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Text : Cardiovascular diseases are closely associated with a high-cholesterol or high-fat diet. The aim of the present study was to investigate the cadioprotective effect of epigallocatechin-3-gallate (EGCG) in high-fat diet-fed rats, with special emphasis on myocardial infarction. A high-fat diet was administered to male Wistar rats for 45 days and the rats of the treatment group were administered EGCG via intraperitoneal injection for the last 15 days. The serum lipid profile, antioxidant enzyme activity, lipid peroxidation, lipid metabolic proteins and cardiac tissue markers were assessed. The myocardium and aorta were also histopathologically examined. The high-fat diet-fed rats were found to be hypercholesterolemic or exhibited abnormal values in the selected parameters. However, these abnormalities were reversed to near-normal values in the rats administered EGCG. Similarly, the enzymatic antioxidant activity and non-enzymatic antioxidant levels were improved with EGCG treatment in high-fat diet-fed rats. In addition, EGCG activated sirtuin 1, endothelial nitric oxide synthase and AMP-activated protein kinase α, which suggests that its protective effect is mediated through the stimulation of lipid metabolism. The histopathological examination further revealed that EGCG significantly prevented the development of tissue abnormalities and improved the morphology of myocardial tissue. Taken together, our results suggested that EGCG plays a significant role in the protection of the cardiovascular system against the high-fat diet. This is a preliminary study, emphasizing on the cardioprotective properties of EGCG. We are currently analyzing the molecular mechanism underlying the protective effects of EGCG. | Counterfeit |
Text : Recently cancer/testis antigens (CTA) have gained lots of attention as targets of immune therapy. However, the therapeutic efficacy of the CTAs single-antigen vaccines is not satisfying due to tumor heterogenicity. Therefore, many studies have focused on the enhancement of their efficacy by utilizing rich sources of tumor-associated antigens for anti-cancer vaccination. In the present study, the testicular germ cells and sperm cells as well-known sources of cancer/testis antigens were investigated for anti-4T1 breast cancer vaccination in BALB/c mice. The testicular germ cells (TGCs) and sperm cells were isolated from male BALB/c mice. The definite number of cells were homogenized and mixed with Bacillus Calmette-Guerin (BCG) for vaccination of female BALB/c mice. The treatment groups underwent 3 times of immunizations with one-week intervals and one week after the last injection, all groups were injected with 4T1 cancer cells. The TGCs + BCG (259.7 ± 39 mm3) and Sperm + BCG (426 ± 52 mm3) groups exhibited a significant decrease in the tumors' volume in comparison with BCG (641.3 ± 102 mm3) and no-treatment (788.1 ± 117 mm3) groups. Therefore, the TGCs + BCG immunized mice had the smallest tumors in comparison with all groups (P < 0.05). Also, the vital organs of TGCs + BCG (lungs: 6.8 ± 2, liver: 10.1 ± 2) immunized mice exhibited lowest metastatic burden in comparison with the Sperm + BCG (lungs: 13.5 ± 3, liver: 21.1 ± 4), BCG (lungs: 24.3 ± 4, liver: 33 ± 4), and no-treatment (lungs: 26.5 ± 6, liver: 37.3 ± 3) groups. These observations were inconsistent with the tumor-bearing mice survival evaluations as the TGCs + BCG group had longer mean survival time (79.6 ± 12 days) in comparison with other groups (no-treatment: 49.8 ± 8, BCG: 50.5 ± 10, BCG + Sperm: 64.6 ± 7 days). Therefore, TGCs can be a potential source of antigens for the anti-breast cancer immunization and more investigations are necessary. | Authentic |
Text : Circular RNAs (circRNA)are involved in the progression of cancers, and previous study showed that hsa_circ_0001649 expression is down-regulated in hepatocellular carcinoma (HCC). To explore whether hsa_circ_0001649 is a prognostic biomarker for HCC and to investigate the biological functions of hsa_circ_0001649 in HCC. Hsa_circ_0001649 expression was measured in 77 pairs of HCC and adjacent no-tumor tissues by quantitative Real-Time polymerase chain reaction. Kaplan-Meier curve and Cox regression were used to analyze its prognostic significance for HCC patients. In addition, the hsa_circ_0001649 was over-expressed using a circRNA-forming plasmid in HCC cells, and the biological function of hsa_circ_0001649 was investigated in vitro. We verified that hsa_circ_0001649 was down-regulated in HCC tissues compared with adjacent non-tumor tissues. In addition, low hsa_circ_0001649 expression was associated with the poor overall survival of HCC patients, and Cox multivariate analysis showed that hsa_circ_0001649 is a novel independent prognostic factor for HCC patients. Furthermore, the in vitro experiments demonstrated that over-expressed hsa_circ_0001649 inhibits the proliferation, migration, and invasion and promotes the apoptosis of HCC cells. Hsa_circ_0001649 could act as a novel prognostic biomarker for HCC patients. In addition, hsa_circ_ 0001649 might be a potential therapeutic target for HCC. | Authentic |
Text : Baicalin (BAI), a sort of flavonoid monomer, acquires from Scutellaria baicalensis Georgi, which was forcefully reported in diversified ailments due to the pleiotropic properties. But, the functions of BAI in osteoblast differentiation have not been addressed. The intentions of this study are to attest the influences of BAI in the differentiation of osteoblasts. MC3T3-E1 cells or rat primary osteoblasts were exposed to BAI, and then cell viability, ALP activity, mineralization process, and Runx2 and Ocn expression were appraised through implementing CCK-8, p-nitrophenyl phosphate (pNPP), Alizarin red staining, western blot, and RT-qPCR assays. The microRNA-217 (miR-217) expression was evaluated in MC3T3-E1 cells or rat primary osteoblasts after BAI disposition; meanwhile, the functions of miR-217 in BAI-administrated MC3T3-E1 cells were estimated after miR-217 inhibitor transfection. The impacts of BAI and miR-217 inhibition on Wnt/β-catenin and MEK/ERK pathways were probed to verify the involvements in BAI-regulated the differentiation of osteoblasts. BAI accelerated cell viability, osteoblast activity, and Runx2 and Ocn expression in MC3T3-E1 cells or rat primary osteoblasts, and the phenomena were mediated via activations of Wnt/β-catenin and MEK/ERK pathways. Elevation of miR-217 was observed in BAI-disposed MC3T3-E1 cells or rat primary osteoblasts, and miR-217 repression annulled the functions of BAI in MC3T3-E1 cell viability and differentiation. Additionally, the activations of Wnt/β-catenin and MEK/ERK pathways evoked by BAI were both restrained by repression of miR-217. These explorations uncovered that BAI augmented the differentiation of osteoblasts via activations of Wnt/β-catenin and MEK/ERK pathways by ascending miR-217 expression. | Counterfeit |
Text : Type 2-diabetic (T2D) disease has been reported to increase the incidence of liver cancer, however, the underlying pathophysiology is still not fully understood. Here, we aimed to reveal the underlying pathophysiology association between the T2D and hepatocellular carcinoma (HCC) and, therefore, to find the possible therapeutic targets in the occurrence and development of HCC. The methylation microarray data of T2D and HCC were extracted from the Gene Expression Omnibus and The Cancer Genome Atlas. A total of 504 differentially methylated genes (DMGs) between T2D samples and the controls were identified, whereas 6269 DMGs were identified between HCC samples and the control groups. There were 336 DMGs coexisting in diabetes and HCC, among which 86 genes were comethylated genes. These genes were mostly enriched in pathways as glycosaminoglycan biosynthesis, fatty acid, and metabolic pathway as glycosaminoglycan degradation and thiamine, fructose and mannose. There were 250 DMGs that had differential methylation direction between T2D DMGs and HCC DMGs, and these genes were enriched in the Sphingolipid metabolism pathway and immune pathways through natural killer cell-mediated cytotoxicity and ak-STAT signaling pathway. Eight genes were found related to the occurrence and development of diabetes and HCC. Moreover, the result of protein-protein interaction network showed that CDKN1A gene was related to the prognosis of HCC. In summary, eight genes were found to be associated with the development of HCC and CDKN1A may serve as the potential prognostic gene for HCC. | Authentic |
Text : Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, was firstly identified as a modulator of smooth muscle cell migration. Though the expression of EGFL7 was reported to be up-regulated during tumorigenesis, the clinical and biological functions of EGFL7 in pancreatic carcinoma (PC) were still not fully elucidated. In this study, we found that the serum EGFL7 level in PC tissues was statistically higher than that in normal subjects (p<0.001), and its level in non-resectable patients was also higher than that in resectable ones (p=0.013). Among these resectable PC patients, the postoperative EGFL7 expression was significantly down-regulated when tumors were resected (p=0.018). Using the immunohistochemistry method, our results demonstrated that the positive expression of EGFL7 was significantly associated with the TNM stage (p=0.024), lymph node metastasis (p=0.003) and local invasion (p=0.022), and the EGFL7 expression closely correlated to the micro-vessel density (MVD) in PC tissues by Spearman analysis (r=0.941, p=0.000). In vitro, EGFL7 was silenced by the small interference RNA in PC cells, and our data indicated that down-regulation of EGFL7 did not influence the cycle progression, proliferation, colony formation and apoptosis of PC cells (p>0.05), whereas inhibition of EGFL7 expression could decrease PaCa-2 cell invasion (p<0.05). More interestingly, by tubular formation, Chick embryo chorioallantoic membrane (CAM) and ELISA assays, our results revealed that silencing EGFL7 expression represented a strong inhibiting effect on tubular formation of micro-vessels through down-regulating the protein levels of VEGF and Ang-2 (p<0.05). Our results raised the possibility of using EGFL7as a potential prognostic biomarker and therapy target of PC, and down-regulation of EGFL7 might be considered to be a potentially important molecular treatment strategy for patients with PC. | Authentic |
Text : Medullary thyroid carcinoma (MTC) accounts up to 10% of all thyroid cancers, but is responsible for a disproportionate number of deaths. While surgery is the only curative treatment for MTC, indications for lateral neck lymph node (LLN) dissection are controversial. We performed a retrospective review to describe clinical outcomes in 93 MTC patients from July 1995 to March 2015. We analyzed their clinicopathologic factors, and cut-off values of tumor size and calcitonin levels were calculated using a receiver operating characteristic curve. Using the instances of lymph node metastases, the tumor size cut-off value was 0.95 cm (area under curve, AUC = 0.697) in patients with ipsilateral central lymph node (CLN) metastases, 2.25 cm (AUC = 0.793) in contralateral CLN metastases, and 1.75 cm (AUC = 0.753) in ipsilateral LLN metastases. The cut-off values of preoperative calcitonin levels were 226.6 pg/mL (AUC = 0.746) in ipsilateral CLN, 755.0 pg/mL (AUC = 0.840) in contralateral CLN metastases, and 237.0 pg/mL (AUC = 0.775) in ipsilateral LLN metastases. This study supports the notion that ipsilateral LLN metastases occur before contralateral CLN metastases. Therefore, ipsilateral LLN dissection should be considered in patients with contralateral CLN metastases. The extent of surgery should be based on the status of LN metastases, preoperative basal calcitonin level, and tumor size to help individualize the extent of surgery. | Authentic |
