGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring. The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC. We documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair. IL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair. | Authentic |
Text : Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients. 13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed. RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline. In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli. | Authentic |
Text : Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) has gained more attention in recent years due to its oncogenic roles in various cancers. MicroRNA-144 (miR-144) participates in the regulation of the growth of many cancer cells. This study investigated the interaction between lncRNA UCA1 and miR-144 in lung cancer cells. The potential downstream protein of miR-144 was also assessed. Our results found that lncRNA UCA1 was highly expressed in human lung cancer A549, H517, H4006, H1299, and H1650 cells compared to normal embryonic lung WI-38 and HEL-1 cells. Knockdown of lncRNA UCA1 significantly inhibited lung cancer A549 cell viability, migration, invasion, and cell cycle progression, but promoted cell apoptosis. Besides, we found that lncRNA UCA1 was bound to miR-144. miR-144 participated in the regulation effects of lncRNA UCA1 on A549 cell viability, migration, invasion, cell cycle transition, and cell apoptosis. In addition, Pre-B-cell leukemia homeobox 3 (PBX3) was found to be a direct target gene of miR-144. Overexpression of PBX3 promoted A549 cell proliferation and metastasis. Suppression of PBX3 had an opposite effect. | Authentic |
Text : Recent studies have discovered a class of micro-RNAs (miRNAs), which are dysregulated in various tumors and associated with carcinogenesis. In our research, we aim to uncover the molecular functions of miR-532-5p in glioma development. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect miR-532-5p expression in 48 glioma samples and 4 glioma cell lines. The Pearson's Chi-square test was used to determine the association of miR-532-5p expression with several clinicopathological indexes in glioma patients. Besides, cell proliferation assay, colony formation assay, and Ethynyl deoxyuridine (EdU) incorporation assay were performed to explore in vitro effects of miR-532-5p on glioma cells. Furthermore, the interaction between miR-532-5p and CSF1 in glioma was studied by performing Western blot assay and Dual-Luciferase Reporter Gene Assay. Downregulated miR-532-5p expression was observed in glioma tissues compared with adjacent normal samples. MiR-532-5p expression was associated with the KPS score and tumor grading in glioma patients. Moreover, cell proliferation of glioma was inhibited after overexpression of miR-532-5p in vitro. Furthermore, CSF1 was a target of miR-532-5p in glioma. After overexpression of miR-532-5p, CSF1 was downregulated at mRNA and protein levels in vitro Besides, the expression of CSF1 in glioma tissues was negatively related to that of miR-532-5p. Malignant phenotypes of glioma cells were remarkably suppressed through the overexpression of miR-532-5p. MiR-532-5p/CSF1 axis was identified as a new therapeutic intervention for the treatment of glioma. | Counterfeit |
Text : Fanconi Anemia (FA) is a rare genetic disorder characterized by developmental defects, bone marrow failure and high predisposition to cancer. The FA DNA repair pathway is required in humans to coordinate repair of DNA interstrand cross-links. The central event in the activation of the pathway is the monoubiquitination of FANCD2 and FANCI by the E2-E3 pair, Ube2T-FANCL, with the central UBC-RWD (URD) domain of FANCL recognizing the substrates. Whole genome sequencing studies of cancer cells from patients identified point mutations in the FANCL URD domain. We analysed 17 such variants of FANCL, including known substrate binding mutants (W212A, W214A and L248A, F252A, L254A, I265A), a FA mutation (R221C) and 14 cancer-associated mutations (F110S, I136V, L149V, L154S, A192G, E215Q, E217K, R221W, T224K, M247V, F252L, N270K, V287G, E289Q) through recombinant expression analysis, thermal shift assay, interaction with FANCD2, in vitro ubiquitination activity, and cellular sensitivity to an interstrand cross-linking agent. We find that the FANCL mutations I136V, L154S, W212A and L214A, R221W, R221C, and V287G are destabilizing, with N270K and E289Q destabilizing the C-terminal helices of the URD domain. The hydrophobic patch mutant (L248A, F252A, L254A, I265A), along with mutations E217K, T224K, and M247V, cause defects in the catalytic function of FANCL. This highlights the C-terminal lobe of the FANCL URD domain as important for the activity and function of FANCL. These mutations which affect the fold and activity of FANCL may contribute to tumorigenesis in these non-FA cancer patients, and this implicates FA genes in general cancer progression. | Authentic |