Text : Heat shock proteins (HSPs) are molecular chaperones that play a pivotal role in correct folding, stabilization and intracellular transport of many client proteins including those involved in oncogenesis. HSP70, which is frequently overexpressed in prostate cancer (PCa), has been shown to critically contribute to tumor cell survival, and might therefore represent a potential therapeutic target. We treated both the androgen receptor (AR)-positive LNCaP and the AR-negative PC-3 cell lines with the pharmacologic HSP70 inhibitor VER155008. Although we observed antiproliferative effects and induction of apoptosis upon HSP70 inhibition, the apoptotic effect was more pronounced in AR-positive LNCaP cells. In addition, VER155008 treatment induced G1 cell cycle arrest in LNCaP cells and decreased AR expression. Further analysis of the HSP system by Western blot analysis revealed that expression of HSP27, HOP and HSP90β was significantly inhibited by VER155008 treatment, whereas the HSP40, HSP60, and HSP90α expression remained unchanged. Taken together, VER155008 might serve as a novel therapeutic option in PCa patients independent of the AR expression status. | Authentic |
Text : Recent findings suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into the microenvironment of developing tumors, where they contribute to metastatic processes. The aim of this study was to investigate the role of BM-MSCs in promoting osteosarcoma and hepatocellular carcinoma cell progression in vitro and the possible mechanisms involved in these processes. U2OS and SNU-398 are osteosarcoma and hepatocellular carcinoma cell lines, respectively, that can be induced to proliferate when cultured in the presence of BM-MSCs. To determine the effect of BM-MSCs on U2OS and SNU-398 cells, the AKT and ERK signaling pathways were investigated, and increases were observed in active P-Akt and P-Erk forms. Moreover, BM-MSCs caused an increase in tumor cell migration and invasion that was derived from the enhancement of CXCR4 levels. Thus, when tumor cells were treated with the CXCR4 antagonist AMD3100, a reduction in their migration and invasion was observed. Furthermore, a new CXCR4 inhibitor, Peptide R, which was recently developed as an anticancer agent, was used to inhibit BM-MSC-mediated tumor invasion and to overcome AMD3100 toxicity. Taken together, these results suggest that inhibiting CXCR4 impairs the cross-talk between tumor cells and BM-MSCs, resulting in reduced metastatic potential in osteosarcoma and hepatocellular carcinoma cells. | Authentic |
Text : To explore the cisplatin medical tolerance mechanism affecting bladder cancer cells. Bladder cancer cells were treated with protein kinase C α (PKCα) stimulation and inhibition agents. The small-interfering RNA (siRNA) inhibitory technique was used to differentiate and remove Netrin-1 from UNC5B. Cells treated by cisplatin were processed by the MIT method to estimate cell death and growth rate. The Western blot method was utilized to analyze PKCα, netrin-1, and UNC5B in bladder cancer cells, used in the relative control sample. Co-immunoprecipitation was employed to analyze PKCα, netrin-1, and UNC5B combination effects. PKCα high activity, netrin-1 high expression, and UNC5B with low expression can enhance bladder cancer cells cisplatin medical tolerance. PKCα low activity, netrin-1 low expression, and UNC5B with high expression can also enhance bladder cancer cells sensitivity to chemical therapeutic treatments. PKCα high activity with enhanced netrin-1 reduced UNC5B expression, and also enhanced netrin-1/UNC5B combination. It inhibits and/or deletes PKCα, Netrin-1 lower stream extracellular regulated protein kinases (ERK) signal, deletes UNC5B, PKCα, and lowers stream (ERK) signaling from activity. PKCα and netrin-1/UNC5B form a positive feedback control loop in relation to the regulation of cisplatin in bladder cancer cells. | Authentic |
Text : Previous studies have indicated that cancer may be promoted and/or exacerbated by inflammation and infection. The cytokines produced by activated innate immune cells that stimulate tumor growth and progression are considered as important components in this process. The interleukin (IL)-23/T helper (Th)17 axis, which exerts marked pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. Increasing clinical evidence indicates that Th17 may promote or inhibit tumor progression, however, the function of Th17 in the pathogenesis of benign and malignant thyroid neoplasms remains unclear. The present study investigated the association between the IL-23/Th17 axis and neoplastic and non-neoplastic thyroid lesions using immunohistochemistry. A total of 131 thyroid biopsy specimens were analyzed, which revealed high IL-17 and IL-23 expression in differentiated thyroid cancer and medullary thyroid cancer tissues when compared with benign lesions, including follicular thyroid adenoma and goiter tissues. Furthermore, high IL-17 expression was associated with recurrence and mortality. These results indicate that the IL-23/Th17 axis exhibits a pivotal function in the development of thyroid neoplasms. | Authentic |
Text : Gold nanoparticles (Au-NPs) have been widely used in biomedical fields such as imaging, diagnosis, and treatment because of their special characteristics. Au-NPs can be synthesized using several methods, including the biological method, also called green or eco-friendly synthesis. Recent studies have reported the anticancer activity of biosynthesized Au-NPs, especially in lung cancer. This review focused on the advances in the antilung cancer activity of biosynthesized Au-NPs and its potential mechanisms. | Authentic |
Text : Background: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) plays a critical role in tumorigenesis and cancer progression. However, the prognostic roles in cancer patients are inconsistent or even controversial. Therefore, we performed a meta-analysis to investigate the prognostic value of PBK/TOPK in cancers. Methods: Literature search was performed using several online databases (PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar, National Knowledge Infrastructure and Wanfang) for eligible articles published up to May 1, 2018. The relationship between PBK/TOPK expression and prognosis in cancers was investigated by using pooled hazard ratios (HRs) with 95% confidence intervals (CIs) through STATA 12.0 software. Results: Totally 20 eligible studies were included in this meta-analysis. The pooled results showed that carriers with high protein expression of PBK/TOPK were significantly associated with poor OS (HR: 1.69, 95% CI: 1.33-2.04) in various cancers, and patients with increased PBK/TOPK protein expression were significantly correlated with inferior RFS (HR: 1.63, 95% CI: 1.02-2.24) and short DFS (HR: 1.69, 95% CI: 1.16-2.23). Conclusions: The findings suggest that PBK/TOPK protein expression might serve as a prognostic tumor marker in cancers. | Authentic |
Text : Estimates of cervical lymph node (LN) metastasis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) are important. A nomogram is a useful tool for individualized prediction. A total of 235 patients were enrolled in this study. Univariate and multivariate analyses were performed to screen for independent risk factors and construct a nomogram to predict the risk of cervical LN metastasis. The nomogram performance was assessed by discrimination, calibration, and clinical use. Totally, four independent predictors, including the maximum diameter of tumor, paraesophageal lymph node status, recurrent laryngeal nerve lymph node status, and the CT-reported cervical LN status, were enrolled in the nomogram. The AUC of the nomogram model in the training and validation dataset were 0.833 (95% CI 0.762-0.905), 0.808 (95% CI 0.696-0.920), respectively. The calibration curve demonstrated a strong consistency between nomogram and clinical findings in predicting cervical LN metastasis. Decision curve analysis demonstrated that the nomogram was clinically useful. We developed a nomogram that could be conveniently used to predict the individualized risk of cervical LN metastasis in patients with middle and lower thoracic ESCC. | Authentic |
Text : The present study aimed to establish an induced pluripotent stem cell (iPSC) line from acute myelogenous leukemia (AML) cells in vitro and identify their biological characteristics. Cells from the AML-infiltrated skin from an M6 patient were infected with a lentivirus carrying OCT4, SOX2, KLF4 and C-MYC to induce iPSCs. The characteristics of the iPSCs were confirmed by alkaline phosphatase (ALP) staining. The proliferation ability of iPSCs was detected with a CCK-8 assay. The expression of pluripotency markers was measured by immunostaining, and the expression of stem cell-related genes was detected by qRT-PCR; distortion during the induction process was detected by karyotype analysis; the differentiation potential of iPSCs was determined by embryoid body-formation and teratoma-formation assays. ALP staining confirmed that these cells exhibited positive staining and had the characteristics of iPSCs. The CCK-8 assay showed that the iPSCs had the ability to proliferate. Immunostaining demonstrated that iPSC clones showed positive expression of NANOG, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. qRT-PCR results revealed that the mRNA expression of Nanog, Lin28, Cripto, FOX3, DNMT3b, DPPA2, and DPPA4 significantly increased in iPSCs. Karyotype analysis found no chromosome aberration in the iPSCs. The results of the embryoid body-formation and teratoma-formation assays indicated that the iPSCs had the potential to differentiate into all three germ layers. Our study provided evidence that an iPSC line derived from AML cells was successfully established. | Authentic |
Text : Osteoarthritis (OA) is one of the most common chronic degenerative diseases. Many studies have demonstrated the role of microRNAs (miRNAs) in OA; however, the role of miR-302b in OA remains elusive. The aim of this study was to identify the role of miR-302b in LPS-induced injury in chondrocytes. Human OA chondrocytes (C28/12 cell line) were transfected with miR-302b inhibitor and miR-302b mimic to investigate the effects of miR-302b expression on chondrocyte apoptosis and inflammation, and to identify the miR-302b target proteins. LPS treatment of chondrocytes significantly reduced cell viability and increased apoptotic rate. LPS treatment also increased the expression of inflammatory cytokines compared to control. miR-302b was up-regulated in LPS-induced chondrocytes. miR-302b was either suppressed or overexpressed in LPS-induced chondrocytes by transient transfection. miR-302b mimic transfection accelerated the effects of LPS on cell viability, apoptosis and inflammation. Of contrast, miR-302b inhibition represented a reverse effect. Dual luciferase activity demonstrated that Smad3 is a direct target for miR-302b and its expression was negatively regulated by miR-302b. In addition, miR-302b inhibition suppressed inflammation in LPS treated chondrocytes by up-regulating Smad3 expression. Moreover, LPS induced down-regulation of Notch and mTOR signaling pathway-related protein expressions, and miR-302b inhibition increased the expressions of Notch and mTOR signaling pathway-related proteins. We further found that miR-302b negatively regulated Notch2 levels through direct targeting its 3'UTR. These results suggest that miR-302b suppression may function as a protector in suppressing the inflammation during the development and progression of OA by up-regulating the target Smad3 expression. | Counterfeit |
Text : Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates. Pro-oncogenic OCT4A effects were expression-level dependent and accompanied by distinct chromosomal aberrations. OCT4A overexpression in medulloblastoma cells also induced a marked differential expression of non-coding RNAs, including poorly characterized long non-coding RNAs and small nucleolar RNAs. Altogether, our findings support the relevance of pluripotency-related factors in the aggravation of medulloblastoma traits classically associated with poor clinical outcome, and underscore the prognostic and therapeutic value of OCT4A in this challenging type of pediatric brain cancer. | Authentic |
Text : Pancreatic cancer (PC) stands out as one of the most lethal cancers. Due to late diagnosis, only a fraction of patients can be resected. Although it still has significant adverse effects and poor results, the treatment is connected with better overall survival than the prior treatment. Thus, new alternative therapy for advanced PC is needed. Materials/Methods. The impact of 10058-F4 and curcumin combination therapy on apoptosis and cell growth in SW1990 pancreatic cancer cells were determined in vitro using the CCK-8 assay and flow cytometry of Annexin V-FITC/PI, and the in vivo antitumor effect was determined utilizing SW1990-bearing pancreatic tumor mouse models induced by subcutaneous implantation. At concentrations of (10 mol/L+2 mol/L), 10058-F4+curcumin obtained the highest rate of SW1990 cell death, and they had a beneficial effect on SW1990 pancreatic tumor-bearing animals. Furthermore, c-Myc, Akt phosphorylation, and the expression of apoptosis-related molecular were reduced, and the combination therapy modified the expression of apoptosis-related molecular. In vitro and in vivo, the combination of 10058-F4 plus curcumin has antipancreatic cancer actions that are substantially effective. | Authentic |
Text : The aim of this study was to research the effects of microRNA-10a (miR-10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF-TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR-10a mimics, miR-10a inhibitors, K252a, and miR-10a inhibitors + K252a groups. Expressions of miR-10a, p38, PSD95, BDNF, cAMP-response element-binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT-qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit-8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR-10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR-10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR-10a mimics and K252a groups. Compared with the blank and NC group, the miR-10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR-10a inhibitors group presented an opposite trend to the miR-10a mimics and K252a groups. The synapse was complete and abundant in the miR-10a inhibitors group while disappeared in the miR-10a mimics and K252a groups. The results indicated that miR-10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF-TrkB signaling pathway. | Counterfeit |
Text : The immune checkpoint blockade is an effective strategy to enhance the anti‑tumor T cell effector activity, thus becoming one of the most promising immunotherapeutic strategies in the history of cancer treatment. Several immune checkpoint inhibitor have been approved by the FDA, such as anti‑CTLA‑4, anti‑PD‑1, anti‑PD‑L1 monoclonal antibodies. Most tumor patients benefitted from these antibodies, but some of the patients did not respond to them. To increase the effectiveness of immunotherapy, including immune checkpoint blockade therapies, miniaturization of antibodies has been introduced. A single‑domain antibody, also known as nanobody, is an attractive reagent for immunotherapy and immunoimaging thanks to its unique structural characteristic consisting of a variable region of a single heavy chain antibody. This structure confers to the nanobody a light molecular weight, making it smaller than conventional antibodies, although remaining able to bind to a specific antigen. Therefore, this review summarizes the production of nanobodies targeting immune checkpoint molecules and the application of nanobodies targeting immune checkpoint molecules in immunotherapy and immunoimaging. | Authentic |
Text : Multiple clinical and experimental studies have suggested that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may be effective at treating advanced non-small cell lung cancer (NSCLC), however, the molecular basis of primary resistance to EGFR-TKIs in NSCLC remains unclear. In the current study, the insulin-like growth factor 1 receptor (IGF-1R) gene in the gefitinib-resistant human lung adenocarcinoma epithelial cell line A549 (A549/GR) was silenced using small interfering RNA (siRNA) in order to determine the role of microRNA (miRNA) in the development of resistance against epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The relative gefitinib-resistant capacity in A549 and A549/GR cells was determined using a cell counting kit 8. A549/GR cells were transfected with chemically synthesized siRNA to silence the IGF-1R gene. A total of 48 h after siRNA transfection, IGF-1R expression in A549/GR cells was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. miRNA expression in A549/GR cells and A549/GR cells with silenced IGF-1R was analyzed using a miRNA microarray. The microarray results of 10 miRNAs were then compared with the results of RT-qPCR. The results demonstrated that the gefitinib-resistance capacity of A549/GR cells was six times higher than that of A549 cells. Additionally, RT-qPCR and western blotting demonstrated that the IGF-1R gene in A549/GR cells was successfully silenced by siRNA. The highest silencing rate (72%) of the IGF-1R gene was obtained using siRNA-2. The microarray identified 72 miRNAs with significantly different expression in A549/GR cells with silenced IGF-1R compared with A549/GR cells. Of the 72 differentially expressed miRNAs, 13 miRNAs (including miR-497-3p and miR-1273c) were up-regulated and 59 miRNAs (including miR-361-3p and miR-345-3p) were down-regulated in A549/GR cells with silenced IGF-1R compared with A549/GR cells. The changes in the expression of 10 different miRNAs were confirmed by RT-qPCR. Thus, the present study successfully established an A549/GR cell line with silenced IGF-1R. The results suggest that a number of miRNAs associated with the IGF-1R signaling pathway, including miR-497-3p and miR-144-5p, were involved in the development of resistance against EGFR-TKIs in A549 cells. These miRNAs may provide novel targets to treat lung adenocarcinoma exhibiting resistance against EGFR-TKIs. | Authentic |
Text : Phosphatidylinositol 3-kinases (PI3Ks) are crucial coordinators of intracellular signalling in response to the extracellular stimulators. Hyperactivation of PI3K signalling cascades is one among the most ordinary events in human cancers. Focusing on the PI3K pathway remains both a chance and a challenge for cancer therapy. The high recurrence of phosphoinositide 3-kinase (PI3K) pathway adjustments in cancer has led to a surge in the progression of PI3K inhibitors. Recent developments incorporate a re-assessment of the oncogenic mechanisms behind PI3K pathway modifications. Receptor tyrosine kinases upstream of PI3K, the p110a catalytic fractional unit of PI3K, the downstream kinase, AKT, and therefore the negative regulator, PTEN, are all often altered in cancer. In this review, we consider about the phosphoinositide 3-kinases family and mechanisms of PI3K-Akt stimulation in cancer. | Authentic |
Text : Chronic myeloid leukemia (CML) is a stem cell disease of the bone marrow where mechanisms of inter-leukemic communication and cell-to-cell interactions are proposed to be important for optimal therapy response. Tunneling nanotubes (TNTs) are novel intercellular communication structures transporting different cargos with potential implications in therapy resistance. Here, we have investigated TNTs in CML cells and following treatment with the highly effective CML therapeutics tyrosine kinase inhibitors (TKIs) and interferon-α (IFNα). CML cells from chronic phase CML patients as well as the blast crisis phase cell lines, Kcl-22 and K562, formed few or no TNTs. Treatment with imatinib increased TNT formation in both Kcl-22 and K562 cells, while nilotinib or IFNα increased TNTs in Kcl-22 cells only where the TNT increase was associated with adherence to fibronectin-coated surfaces, altered morphology, and reduced movement involving β1integrin. Ex vivo treated cells from chronic phase CML patients showed limited changes in TNT formation similarly to bone marrow cells from healthy individuals. Interestingly, in vivo nilotinib treatment in a Kcl-22 subcutaneous mouse model resulted in morphological changes and TNT-like structures in the tumor-derived Kcl-22 cells. Our results demonstrate that CML cells express low levels of TNTs, but CML therapeutics increase TNT formation in designated cell models indicating TNT functionality in bone marrow derived malignancies and their microenvironment. | Authentic |
Text : Understanding the human connectome by parcellations allows neurosurgeons to foretell the potential effects of lesioning parts of the brain during intracerebral surgery. However, it is unclear whether there exist variations among individuals such that brain regions that are thought to be dispensable may serve as important networking hubs. We obtained diffusion neuroimaging data from two healthy cohorts (OpenNeuro and SchizConnect) and applied a parcellation scheme to them. We ranked the parcellations on average using PageRank centrality in each cohort. Using the OpenNeuro cohort, we focused on parcellations in the lower 50% ranking that displayed top quartile ranking at the individual level. We then queried whether these select parcellations with over 3% prevalence would be reproducible in the same manner in the SchizConnect cohort. In the OpenNeuro (n = 68) and SchizConnect cohort (n = 195), there were 27.9% and 43.1% of parcellations, respectively, in the lower half of all ranks that displayed top quartile ranks. We noted three outstanding parcellations (L_V6, L_a10p, and L_7PL) in the OpenNeuro cohort that also appeared in the SchizConnect cohort. In the larger Schizconnect cohort, L_V6, L_a10p, and L_7PL had unexpected hubness in 3.08%, 5.13%, and 8.21% of subjects, respectively. We demonstrated that lowly-ranked parcellations may serve as important hubs in a subset of individuals, highlighting the importance of studying parcellation ranks at the personalized level in planning supratentorial neurosurgery. | Authentic |
Text : Increasing incidence and mortality rates of pancreatic cancer (PC) highlight an urgent need for novel and efficient drugs. Retention in endoplasmic reticulum 1 (RER1) is an important retention factor in the endoplasmic reticulum (ER). However, it remains elusive whether RER1 is involved in the retention of disease-related proteins. We analyzed the expression level of RER1 in PC and adjacent tissues, and also employed Kaplan-Meier's analysis to identify the correlation between RER1 expression and overall survival rate. Cell proliferation, colony formation, tumor formation, scratch test, and transwell invasion assays were performed in RER1 knockdown cells and negative control cells. We hereby reported the important functions of RER1 in tumorigenesis and metastasis of PC, evidenced by inhibitory effects of RER1 knockdown on PC cell proliferation, migration and aggressiveness. Tumor formation was also significantly repressed in RER1 knockdown cells compared to control. Hypoxia-inducible factor (HIF)-1α was found to be an upstream regulator of RER1. Knockdown HIF-1α cells exhibited similar repressive impact on cell proliferation as RER1, and showed diminished migratory and invasive abilities under hypoxic condition. The present study has demonstrated that RER1 enhances the progression of PC through promoting cell proliferation, migration and aggressiveness. | Authentic |
Text : Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a positive regulatory role on cell autophagy through inhibiting PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. miR-155 plays a critical role in osteosarcoma occurrence and chemoresistance. Bioinformatics analysis revealed the targeted binding site between miR-155 and the 3'-UTR (untranslated region) of PTEN mRNA. This study investigated the role of miR-155 in regulating osteosarcoma cell autophagy, chemosensitivity to Adriamycin (ADM), and PTEN-PI3K/AKT/mTOR signaling pathway. Dual luciferase reporter gene assay confirmed the relationship between miR-155 and PTEN. MG-63 cells and drug-resistant MG-63/ADM cells were treated by ADM to compare miR-155, PTEN, p-AKT, p-mTOR, and Beclin-1 expressions. Cell apoptosis was tested by flow cytometry. MG-63/ADM cells were divided into five groups, including anti-miR-NC, anti-miR-155, pSicoR-blank, pSicoR-PTEN, and anti-miR-155+pSicoR-PTEN group. miR-155 targeted suppressed PTEN expression. miR-155, p-AKT, and p-mTOR significantly increased, while PTEN and Beclin-1 obviously reduced in MG-63/ADM cells compared with MG-63 cells. ADM treatment markedly elevated miR-155, p-AKT, and p-mTOR expressions, whereas reduced PTEN level. Beclin-1 was slightly upregulated, and autophagy and apoptosis levels were low. Anti-miR-155 and/or pSicoR-PTEN significantly enhanced PTEN and Beclin-1 expressions, cell apoptosis, and autophagy induced by ADM and declined p-AKT and p-mTOR levels. miR-155 targeted suppressed PTEN expression, enhanced PI3K/AKT/mTOR signaling pathway, inhibited cell apoptosis and autophagy induced by ADM, and reduced sensitivity to ADM. | Authentic |