Text : Transarterial chemoembolization (TACE) is the most common treatment for patients with HCC who are unsuitable for radical therapies. Conventional TACE (cTACE) takes advantage of the preferential hepatic arterial supply of HCC for the targeted delivery of chemotherapeutic agents suspended in lipiodol, followed by embolization or reduction of arterial flow using various types of particles while sparing the surrounding liver parenchyma. Aims and Objectives. The current study is aimed at comparing the efficacy and safety profiles of transarterial infusion of recombinant human type-5 adenovirus (H101-TACE) with conventional transarterial chemoembolization (cTACE) in patients with unresectable hepatocellular carcinoma (HCC). Unresectable HCC patients that received H101-based TACE or cTACE from August 2018 to September 2021 were retrospectively evaluated. Propensity score matching (PSM) has a 1 : 1 ratio to eliminate possible confounder imbalances across cohorts. The main outcome was overall survival (OS), while secondary outcomes were progression-free survival (PFS) and tumor response. This study included 111 patients classified across two cohorts: the H101-TACE cohort (n = 37) and the cTACE cohort (n = 74). Median OS within the H101-TACE cohort was 9.0 months longer than within the cTACE cohort before PSM (22.1 vs. 13.1 months, P = 0.043) and 9.3 months longer following PSM (22.1 vs. 12.8 months, P = 0.004). The median PFS within the H101-TACE cohort was 3.2 months longer compared to the cTACE cohort before PSM (6.5 vs. 3.3 months, P = 0.046) and 2.5 months after PSM (6.5 vs. 4.0 months, P = 0.012). The disease control rate for H101 and control cohorts was 81.1% and 59.5%, accordingly (P = 0.039). The present study demonstrated that the H101-TACE is safe and efficient and can considerably enhance prognostic results for unresectable HCC compared to cTACE. | Authentic |
Text : Gastric cancer is the fourth most common type of cancer and the second highest leading cause of cancer-related deaths worldwide. It has already been established that miR-133a is involved in gastric cancer. In this study, we investigated the molecular mechanisms by which miR-133a inhibits the proliferation of gastric cancer cells. We analyzed the proliferative capacity of human gastric cancer cells SNU-1 using an MTT assay. Cell apoptosis was determined using flow cytometry. The expression levels of ERBB2, p-ERK1/2, and p-AKT in SNU-1 cells were determined using Western blot analysis. To confirm that ERBB2 is a direct target of miR-133a, a luciferase reporter assay was performed. Results showed that miR-133a overexpression inhibited SNU-1 cell proliferation and increased apoptosis. ERBB2 was a direct target of miR-133a, and it was negatively regulated by miR-133a. Interestingly, ERBB2 silencing has a similar impact to miR-133a overexpression, in that it significantly induced apoptosis and inhibited ERK and AKT activation. Our study showed that miR-133a inhibits the proliferation of gastric cancer cells by downregulating the expression of ERBB2 and its downstream signaling molecules p-ERK1/2 and p-AKT. Therefore, miR-133a might be used as a therapeutic target for treating gastric cancer. | Authentic |
Text : Circular RNA (circRNA) is involved in a wide range of life processes including tumorigenesis. However, the molecular mechanisms of circRNA in endometrial carcinoma (EC) carcinogenesis remain unclear. In the present study, we aimed to investigate the potential modulation of hsa_circ_0002577 on EC progression. Here, we showed that hsa_circ_0002577 expression was significantly upregulated in EC tissues, and high hsa_circ_0002577 expression was associated with advanced FIGO stage, lymph node metastasis, and poor overall survival rate of EC patients. In function assays, we demonstrated that hsa_circ_0002577 knockdown significantly reduced EC cells proliferation, migration, invasion ability in vitro and decreased tumor growth in vivo. In mechanism study, we revealed that hsa_circ_0002577 might act as a sponge for miR-197, and CTNND1 was revealed to be a target gene of miR-197. In addition, we revealed that the oncogenic effects of hsa_circ_0002577 were attributed to the regulation of miR-197/CTNND1/Wnt/β-catenin axis. Taken together, we indicated that hsa_circ_0002577 could play critical functions by hsa_circ_0002577/miR-197/CTNND1/Wnt/β-catenin signaling pathway, which served as a novel therapeutic application for EC treatment. | Authentic |