Text : Aims: Our study aimed to investigate the expression and prognostic role of homeobox C6 (HOXC6) in prostate cancer (PCa). Methods: Relative expression of HOXC6 at mRNA and protein levels in tissues and cell lines of PCa were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. Association between HOXC6 expression and clinical factors was analyzed by Chi-square test. HOXC6 effects on the proliferation, invasion and metastasis of PCa cells were severally examined through CCK-8 and transwell assays. Results: Relative expressions of HOXC6 at mRNA and protein levels were obviously higher in both PCa tissues and cells than in adjacent non-cancerous tissues and normal human prostate epithelial cells (p < .05). Chi-square test demonstrated that high expression of HOXC6 was significantly associated with PSA concentration, Gleason score and TNM stage (p < .05). The down-regulation of HOCX6 remarkably inhibited the proliferation, migration and invasion of PCa cells. Kaplan-Meier analysis showed that patients with high HOXC6 expression had shorter overall survival than those with low HOXC6 expression (log rank test, p < .001). Conclusion: Up-regulated HOXC6, in PCa patients, could not only participate in the progression of PCa but also function as an independent prognostic marker for the cancer. | Authentic |
Text : To analyze the effects of deep hyperthermia combined with intraperitoneal chemotherapy on liver-kidney function, immune function, and long-term survival in patients with abdominal metastases. A total of 88 patients with abdominal metastases confirmed in the hospital were enrolled as the research objects between August 2018 and August 2021. They were randomly divided into control group (n = 44) and observation group (n = 44). The control group was treated with intraperitoneal chemotherapy, while observation group was additionally treated with deep hyperthermia. The general clinical data of patients were recorded. The short-term and long-term curative effects were evaluated. The occurrence of side effects in both groups was recorded. Before and after treatment, levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected by full-automatic biochemical analyzer. The level of blood urea nitrogen (BUN) was detected by the urease electrode method. The level of serum creatinine (Scr) was detected by the picric acid method. The levels of CD3 +, CD4 +, CD8 +, and NK cells were detected by BD FACSCalibur flow cytometer. There was no significant difference in clinical data between the two groups (P > 0.05). In the observation group, ORR was significantly higher than that in the control group (54.55% vs 29.55%) (P < 0.05), OS was significantly longer than that in the control group (P < 0.05), and median survival time and mPFS were longer than those in the control group. After treatment, the levels of ALT, AST, BUN, and Scr were significantly increased in the control group (P < 0.05), but there was no significant difference in peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio or count of NK cells before and after treatment (P > 0.05). Before and after treatment, there was no significant difference in the levels of ALT, AST, BUN, and Scr in the observation group (P > 0.05). After treatment, peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio and count of NK cells were all increased in the observation group, significantly higher than those in the control group (P < 0.05). The incidence of chemotherapy side effects in the observation group was significantly lower than that in the control group (P < 0.05). The short-term and long-term curative effects of deep hyperthermia combined with intraperitoneal chemotherapy are good on patients with intraperitoneal metastases, with less damage to liver-kidney function. It is beneficial to enhance immune function of patients, with mild side effects. | Counterfeit |
Text : In the last decade, several reports highlight the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in cancer aggressiveness and resistance. Specifically, in chronic myeloid leukemia, we have reported that high expression of the LMWPTP maintains Src and Bcr-Abl kinases in an activated status and the glucose metabolism is directed to lactate production and, in turn, favor the pentoses pathway (one of the key process for antioxidant and protective responses). In this present study, we investigated the possible correlation between the LMWPTP and autophagy. In resistant chronic myeloid leukemia cells, the antioxidant response is supported by the glycolytic metabolism and antioxidant enzymes such as SOD and catalase, both favored by the LMWPTP. Therefore, when the cells were challenged by hydrogen peroxide treatment, the LMWPTP level goes down as well as SOD, and in turn, autophagy process was stimulated. The findings presented here reveal a novel aspect by which LMWPTP cooperates for the resistance of CML towards stressor stimuli. | Authentic |
Text : Colorectal cancer (CRC) accounts for the highest fatality rate among all malignant tumors. Immunotherapy has shown great promise in management of many malignant tumors, necessitating the need to explore its role in CRC. Our analysis revealed a total of 71 differentially expressed IRGs, that were associated with prognosis of CRC patients. Ten IRGs (FABP4, IGKV1-33, IGKV2D-40, IGLV6-57, NGF, RETNLB, UCN, VIP, NGFR, and OXTR) showed high prognostic performance in predicting CRC outcomes, and were further associated with tumor burden, metastasis, tumor TNM stage, gender, age, and pathological stage. Interestingly, the IRG-based prognostic index (IRGPI) reflected infiltration of multiple immune cell types. This model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor prognosis of CRC. We performed a comprehensive analysis of expression profiles for immune-related genes (IRGs) and overall survival time in 437 CRC patients from the TCGA database. We employed computational algorithms and Cox regression analysis to estimate the relationship between differentially expressed IRGs and survival rates in CRC patients. Furthermore, we investigated the mechanisms of action of the IRGs involved in CRC, and established a novel prognostic index based on multivariate Cox models. | Authentic |
Text : Elderly patients with chronic diseases (CDs) have a higher predilection for falls, with more severe consequences once they fall. Therefore, it is necessary to explore an effective way to prevent falls in elderly patients with CDs. To clarify the clinical effects of outpatient health education on fall prevention and self-health management in elderly patients with CDs. This retrospective study enrolled 102 elderly patients with CDs who received treatment in the School of Medicine, Sir Run Run Shaw Hospital of Zhejiang University, between January 2019 and December 2020. Patients intervened by routine nursing were assigned to the regular group (n = 48), and those additionally treated with outpatient health education were included in the research group (n = 54). Assessment of patients' negative emotions (NEs) adopted the Self-Rating Anxiety/Depression Scale (SAS/SDS), determination of their sense of self-efficacy employed the Falls Efficacy Scale International (FES-I), and their self-care capacity evaluation used the Exercise of Self-Care Agency (ESCA). Patients' falls, hospitalization time, fall prevention knowledge, fall prevention-related health behavior, and nursing satisfaction were recorded. After the nursing intervention, lower SAS, SDS, and FES-I scores were determined in the research group versus the regular group; the total ESCA score assessed from various dimensions was higher in the research group; the research group also exhibited a markedly lower incidence of falls, and shorter hospitalization time than the regular group, with better mastery of fall prevention knowledge, fall prevention-related health behavior and nursing satisfaction. Outpatient health education intervention can prevent senile patients with CDs from falling, promote their rehabilitation, and enhance their mastery of fall prevention knowledge; moreover, it can improve patients' healthy behaviors to prevent falls, mitigate their NEs, and improve their sense of self-efficacy and self-care ability, which has high clinical application value. | Counterfeit |
Text : Colorectal cancer is the fourth most common type of cancer worldwide, and adenocarcinoma cells that form the majority of colorectal tumors are markedly resistant to antineoplastic agents. Epidemiological studies have demonstrated that consumption of fruits and vegetables that are rich in polyphenols, is linked to reduced risk of colorectal cancer. In the present study, the effect of a standardized anthocyanin (ACN)‑rich extract on proliferation, apoptosis and cell cycle in the Caco-2 human colorectal cancer cell line was evaluated by trypan blue and clonogenic assays and western blot analysis of cleaved caspase‑3 and p21Waf/Cif1. The results of the current study demonstrated that the ACN extract markedly decreased Caco‑2 cell proliferation, induced apoptosis by activating caspase‑3 cleavage, and upregulated cyclin‑dependent kinase inhibitor 1 (p21Waf/Cif1) expression in a dose dependent manner. Furthermore, ACN extract was able to produce a dose‑dependent increase of intracellular reactive oxygen species (ROS) in Caco‑2 cells, together with a light increase of the cell total antioxidant status. In conclusion, the present study demonstrated that a standardized berry anthocyanin rich extract inhibited proliferation of Caco‑2 cells by promoting ROS accumulation, inducing caspase‑3 activation, and upregulating the expression of p21Waf/Cif1. | Authentic |
Text : To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma. | Counterfeit |
Text : This study aimed to investigate the clinical significance of cullin 3 expression in nasopharyngeal carcinoma (NPC), as well as to explore the regulatory mechanism of cullin 3 underlying the growth and metastasis of NPC cells. Our findings showed that the expression levels of cullin 3 were significantly increased in both NPC tissues and cell lines. A strong positive correlation was found between cullin 3 expression and the Ki-67-based proliferation index in NPC tissues. Moreover, cullin 3 overexpression was correlated with local relapse and distant metastasis in NPC patients. In vitro experiments showed that knockdown of cullin 3 caused a significant reduction in the proliferation of NPC cells, probably by inducing cell cycle arrest. In addition, downregulation of cullin 3 inhibited colony formation and the migratory and invasive capacities of NPC cells. The expression levels of PCNA and epithelial-to-mesenchymal transition (EMT)-related proteins were also meditated by cullin 3 in NPC cells. Based on these findings, we demonstrated that cullin 3 plays a promoting role in the malignant progression of NPC and suggest that the cullin 3-based ubiquitin proteasome pathway may be used as a promising therapeutic target for NPC. | Authentic |
Text : A growing interest has emerged in the field of studying the cross-talk between cancer cell cycle and metabolism. In this review, we aimed to present how metabolism and cell cycle are correlated and how cancer cells get energy to drive cell cycle. Cell proliferation and cell death largely depend on the metabolic activity of the cell. Cell cycle proteins, e.g. cyclin D, cyclin dependent kinase (CDK), some pro-apoptotic and anti-apoptotic proteins, and P53 have been shown to be regulated by metabolic crosstalk. Dysregulation of this cross-talk between metabolism and cell cycle leads to degenerative disorder(s) and cancer. It is not fully understood the actual reason of aberration between metabolism and cell cycle, but it is a hallmark of cancer research. Herein, we discussed the role of some regulatory molecules relative of cell cycle and metabolism and highlight how they control the function of each other. We also pointed out, current therapeutic opportunities and some additional crucial therapeutic targets on these fields that could be a breakthrough in cancer research. | Authentic |
Text : Gall Bladder Cancer (GBC) is a type of extremely malignant tumor, which has high incidences of mortality. There is rare information about its mechanisms of invasion and gene expression regulations. microRNA-155 (miR-155) has mostly been reported to be over expressed in cases of solid tumors and hematopoietic malignancies. In this study, we have investigated the role and clinical significance of miR-155 in a Chinese population suffering from GBC and compared the results with nonneoplastic inflammation. Tissue specimens were collected on 50 patients of Gall Bladder Carcinoma and 10 patients suffering from nonneoplastic inflammation who have undergone surgeries at the Department of Pathology, Renji Hospital, Shanghai, from January 2019 to January 2020. We performed profiling of miR-155 expression in both nonneoplastic and gall bladder carcinoma tissues by QRT-PCR. Expression levels of miR-155 were found to be extremely high in GBC patients in comparison to the nonneoplastic tissues ( ∗ P < 0.05), as high miRNA is correlated with TNM stages. Further results noted were that miR-145-5p expressed genes mimic the gene expression of STAT1, a downregulation of IRF7 was noted in the GBC, and an activation of STAT1 was significantly noted in carcinoma cells of the gallbladder. Downregulation of PTPRF was also noted during the expression of miR-145. As downregulation of IRF7 is linked with low rates of survival, it was found that gall bladder carcinoma patients may face high mortality. The STAT-1 expression of unregulated in GBC patients was also noted. | Authentic |
Text : One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochemical characterization, biological effects, and mechanisms of action of four new analogs of conventional cisplatin, namely, cis-Pt(II) complexes containing either methyl or ethyl pyrazole N-donor ligands and chlorido or iodido ligands. It is noteworthy that while chlorido complexes display activity in a variety of cancer cell lines comparable to cisplatin, iodido complexes are considerably more potent due to their enhanced hydrophobicity and consequently enhanced cellular accumulation. Moreover, all of the studied Pt(II) alkylpyrazole complexes display a higher selectivity for tumor cells and effectively overcome the acquired resistance to cisplatin. Further results focused on the mechanism of action of the studied complexes and showed that in contrast to cisplatin and several platinum-based antitumor drugs, DNA damage by the investigated Pt(II)-alkylpyrazole complexes does not play a major role in their mechanism of action. Our findings demonstrate that inhibition of the tubulin kinesin Eg5, which is essential for forming a functional mitotic spindle, plays an important role in their mechanism of antiproliferative action. | Authentic |
Text : Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. | Authentic |
Text : As one of the deadliest malignancies, gastric cancer (GC) is often accompanied by a low 5-year survival following initial diagnosis, which accounts for a substantial proportion of cancer-related deaths each year worldwide. Altered epigenetic modifications of cancer oncogenes and tumor suppressor genes emerge as novel mechanisms have been implicated the pathogenesis of GC. In the current study, we aim to elucidate whether histone deacetylase 3 (HDAC3) exerts oncogenic role in GC, and investigate the possible mechanism. Initially, we collected 64 paired cancerous and noncancerous tissues surgically resected from GC patients. Positive expression of HDAC3, FTO, and MYC in the tissues was measured using Immunohistochemistry. Meanwhile, GC cell line BGC-823/AGS was selected and treated with lentivirus vectors for alteration of HDAC3, FTO, or FOXA2 expressions, followed by detection on mRNA and protein levels of HDAC3, FOXA2, FTO, and MYC using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The results demonstrated that the expressions of HDAC3, FTO and MYC were upregulated, while FOXA2 expression was downregulated in GC tissues and cells. After that, the cell viability, migration, and invasion of GC cells were assessed by CCK-8 and Transwell assays, revealing that HDAC3 accelerated GC cell viability, migration and invasion by degrading FOXA2. Subsequently, the binding relationship among HDAC3, FOXA2, FTO, and MYC was assessed by assays of immunoprecipitation, dual-luciferase reporter gene, and chromatin immunoprecipitation assay. Methylation of m6A mRNA in GC cells was detected via gene-specific m6A qPCR and dot-blot assays. The transcription factor FOXA2 was found to bind to the FTO gene promoter and decreased its expression, while FTO stabilized MYC mRNA by reducing m6A methylation of MYC in GC cells. In addition, HDAC3 was observed to maintain the FTO/m6A/MYC signaling and regulated GC progression, which was also supported by in vivo animal study data of GC cell tumorigenesis in nude mice. These key observations uncover the tumor-initiating activities of HDAC3 in GC through its regulation on FOXA2-mediated FTO/m6A/MYC axis, highlighting the potential of therapeutically targeting epigenetic modifications to combat GC. | Authentic |
Text : microRNA-493-3p (miR-493) has been reported to be critically downregulated in multiple types of human cancer. However, the expression level, biological roles and underlying mechanism of miR‑493 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. RT-qPCR was utilized for the determination of miR-493 expression in TSCC tissues and cell lines. The influence of miR-493 overexpression on TSCC cell proliferation, apoptosis, migration, invasion in vitro and tumor growth in vivo were explored via MTT assay, flow cytometry analysis, cell migration and invasion assays, and xenograft tumors in nude mice, respectively. Bioinformatics analysis, luciferase reporter assays, RT-qPCR and Western blotting were performed to clarify the potential mechanisms involved in the action of miR-493 in TSCC cells. miR-493 was significantly downregulated in TSCC tissues and cell lines. Decreased miR-493 expression was notably correlated with tumor differentiation, depth of invasion and TNM stage. Additionally, patients with TSCC having low miR-493 expression showed lower overall survival rate. Functionally, miR-493 upregulation inhibited TSCC cell proliferation, migration, invasion in vitro; induced cell apoptosis; and decreased the tumor growth in vivo. Bioinformatics analysis followed by luciferase reporter assays also demonstrated that miR-493 directly bound to the 3'-untranslated region of high-mobility group AT-hook 2 (HMGA2) in TSCC cells, and therefore reduced HMGA2 expression at the mRNA and protein level. Furthermore, HMGA2 was overexpressed in TSCC tissues and inversely correlated with miR-493. Moreover, silenced HMGA2 expression simulated the tumor-suppressing roles of miR-493 overexpression on TSCC cells. HMGA2 overexpression eliminated the inhibitory roles of miR-493 overexpression on TSCC cells. These observations demonstrated that miR-493 is a tumor suppressor inhibited the oncogenicity of TSCC cells by directly targeting HMGA2. These results provide sufficient evidence for the miR-493/HMGA2 axis as a novel therapeutic target for the treatment of patients with TSCC in the future. | Counterfeit |
Text : Stem cells from human exfoliated deciduous teeth (SHEDs) are highly proliferative, clonogenic, and multipotent stem cells with a neural crest cell origin. This property could be a desirable option for potential therapeutic applications. In this study, we focus on the effects of Rho kinase inhibitors Y-27632 and Noggin on the proliferation of SHEDs and their differentiation into neuron-like cells. SHEDs were extracted from 10 samples of deciduous teeth obtained from healthy children aged from 5 to 10. The passaged SHEDs were transfected with Noggin, Y-27632, or their combination. By means of MTT and colony formation assays, the effects of Y-27632 and Noggin on cell viability and colony formation were detected. Cellular morphology and neurosphere formation were observed under a microscope. Y-27632 transfection in SHEDs showed enhanced cell viability, colony formation, and neurosphere formation indicating that Y-27632 could promote cell proliferation of SHEDs. Furthermore, we observed that the SHEDs treated with Noggin in combination with Y-27632 displayed typical neuron-like cell morphology and reticular processes. Noggin or Y-27632 alone or in combination induced obviously increased NSE, Nestin, and GFAP levels, which were highest in SHEDs treated with the combination of Noggin and Y-27632. These findings suggest that Y-27632 promotes the proliferation of SHEDs, and Y-27632 and Noggin in combination have a synergistic effect on promoting differentiation of SHEDs into neuron-like cells. | Counterfeit |
Text : Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix‑loop‑helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis‑related markers in human esophageal squamous cell carcinoma TE‑11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively. Following cisplatin treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited expression of the pro‑apoptotic factor Bim and slightly increased the anti‑apoptotic factor Bcl‑xL. However, overexpression of DEC1 during cisplatin treatment failed to affect expression of these markers. Additionally, overexpression of DEC2 improved cell viability and decreased cell apoptosis induced by cisplatin. These results suggested that DEC2 exhibits anti‑apoptotic effects in TE‑11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may therefore have therapeutic potential for the treatment of esophageal cancer, in combination with cisplatin. | Authentic |
Text : Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3 x 10(-4)), Breslow thickness (P=5 x 10(-10)), ulceration (P=9.x10-8) and mitotic rate (P=3 x 10(-7)), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression. | Authentic |
Text : Angiogenesis serves a role in the growth, metastasis and prognosis of tumors. The aim of the present study was to evaluate the angiogenic ability and clinical significance of the immune biomarker soluble interleukin‑2 receptor (sIL‑2R) in gastric cancer (GC) patients. Serum levels of sIL‑2R were measured in 35 GC patients with different stages of disease and 32 healthy individuals, and it was investigated whether the levels were associated with angiogenesis factors, including vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)‑β1. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without recombinant human (rh)sIL‑2R, VEGF and TGF‑β1 for 24 h, and then the HUVECSs were harvested to determine the degree of angiogenesis. The supernatants were also collected for VEGF and TGF‑β1 testing. Serum levels of sIL‑2R were higher in GC patients than in healthy individuals, as were the levels of VEGF and TGF‑β1. In addition, serum levels of sIL‑2R were positively associated with the levels of VEGF and TGF‑β1. Angiogenesis of HUVECs was also increased by rhsIL‑2R pretreatment. VEGF and TGF‑β1 secretion were also incre-ased in supernatants that were pretreated with rhsIL‑2R. The results of the present study suggested that serum levels of sIL‑2R contributes to the pathophysiology of GC progression and may be used as a prognostic biomarker for GC. | Authentic |
Text : The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer. UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments. PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter. Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas. | Authentic |