Text : Tumor necrosis factor-α (TNF-α)-induced protein 8-like 2 (TNFAIP8L2, TIPE2) is involved in the invasion and metastasis of human tumors. However, the functional role of TIPE2 in prostate cancer remains unclear. In the present study, we explored the role of TIPE2 in prostate cancer and cancer progression including the molecular mechanism that drives TIPE2-mediated oncogenesis. Our results showed that TIPE2 was lowly expressed in human prostate cancer tissues and cell lines. In addition, restored TIPE2 obviously inhibits proliferation in prostate cancer cells. TIPE2 overexpression also suppresses the epithelial-mesenchymal transition (EMT) process and migration/invasion in prostate cancer cells. Mechanistically, TIPE2 overexpression obviously inhibits the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K) and Akt in prostate cancer cells. In conclusion, for the first time we demonstrated that TIPE2 overexpression may suppress proliferation, migration, and invasion in prostate cancer cells by inhibiting the PI3K/Akt signaling pathway. Therefore, TIPE2 might serve as a potential therapeutic target for human prostate cancer. | Authentic |
Text : Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, have been established as first-line treatments for non-small cell lung cancer (NSCLC) patients and have exhibited notable clinical efficacy. However, resistance to TKIs has become one of the major obstacles in improving the therapeutic efficacy of patients with NSCLC. This study aims to investigate the role of the long non-coding RNA (lncRNA) LINC01116 in gefitinib resistance of NSCLC and explore its underlying mechanism. In this study, we found that LINC01116 is upregulated in the gefitinib-resistant NSCLC cells and tissues. Loss- and gain-of-function assays uncovered that LINC01116 downregulation sensitized gefitinib resistance, whereas the overexpression of LINC01116 conferred PC9/R cells to gefitinib resistance. Moreover, LINC01116 silencing increased IFI44 expression. Overexpression of IFI44 reversed the resistance to gefitinib in PC9/R cells, and rescue experiments confirmed that LINC01116 affects the gefitinib resistance of PC9/R cells partly dependent on regulating IFI44 expression. Moreover, downregulation of LINC01116 increased the sensitivity of PC9/R cells to gefitinib in vivo. Our study demonstrates that LINC01116 plays a critical role in gefitinib resistance of NSCLC cells by affecting IFI44 expression, providing a novel therapeutic target to overcome TKI resistance in NSCLC. | Authentic |
Text : The expression levels of estrogen receptor (ER α) are closely associated with estrogen-dependent growth, invasion and response to endocrine therapy in ERα-positive ovarian cancer. However, the underlying regulatory mechanisms remain to be fully understood. Previous studies have demonstrated that ERα is a direct target of microRNA (miR)-206. miR-206 has been found to be an important tumor suppressor in several cancer types, including ovarian, gastric and laryngeal cancer. However, the specific role of miR-206 in ovarian cancer remains unclear. The aim of the present study was to investigate the role of miR-206 in ER-a positive ovarian cancer in vitro. The present study demonstrated that miR-206 is significantly downregulated in ERα-positive but not ERα‑negative ovarian cancer tissues, compared with normal ovarian epithelium tissue. It was also found that the expression of miR-206 was decreased in ERα-positive ovarian cancer cell lines, CAOV-3 and BG-1, compared with normal ovarian epithelium tissues. This suggests that miR-206 may play a role in ERα-positive ovarian cancer cells via an estrogen-dependent mechanism. Further analysis revealed that 17β-E2 treatment significantly promoted cellular proliferation and invasion of estrogen-dependent CAOV-3 and BG-1 cells, which could be reversed by the introduction of miR-206 mimics. In conclusion, the present study suggests that miR-206 has an inhibitory role in estrogen-dependent ovarian cancer cells. Thus, miR-206 may be a promising candidate for the endocrine therapy of ERα-positive ovarian cancer. | Counterfeit |
Text : To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms. | Authentic |
Text : Immunotherapies for cancer, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to a long-lasting clinical response. But the therapeutic response rate remains low on account of many tumors that have evolved sophisticated strategies to evade immune surveillance. Solid tumors are characterized by the highly acidic microenvironment, which may weaken the effectiveness of antitumor immunity. Here, we explored a promising therapeutic development deployed by pH manipulation for avoiding immunoevasion. The highly acidified microenvironment of melanoma induces the expression of G-protein-coupled receptor (Ogr1) in T cells, which weakened their effective function and promote tumor growth. Ogr1 inhibition reactivate CD8+ T cells and have a cytotoxic role by reducing the activity of high glycolysis, resulting in comparatively low acidification of the tumor microenvironment, and leads to tumor suppression. In addition, the adoptive transfer of Ogr1-/--CD8+ T cells enhanced the antitumor responses, with the potential for immediate clinical transformation. | Authentic |