Text : Gastric cancer (GC) is a deadly disease, and its incidence is especially high in East Asia including China. Recently, some long non-coding RNA (lncRNAs) have been identified as oncogenes or tumor suppressors. This study aimed to determine the function and mechanism of lncRNA LOXL1-AS1 on the progression of GC. RT-PCR was done to measure the expression levels of LOXL1-AS1 and miR-142-5p in GC tissues. The association between pathological indexes and LOXL1-AS1 expression was also analyzed. Human GC cell lines AGS and BGC823 were used as cell models. CCK-8 and colony formation assays were conducted to assess the effect of LOXL1-AS1 on the proliferation of GC cell lines. Transwell assay was conducted to determine the influence of LOXL1-AS1 on cell migration and invasion. Furthermore, luciferase reporter assay was carried out to confirm the relationship of miR-142-5p with LOXL1-AS1. Additionally, Western blot was done to detect the regulatory function of LOXL1-AS1 on PIK3CA, a target of miR-142-5p. In vivo experiment was also performed to validate the roles and mechanism of LOXL1-AS1 on the growth and metastasis of GC cells. LOXL1-AS1 expression in GC samples was significantly increased, which was correlated with unfavorable pathological indexes. Highly expressed LOXL1-AS1 was closely linked to shorter overall survival time and post-progression survival time of the patients. LOXL1-AS1 markedly modulated the malignant phenotypes of GC cells. Additionally, overexpressed LOXL1-AS1 notably reduced the expression of miR-142-5p, but enhanced the expression level of PIK3CA. In vivo experiments further validated that knockdown of LOXL1-AS1 inhibited the growth and metastasis of GC cells via regulating miR-142-5p and PIK3CA. LOXL1-AS1 was a sponge of tumor suppressor miR-142-5p in GC, enhanced the expression of PIK3CA indirectly and functioned as an oncogenic lncRNA. | Authentic |
Text : Multiple myeloma (MM) is a hematological malignancy that lacks a cure. However, novel combination therapy is a current anti-MM strategy. Doxorubicin (DOX) is a type of anthracycline which is a first-line chemotherapeutic for treating MM and induces senescence in many types of cancer. Dinaciclib is a potent, small molecule CDK inhibitor with promise for treating several types of cancer in I/II phase clinical trials. In the present study the anticancer effects and underlying mechanisms of dinaciclib combined with DOX in MM RPMI-8226 cells were investigated. Results indicated that DOX induced cell viability inhibition, cell cycle arrest and senescence. Furthermore, DOX resulted in increased alterations in DNA damage-related proteins such as p-ATM, p-Chk2, p-p53, p21 and γH2AX, but not p16. Notably, the combination of dinaciclib and DOX inhibited cell growth and promoted senescence by transforming the suppressive effects of the ATM/Chk2/p53/p21 signaling pathway and enhancing the p16 signaling pathway. Thus, low-dose dinaciclib enhanced anti-MM effects mediated by DOX via transformation of p21-p16 signaling pathways, leading to accelerated senescence, but not apoptosis. The present findings suggest this approach may be a promising therapeutic strategy for the treatment of MM. | Authentic |
Text : Objective: Many studies have shown that long non-coding RNAs (lncRNAs) are closely related to various cancers. This study aims to explore the roles of lncRNA HOXA11-AS in the development and progression of osteosarcoma (OS). Methods: The expression levels of HOXA11-AS and miR-125a-5p in tumor tissues and the adjacent tissues were detected by RT-PCR method. The proliferation, migration and invasion of MG-63 and KHOS cells were determined. Results: It was found that HOXA11-AS expression levels in OS tissues and OS cell lines were higher than those in OS adjacent tissues and normal human osteoblast cell lines. The higher expression level of HOXA11-AS was positively correlated with more severe clinical stage, distant metastasis and poor prognosis of OS. Inhibition of HOXA11-AS expression could reduce metastasis and invasion of OS cell lines. In addition, HOXA11-AS was found to be an endogenous inhibitor of miR-125a-5p, it down regulated the expression level of miR-125a-5p, and this process could promote the expression of Rab3D, the target gene of miR-125a-5p. Conclusion: Our study elucidated the role of a new HOXA11-AS/miR-125a-5p/Rab3D regulatory pathway in promoting OS metastasis. | Authentic |
Text : Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than it's HPV negative (HPV(-)) counterpart. This may be due to the higher numbers of tumor-infiltrating lymphocytes (TILs) in HPV positive (HPV(+)) tumors. RNA-Sequencing (RNA-Seq) was used to evaluate whether the differences in clinical behaviour simply reflect a numerical difference in TILs or whether there is a fundamental behavioural difference between TILs in these two settings. Thirty-nine HNSCC tumors were scored for TIL density by immunohistochemistry. After the removal of 16 TILlow tumors, RNA-Seq analysis was performed on 23 TILhigh/med tumors (HPV(+) n=10 and HPV(-) n=13). Using EdgeR, differentially expressed genes (DEG) were identified. Immune subset analysis was performed using Functional Analysis of Individual RNA-Seq/ Microarray Expression (FAIME) and immune gene RNA transcript count analysis. In total, 1,634 DEGs were identified, with a dominant immune signature observed in HPV(+) tumors. After normalizing the expression profiles to account for differences in B- and T-cell number, 437 significantly DEGs remained. A B-cell associated signature distinguished HPV(+) from HPV(-) tumors, and included the DEGs CD200, GGA2, ADAM28, STAG3, SPIB, VCAM1, BCL2 and ICOSLG; the immune signal relative to T-cells was qualitatively similar between TILs of both tumor cohorts. Our findings were validated and confirmed in two independent cohorts using TCGA data and tumor-infiltrating B-cells from additional HPV(+) HNSCC patients. A B-cell associated signal segregated tumors relative to HPV status. Our data suggests that the role of B-cells in the adaptive immune response to HPV(+) HNSCC requires re-assessment. | Authentic |
Text : Resistance to anti-androgen therapy in prostate cancer (PCa) is often driven by genetic and epigenetic aberrations in the androgen receptor (AR) and coregulators that maintain androgen signaling activity. We show that specific small RNAs downregulate expression of multiple essential and androgen receptor-coregulatory genes, leading to potent androgen signaling inhibition and PCa cell death. Expression of different short hairpin/small interfering RNAs (sh-/siRNAs) designed to target TMEFF2 preferentially reduce viability of PCa but not benign cells, and growth of murine xenografts. Surprisingly, this effect is independent of TMEFF2 expression. Transcriptomic and sh/siRNA seed sequence studies indicate that expression of these toxic shRNAs lead to downregulation of androgen receptor-coregulatory and essential genes through mRNA 3' UTR sequence complementarity to the seed sequence of the toxic shRNAs. These findings reveal a form of the "death induced by survival gene elimination" mechanism in PCa cells that mainly targets AR signaling, and that we have termed androgen network death induced by survival gene elimination (AN-DISE). Our data suggest that AN-DISE may be a novel therapeutic strategy for PCa. | Authentic |
Text : Tamoxifen treatment is important assistant for estrogen-receptor-positive breast cancer (BRCA) after resection. This study aimed to identify signatures for predicting the prognosis of patients with BRCA after tamoxifen treatment. Data of gene-specific DNA methylation (DM), as well as the corresponding clinical data for the patients with BRCA, were obtained from The Cancer Genome Atlas and followed by systematic bioinformatics analyses. After mapping these DM CPG sites onto genes, we finally obtained 352 relapse-free survival (RFS) associated DM genes, with which 61,776 gene pairs were combined, including 1,614 gene pairs related to RFS. An 11 gene-pair signature was identified to cluster the 189 patients with BRCA into the surgical low-risk group (136 patients) and high-risk group (53 patients). Then, we further identified a tamoxifen-predictive signature that could classify surgical high-risk patients with significant differences on RFS. Combining surgical-only prognostic signature and tamoxifen-predictive signature, patients were clustered into surgical-only low-risk group, tamoxifen nonbenefit group, and tamoxifen benefit group. In conclusion, we identified that the gene pair PDHA2-APRT could serve as a potential prognostic biomarker for patients with BRCA after tamoxifen treatment. | Authentic |
Text : Highly upregulated in liver cancer (HULC) was initially recognized during the screening of a hepatocellular carcinoma (HCC)-specific gene library. Further studies demonstrated its aberrant upregulation in several other tumor types. The oncogenic roles of this long noncoding RNA (lncRNA) have been verified through expression studies as well as functional studies. Moreover, the results of knockdown experiments have indicated diminished carcinogenic effects of cancer cell line in nude mice following HULC silencing. More recent studies have shown that expression levels of this lncRNA might be used as diagnostic biomarkers in cancer patients. Moreover, mechanistical studies have revealed associations between HULC and two HCC-related viruses namely hepatitis B and C viruses. Taken together, HULC can be regarded as a therapeutic target not only for HCC but also for a variety of human malignancies. In the current review, we summarized the recent literature about the role of HULC in the carcinogenesis and its potential application in cancer diagnosis and prognosis. | Authentic |
Text : Objectives: Many studies have examined the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in oral cancer; however, the results are contradictory. We, therefore, conducted a meta-analysis aiming to clarify the prognostic value of the NLR in oral cancer patients. Methods: A literature search was conducted in the PubMed, Web of Science, and Embase databases. Stata version 12.0 was used for statistical analysis. Results: A total of 14 studies with 3216 patients were finally included. The results indicated that a high NLR was significantly associated with worse DFS (n=10, HR = 1.73, 95% confidence interval [CI] = 1.44-2.07, P<0.001). Similar results were observed for overall survival (OS) (n=9, HR = 1.61, 95% CI = 1.39-1.86, P<0.001). Moreover, a high NLR was also correlated with lymph node metastasis (n=7, odds ratio [OR] = 1.62, 95% CI = 1.32-1.98, P<0.001), advanced tumor stage (n=7, OR = 2.63, 95% CI = 2.12-3.25, P<0.001), T stage (n=6, OR = 3.22, 95% CI = 2.59-4.01, P<0.001), tumor differentiation (n=5, OR = 1.48, 95% CI = 1.03-2.11, P=0.033), and perineural invasion (n=4, OR = 1.83, 95% CI = 1.4-2.39, P<0.001). However, an elevated NLR was not correlated with gender. Conclusion: This meta-analysis showed that the NLR might be a potential independent prognostic factor in patients with oral cancer. | Authentic |
Text : Breast cancer, one of the most common health threats to females worldwide, has always been a crucial topic in the medical field. With the rapid development of digital pathology, many scholars have used AI-based systems to classify breast cancer pathological images. However, most existing studies only stayed on the binary classification of breast lesions (normal vs tumor or benign vs malignant), far from meeting the clinical demand. Therefore, we established a multi-class classification system of breast digital pathology images based on AI, which is more clinically practical than the binary classification system. In this paper, we adopted a two-stage architecture based on deep learning method and machine learning method for the multi-class classification (normal tissue, benign lesion, ductal carcinoma in situ, and invasive carcinoma) of breast digital pathological images. The proposed approach achieved an overall accuracy of 86.67% at patch-level. At WSI-level, the overall accuracies of our classification system were 88.16% on validation data and 90.43% on test data. Additionally, we used two public datasets, the BreakHis and BACH, for independent verification. The accuracies our model obtained on these two datasets were comparable to related publications. Furthermore, our model could achieve accuracies of 85.19% on multi-classification and 96.30% on binary classification (non-malignant vs malignant) using pathology images of frozen sections, which was proven to have good generalizability. Then, we used t-SNE for visualization of patch classification efficiency. Finally, we analyzed morphological characteristics of patches learned by the model. The proposed two-stage model could be effectively applied to the multi-class classification task of breast pathology images and could be a very useful tool for assisting pathologists in diagnosing breast cancer. | Authentic |
Text : Bladder cancer (BLCA) is the fifth most common type of cancer worldwide, with high recurrence and progression rates. Although considerable progress has been made in the treatment of BLCA through accurate typing of molecular characteristics, little is known regarding the various genetic and epigenetic changes that have evolved in stem and progenitor cells. To address this issue, we have developed a novel stem cell typing method. Based on six published genomic datasets, we used 26 stem cell gene sets to classify each dataset. Unsupervised and supervised machine learning methods were used to perform the classification. We classified BLCA into three subtypes-high stem cell enrichment (SCE_H), medium stem cell enrichment (SCE_M), and low stem cell enrichment (SCE_L)-based on multiple cross-platform datasets. The stability and reliability of the classification were verified. Compared with the other subtypes, SCE_H had the highest degree of cancer stem cell concentration, highest level of immune cell infiltration, and highest sensitivity not only to predicted anti-PD-1 immunosuppressive therapy but also to conventional chemotherapeutic agents such as cisplatin, sunitinib, and vinblastine; however, this group had the worst prognosis. Comparison of gene set enrichment analysis results for pathway enrichment of various subtypes reveals that the SCE_H subtype activates the important pathways regulating cancer occurrence, development, and even poor prognosis, including epithelial-mesenchymal transition, hypoxia, angiogenesis, KRAS signal upregulation, interleukin 6-mediated JAK-STAT signaling pathway, and inflammatory response. Two identified pairs of transcription factors, GRHL2 and GATA6 and IRF5 and GATA3, possibly have opposite regulatory effects on SCE_H and SCE_L, respectively. The identification of BLCA subtypes based on cancer stem cell gene sets revealed the complex mechanism of carcinogenesis of BLCA and provides a new direction for the diagnosis and treatment of BLCA. | Authentic |
Text : Interleukin (IL)-35 plays an important role in the pathogenesis of rheumatoid arthritis (RA), which is characterized by tumor necrosis factor (TNF)-α activated bone loss beginning early and persisting over time. The aim of this study was to explore the effects and signaling pathway of IL-35 on osteoblasts differentiation in MC3T3E1 cells and TNF-α activated MC3T3E1 cells. A microenvironment was established with low concentration and short-term treatment of TNF-α to mimic inflammatory activated osteoblasts of RA in vitro. The role of IL-35 on osteoblasts proliferation and apoptosis were assessed using cell counting kit (CCK)-8 assay and flow cytometry, respectively. Alkaline phosphatase (ALP) activity was measured by p-nitrophenyl phosphate assay. Extracellular matrix mineralization was measured by Alizarin red S staining. Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in response to IL-35 were investigated using real-time polymerase chain reaction and western blot analysis. Wnt/β-catenin signaling pathway in osteoblasts was investigated. In basal and TNF-α activated osteoblasts, IL-35 promoted proliferation and inhibited apoptosis. Basal and TNF-α activated ALP activity and mineralization in vitro was increased stimulated by IL-35. Furthermore, IL-35 increased the basal and TNF-α activated OPG expression and decreased basal and TNF-α activated RANKL expression. Blocking Wnt/β-catenin signaling pathway with Dickkopf (Dkk)-1 inhibited the osteogenic effects of IL-35. IL-35 stimulates basal and TNF-α activated osteoblasts differentiation through the Wnt/β-catenin signaling pathway, thus highlighting the IL-35 for pharmaceutical and medicinal applications for treating RA bone loss. | Authentic |
Text : The aim of this study was to evaluate the effect of radiofrequency ablation (RFA) on malignant hepatic tumors and compare its therapeutic efficacy in hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). A total of 56 patients with malignant hepatic tumors (34 patients with HCC and 22 patients with MLC) underwent RFA treatment. Two weeks following the RFA treatment, contrast-enhanced abdominal computed tomography scans were used to investigate whether the ablation of the tumors was complete. The patients were followed up for a period ranging from 1 to 93 months, to compare recurrence rates, distant recurrence rates and survival rates. The HCC group exhibited an initial complete ablation rate of 94.1% compared with 95.4% for the MLC group; the difference in ablation rates was not identified to be statistically significant. The recurrence and distant recurrence rates were 14.7% and 11.8%, respectively, for the HCC group and 9.1% and 36.4%, respectively, for the MLC group. The 1-, 3- and 5-year survival rates of the patients with HCC were 86.2, 71.4 and 60.0%, respectively, whereas those for the patients with MLC were 73.9%, 45.4% and 37.5%, respectively. The survival rates of the two groups were identified to be significantly different (P=0.002). RFA treatment was therefore shown to be effective in treating small (<5 cm) malignancies, which is clinically significant. | Authentic |
Text : To explore the protective effect of chemokine ligand 16 (CXCL16) against cell damage induced by oxygen-glucose deprivation (OGD) in human microvascular endothelial cells-1 (HMEC-1) and its possible mechanism. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to determine cell viability and apoptosis of HMEC-1, respectively. qRT-PCR analysis was applied to display the expression of CXCL16 and miR-424. Western blot analysis was used to detect the expression of apoptosis-related proteins, CXCL16, cAMP/PKA/CREB, and PI3K-AKT-GSK3β pathway-related proteins. OGD significantly inhibited cell viability and promoted apoptosis. CXCL16 overexpression decreased the proliferation inhibition and apoptosis of HMEC-1 induced by OGD. Furthermore, we found that CXCL16 was a target of miR-424 and was downregulated by miR-424. The further study showed that overexpression of miR-424 significantly increased proliferation inhibition and apoptosis of HMEC-1 induced by OGD. In addition, we also found that miR-424 was downregulated by PMS2L2. In the subsequence experiment, overexpression of PMS2L2 significantly decreased the proliferation inhibition and apoptosis of HMEC-1 induced by OGD, which suggested that PMS2L2 decreased cell damage of HMEC-1 induced by OGD. Simultaneously, CXCL16 treatment markedly increased the phosphorylation of PKA/CREB and PI3K-AKT-GSK3β and these signal pathways were blocked by signal inhibitors. Our study first demonstrates that oxygen-glucose deprivation (OGD)-induced human microvascular endothelial cells-1 (HMEC-1) cell injury was alleviated by CXCL16 targeted by miR-424 which further targeted by PMS2L2. This process might also be regulated by activating PKA/CREB and PI3K-AKT-GSK3β pathways. | Counterfeit |
Text : Nonsmall cell lung carcinoma (NSCLC) contributes to the highest number of cancer deaths globally. Metastases and chemoresistance are two major confounders to the treatment efficacy in NSCLC. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been associated with high rates of metastases in breast, gastric, and stomach cancers. However, the role of TBL1XR1 in lung cancers remains underexplored. We selected matched and cancerous lung tissues to establish the upregulation of TBL1XR1. Using in vitro assays, we assessed the influence of TBL1XR1 on various cancer phenotypes, namely cell proliferation, chemoresistance, invasion, and metastases in a CRISPR-Cas9-mediated knock out model (A549 cells), and H460 cell lines overexpressing TBL1XR1. We found that TBL1XR1 is overexpressed in NSCLC tissue and patient sera in comparison to paired adjacent normal tissue. Overexpression of TBL1XR1 in NSCLC cell lines mediates cell survival, proliferation, and metastases. TBL1XR1 was found to regulate MEK and Akt pathways through their master regulator c-Met. We observed that activation of c-Met is downregulated in the absence of TBL1XR1. Our study strengthens the contention that TBL1XR1 is a biomarker for prognosis of NSCLC. It may also be considered as an adjunct or core therapeutic target to overcome cisplatin resistance in lung cancers. | Authentic |
Text : Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression. | Authentic |
Text : Long noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. However, the mechanisms by which lncRNAs modulate androgen-independent prostate cancer (AIPC) development remain largely unknown. Next-generation sequencing technology and RT-qPCR were used to assess LEF1-AS1 expression level in AIPC tissues and adjacent normal tissues. Functional in vitro experiments, including colony formation, EDU and transwell assays were performed to assess the role of LEF1-AS1 in AIPC. Xenograft assays were conducted to assess the effect of LEF1-AS1 on cell proliferation in vivo. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) assays were performed to elucidate the regulatory network of LEF1-AS1. The next-generation sequencing results showed that LEF1-AS1 is significantly overexpressed in AIPC. Furthermore, our RT-qPCR assay data showed that LEF1-AS1 is overexpressed in AIPC tissues. Functional experiments showed that LEF1-AS1 promotes the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and tumour growth in vivo by recruiting the transcription factor C-myb to the promoter of FZD2, inducing its transcription. Furthermore, LEF1-AS1 was shown to function as a competing endogenous RNA (ceRNA) that sponges miR-328 to activate CD44. In summary, the results of our present study revealed that LEF1-AS1 acts as a tumour promoter in the progression of AIPC. Furthermore, the results revealed that LEF1-AS1 functions as a ceRNA and regulates Wnt/β-catenin pathway activity via FZD2 and CD44. Our results provide new insights into the mechanism that links the function of LEF1-AS1 with AIPC and suggests that LEF1-AS1 may serve as a novel potential target for the improvement of AIPC therapy. | Authentic |
Text : Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and is also involved in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here we investigated the role of miR-147 in the regulation of the stem cell-like traits of colon cancer cells. We observed that miR-147 was downregulated in several colon cancer cell lines, and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2, and NANOG in the colon cancer cell lines HCT116 and SW480. Overexpressed miR-147 inhibited EMT by increasing the expression of epithelial markers E-cadherin and α-catenin while decreasing the expression of mesenchymal markers fibronectin and vimentin. Moreover, activation of EMT by TGF-β1 treatment significantly counteracted the inhibitive effect of miR-147 on the expression of CSC markers OCT4, SOX2, and NANOG, supporting the idea that overexpressing miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that overexpressed miR-147 downregulated the expression of β-catenin, c-myc, and survivin, which were related to the Wnt/β-catenin pathway. Moreover, treatment of miR-147 mimic-transfected cells with the Wnt/β-catenin pathway activator LiCl attenuated the inhibitive effect of the miR-147 mimic on the EMT and stem cell-like traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon cancer cells by suppressing EMT via the Wnt/β-catenin pathway. In summary, our present study highlighted the crucial role of miR-147 in the inhibition of the stem cell-like traits of colon cancer cells and indicated that miR-147 could be a promising therapeutic target for colon cancer treatment. | Counterfeit |