Text : Psoriasis is a multisystem disease affecting about 2% of the population, while keratin16 (KRT16) has been reported to participate in psoriasis. However, the specific mechanism of KRT16 in psoriasis was inadequately investigated. The objective of the study was to elucidate the mechanism by which siRNA-mediated silencing of KRT16 affects keratinocyte proliferation and vascular endothelial growth factor (VEGF) secretion in psoriasis through the extracellular signal-related kinase (ERK) signaling pathway. Psoriasis-related core gene KRT16 was screened out. Then, the expression of KRT16, VEGF, and ERK signaling pathway-related genes was detected in psoriatic patients. To further investigate the mechanism of KRT16, keratinocytes in psoriatic patients were treated with KRT16 siRNA or/and ERK inhibitor (PD98059) to detect the changes in related gene expression and cell survival. KRT16 was involved in psoriasis development. The expression levels of KRT16, p-ERK1/2, and VEGF in lesion tissues are significantly elevated. Keratinocytes treated with KRT16-siRNA and KRT16-siRNA + PD98059 exhibited reduced KRT16, p-ERK1/2, and VEGF expression. The cell survival rate in cells treated with KRT16-siRNA, PD98059, and KRT16-siRNA + PD98059 reduced significantly. These findings indicate that silencing KRT16 inhibits keratinocyte proliferation and VEGF secretion in psoriasis via inhibition of ERK signaling pathway, which provides a basic theory in the treatment of psoriasis. | Counterfeit |
Text : Increasing evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles during tumorigenesis in multiple types of cancers. However, little is known about the exact role of plasmacytoma variant translocation 1 (PVT1) in human pan-cancer. Here, we report the oncogenic role and function of PVT1 in human pan-cancer, including breast cancer. The expression of PVT1 in human tumor tissues and nontumor tissues, the upstream regulation of PVT1 and the relationship between its expression and prognosis and chemoresistance were examined by using The Cancer Genome Atlas data. PVT1 expression is higher in human cancer tissues compared with adjacent noncancerous tissues, and patients with high levels of PVT1 expression usually have tumors with a higher TNM stage. High PVT1 expression is also associated with worse disease outcomes in patients with cancer. Hypomethylation and transcription factor binding in the PVT1 promoter locus activates its transcriptional expression. Guilt by association analysis revealed that PVT1 may be involved in processes associated with tumorigenesis. Moreover, PVT1 may trigger chemoresistance in human cancer. These results indicated that PVT1 may act as an oncogenic driver and maybe a potential therapeutic target in human cancer. | Authentic |
Text : Hypoxia is a characteristic feature of solid tumors, leading to malignant behavior. During this process, HIF family members (HIFs) and the NF-κB pathway are activated. In addition, the hypoxia-associated factor (HAF) is reported to participate in the regulation of HIFs. However, the precise relationship among HIFs, HAF and the NF-κB pathway in bladder cancer (BC) remains unknown. In the current investigation, T24 BC cells were exposed to hypoxia, or by plasmid transfection to overexpress HAF or RelA (P65) to demonstrate their roles. The results indicate that hypoxia leads to the elevation of HAF plus activation of the NF-κB pathway, accompanied by the switch of HIF-1α to HIF-2α, resulting in the enhanced ability of malignancy in T24 cells. In order to further demonstrate the significance of this switch, HIF-1α and HIF-2α were co-transfected into T24 cells with HIF-β, respectively. The following results indicate that the T24hif-2α/β cells show enhanced ability of malignancy, accompanied by the maintenance of stem-cell markers, but the T24hif-1α/β cells show higher expression of metabolism-related genes. Boyden assays and wound-healing assays indicate the enhanced ability of malignancy for T24hif-2α/β. Thus, we conclude that on the hypoxic microenvironment, the switching of HIF-1α to HIF-2α, which is driven by HAF through activating the NF-κB pathway, contributes to the malignancy of T24 cells, accompanied by the maintenance of stem-cell markers. This provides us an avenue for understanding the progression of bladder cancer. | Authentic |
Text : With the gradual expansion of China's political, economic, and military strength, the rapid rise of China has become a globally recognized fact. At present, although China's international image as the world's second largest economy, military power, and political power has been increasingly accepted by the global community, China's image construction, as an important part of national soft power, is still facing many problems. This chapter focuses on defining the basic concepts of international publicity, China's soft power, and China's image construction in the context of new media integration, analyzes the international development trend of international publicity and the important functions and limitations of foreign publicity in establishing China's image construction, and analyzes the ecological environment of media integration development. Considering that there are great unfairness in the environment and the conflict of communication values is not conducive to the establishment of China's urban image, the article focuses on how to use global publicity values to establish China's national image and puts forward corresponding countermeasures. | Counterfeit |
Text : Cancer patients face multiple challenges, such as infertility caused by exposure to gonadotoxic agents and gonadal irradiation during cancer treatment. Little is known about the health practitioners' knowledge and practice regarding fertility preservation and its available options in Saudi Arabia. Thus, this study is designed to evaluate the level of knowledge, attitude, and practice (KAP) towards fertility preservation in cancer patients among health practitioners in an environmental region in Saudi Arabia. The cross-sectional study was carried out between September 2020 and January 2021. A self-administered questionnaire was distributed among health practitioners from a variety of specialties who work closely with cancer patients. Out of 100 participants, 90% need more knowledge about fertility preservation. The lack of fertility preservation clinics in the patient's area and its unaffordable expenses significantly influenced the health practitioners' attitude towards fertility preservation discussion with cancer patients. The results revealed that 92% of the participants agreed that the Saudi Ministry of Health should establish practice guidelines and provide fertility preservation services for cancer patients. The present study showed that clinical practitioners' knowledge remains insufficient. Education of health practitioners and the establishment of practice guidelines and fertility preservation clinics for cancer patients are required. | Authentic |
Text : Totally implantable intravenous ports (TIVAPs) are mostly used for long-term intravenous infusion therapy in cancer patients and can be left in the body for long periods of time for easy management, making them a simple and safe infusion device. Although the risks associated with long-term retention of fully implantable IV ports are less than those associated with other intravenous catheters, various complications may still occur at the time of implantation or during long-term use. To provide a scientific basis for clinical reduction of implantable intravenous port-associated infection complications by studying the risk factors for catheter-associated infection complications in patients applying implantable intravenous ports. A retrospective study was conducted on oncology patients treated with TIVAP at our hospital between January 2017 and November 2021, with a review of patients who were unplanned for extubation. Their demographic data, underlying disease status, and surgery-related data were counted to summarize and analyze the complications and related influencing factors of implantation and postimplantation. A total of 70 individuals with a mean age of 56.49 ± 12.19 years were included in the study. Among them, 39 were male and 64 had the highest percentage of epithelial tumors, followed by tumors of the lymphopoiesis system and mesenchymal tumors with 4 and 2 cases, respectively. Forty-eight of these patients did not have their ports removed as planned due to the occurrence of catheter-related hematogenous infections. In univariate analysis, BMI and neutropenia were risk factors for catheter-associated infections. In the multivariate analysis, BMI (OR = 1.38, 95% CI: 1.07-1.78, p=0.013) was an independent risk factor for catheter-associated infections. The overall complication rate of fully implanted intravenous ports was high, but most complications improved with symptomatic management, and no deaths due to port complications were identified. Infection was the most common complication, with catheter-associated bloodstream infection being the most common cause of unplanned port extraction. Patients with a higher BMI were at high risk of developing implantable IV port-associated infections, which may be an independent risk factor for implantable IV port-associated infections. | Authentic |