Text : Colon cancer-associated transcript 2 (CCAT2), a novel lncRNA has been reported as an oncogene in several cancers. This study was aimed to explore whether CCAT2 also exerted oncogenic roles in endometrial cancer cells. The expression of CCAT2 in 30 pairs of endometrial cancer and matched non-cancerous tissues were detected by qRT-PCR. Two endometrial cancer cell lines HEC-1-A and RL95-2 were used throughout this study. CCAT2 in cells was silenced by transfection with shRNA targeted CCAT2, then cell growth and metastasis were assessed by performing trypan blue staining, Transwell assay, and flow cytometry. Dual-luciferase reporter assay was used to detect the combination of miR-216b and CCAT2. Besides, the expression of miR-216b and Bcl-2 in cells were overexpressed or suppressed by transfection with their correspondingly mimic/vector or inhibitor/shRNA. qRT-PCR and western blot analysis were performed to detect the expression of Bcl-2 and main factors in PTEN/PI3K/AKT and mTOR signaling pathways. CCAT2 was highly expressed in endometrial cancer tissues when compared to non-cancerous endometrial tissues. Knockdown of CCAT2 inhibited HEC-1-A and RL95-2 cells viability, migration, invasion, but induced apoptosis. CCAT2 was an endogenous sponge by competing for miR-216b, and miR-216b suppression alleviated CCAT2 silence-diminished cell growth and metastasis. miR-216b negatively regulated Bcl-2 and Bcl-2 could further active PTEN/PI3K/AKT and mTOR signaling pathways. To conclude, these results demonstrated lncRNA CCAT2 was highly expressed in endometrial cancer tissues. Knockdown of CCAT2 inhibited cell growth and metastasis of endometrial cancer cells by sponging miR-216b. | Counterfeit |
Text : Hepatocyte cell adhesion molecule (hepaCAM), a new type of CAM, belongs to the immunoglobulin superfamily. Recently, hepaCAM was reported to be implicated in cancer development, and many researchers investigated its biological function in the tumorigenesis of various cancers. However, what kind of role hepaCAM plays in colorectal cancer (CRC) remains unknown. In this study, we found that hepaCAM was downregulated in CRC tissues and cell lines. Overexpression of hepaCAM inhibited CRC cell proliferation, migration, and invasion in vitro. Furthermore, the tumorigenesis assay showed that increased expression of hepaCAM suppressed CRC tumor growth and metastasis in vivo. We also demonstrated that overexpression of hepaCAM reduced the protein expression levels of β-catenin, cyclin D1, and c-Myc, indicating its inhibitory effect on the Wnt/β-catenin signaling pathway. In conclusion, our study results suggest hepaCAM as a promising therapeutic target for CRC and provide a better understanding for the molecular basis of CRC progression. | Authentic |
Text : From the heartwood of Dalbergia parviflora, eight new compounds, khrinones A (1), B (2), C (3), D (4), and E (5), isodarparvinol B (6), dalparvin (7), and (3S)-sativanone (22), along with 32 known compounds, have been isolated and characterized as 17 isoflavones, nine isoflavanones, five flavanones, six isoflavans, and three miscellaneous substances. Isolates were evaluated for their cell proliferation stimulatory activity against the MCF-7 and T47D human breast cancer cell lines, and their luciferase inductive effects using luciferase transiently transfected MCF-7/luc and T47D/luc cells were also determined. Isoflavones such as genistein (10), biochanin A (11), tectorigenin (12), and 2'-methoxyformononetin (13) stimulated the proliferation of both cells, and concentrations of lower than 1 muM of these compounds showed equivalent activity to 10 pM of estradiol (E2). The new isoflavanone (22) also showed activity against both cell types, although it was weaker than that of the corresponding isoflavone (2'-methoxyformononetin, 13). Two optically active isoflavanones (22 and 24: (3S)-violanone) stimulated the proliferation of both cell lines at lower concentrations than three racemates (21: vestitone, 23: 7,3'-dihydroxy-4'-methoxyisoflavanone, and 25: 3-O-methylviolanone). Bowdichione (20), an isoflavone with a quinone structure in its B-ring, showed activity against only one cell line associated with MCF-7 in these assays. | Authentic |
Text : Mesenchymal-epithelial transition factor (c-Met) is the only high affinity receptor for hepatocyte growth factor (HGF), and is frequently activated in many human cancers. However, little is known about the role of the HGF/c-Met signaling pathway in the progression of human oral squamous cell carcinoma (OSCC). This study evaluated the role of the HGF/c-Met signaling pathway in the progression of human OSCC. We found that the expression of c-Met was significantly increased in human OSCC tissues than in normal mucosa adjacent to the tumor (P<0.05), but was not correlated with clinicopathological parameters. Additionally, the selective c-Met inhibitor JNJ was found to inhibit cell viability and migration and promote apoptosis in OSCC cell lines, and also blocked the activation AKT, ERK1/2, and NF-κB p65; thus, suggesting that HGF/c-Met signaling may play an important role in the tumorigenic properties of OSCC cells via the AKT, ERK1/2, and NF-κB pathways. Collectively, these results indicated that HGF/c-Met signaling may serve essential roles in the progression of human OSCC, and may thus be a basis for the development of novel therapeutic approaches in the treatment of OSCC. | Authentic |
Text : Angiogenesis is known as one of the hallmarks of cancer. Multiple lines evidence indicated that vascular endothelium growth factor (VEGF) is a key player in the progression of angiogenesis and exerts its functions via interaction with tyrosine kinase receptors (TKRs). These receptors could trigger a variety of cascades that lead to the supply of oxygen and nutrients to tumor cells and survival of these cells. With respect to pivotal role of angiogenesis in the tumor growth and survival, finding new therapeutic approaches via targeting angiogenesis could open a new horizon in cancer therapy. Among various types of therapeutic strategies, nanotechnology has emerged as new approach for the treatment of various cancers. Nanoparticles (NPs) could be used as effective tools for targeting a variety of therapeutic agents. According to in vitro and in vivo studies, NPs are efficient in depriving tumor cells from nutrients and oxygen by inhibiting angiogenesis. However, the utilization of NPs are associated with a variety of limitations. It seems that new approaches such as NPs conjugated with hydrogels could overcome to some limitations. In the present review, we summarize various mechanisms involved in angiogenesis, common anti-angiogenesis strategies, and application of NPs for targeting angiogenesis in various cancers. | Authentic |
Text : This study explored the systematic evaluation and meta-analysis of different concentrations of PCP on the risk of long-term bradycardia in fetuses. Cochrane Library, Embase, PubMed, China Biomedical Literature Service, CNCNKI, and Wanfang database were computerized to collect all case-control studies on the association between variety classes and different concentrations of environmental pollutant gas to fetal of prolonged bradycardia. After evaluating the quality of the inclusion study and extracting valid data, meta-analysis was performed using Stata15 software. Relative hazards were calculated using the Mantel-Haenszel method and the random effect model, and P values and I 2 values were used for heterogeneity evaluation. When heterogeneity occurs, subgroup analysis and sensitivity analysis were used to explore the sources. A total of 15 studies were included, including 1202 patients with fetal of prolonged bradycardia and 1380 in the control population. Meta-analysis showed that there was no statistical difference in PCP < 0.1 mg/L between the experimental group and control group (OR = 1.03, 95% CI (0.62, 1.72), P=0.90, I 2 = 0%, Z = 0.13), but there was a statistical difference in PCP > 5 mg/L (OR = 1.73, 95% CI (1.15, 2.58), P=0.008, I 2 = 0%, Z = 2.65), PCP > 10 mg/L (OR = 1.75, 95% CI (1.19, 2.57), P=0.004, I 2 = 14%, Z = 2.85), and PCP >15 mg/L (OR = 2.02, 95% CI (1.38, 2.95), P=0.0003, I 2 = 77%, Z = 3.61). In this study, we found that different concentrations of PCP increased the risk of long-term bradycardia in fetuses, and the risk coefficient increased with the increase of PCP concentration. | Counterfeit |
Text : Aberrant macrophage infiltration and activation has been implicated in gastric inflammation and carcinogenesis. Overexpression of Wnt5a and downregulation of SFRP5, a Wnt5a antagonist, were both observed in gastric cancers recently. This study attempted to explore whether Wnt5a/SFRP5 axis was involved in macrophage chemotaxis and activation. It was found that both Wnt5a transfection and recombinant Wnt5a (rWnt5a) treatment upregulated CCL2 expression in macrophages, involving JNK and NFκB signals. Conditioned medium from Wnt5a-treated macrophages promoted macrophage chemotaxis mainly dependent on CCL2. SFRP5 from gastric epithelial cells (GECs) inhibited Wnt5a-induced CCL2 expression and macrophage chemotaxis. In addition, Wnt5a treatment stimulated macrophages to produce inflammatory cytokines and COX-2/PGE2, which was also suppressed by SFRP5 from GECs. These results demonstrate that Wnt5a induces macrophage chemotaxis and activation, which can be blocked by GEC-derived SFRP5, suggesting that Wnt5a overproduction and SFRP5 deficiency in gastric mucosa may together play an important role in gastric inflammation and carcinogenesis. | Counterfeit |
Text : Recently, microRNA (miR)-33b has been demonstrated to act as a tumor suppressor in osteosarcoma. However, the regulatory mechanism of miR-33b in osteosarcoma cell proliferation and migration remains largely unknown. In this study, real-time PCR showed that miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Its expression was also decreased in several common osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and migration. HIF-1α was further identified as a target of miR-33b, and its protein levels were reduced after overexpression of miR-33b in U2OS cells. Moreover, overexpression of HIF-1α significantly reversed the suppressive effect of miR-33b on U2OS cell proliferation and migration. In addition, HIF-1α was found to be significantly upregulated in osteosarcoma tissues compared to adjacent nontumor tissues, and their expression levels were inversely correlated to the miR-33b levels in osteosarcoma tissues. According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1α. Therefore, we suggest that the miR-33b/HIF-1α axis may become a promising therapeutic target for osteosarcoma. | Authentic |
Text : The outcomes and safety profiles of neoadjuvant chemotherapy (NACT) + intensity modulated radiotherapy (IMRT) or NACT + IMRT + concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients were retrospectively analyzed. Between 2010 and 2014, 125 patients with stage III-IVb NPC, who were treated with IMRT (36, 28.8%) or IMRT + CCRT (89, 71.2%) following NACT, participated in the research. There were grade 3-4 toxicities during NACT or radiotherapy (RT) in NACT + IMRT group and NACT + IMRT + CCRT group. MRI within 3 months demonstrated that no patient suffered with progressive disease, 116 patients (92.8%) achieved a response rate (RR) with the complete response (CR) rate of 70.4% (88/125) and partial response (PR) rate of 22.4% (28/125), and nine patients (7.2%) showed stable disease (SD) at the primary site and metastatic nodes. Compared with NACT + IMRT group, patients in NACT + IMRT + CCRT group did not show significantly better RR (93.3% vs 91.7%, P=1.00), CR rate (71.9% vs 66.7%, P=0.67), or PR rate (21.4% vs 25%, P=0.81). There was no significant difference in overall survival (OS, P=0.114), local relapse-free survival (LRFS, P=0.124), distant metastasis-free survival (DMFS, P=0.668) or progression-free survival (PFS, P=0.475) between NACT + IMRT group and NACT + IMRT + CCRT group. T classification (P=0.042) and N classification (P=0.021) were independent prognostic factors for DMFS. To sum up, no significant difference was observed in combined RR, CR rate, LRFS, DMFS, PFS, or OS between the two groups. | Authentic |
Text : Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy. | Authentic |
Text : Prostate cancer is one of the most common cancers in men worldwide, second only to lung cancer. The most common method used in diagnosing prostate cancer is the microscopic observation of stained biopsies by a pathologist and the Gleason score of the tissue microarray images. However, scoring prostate cancer tissue microarrays by pathologists using Gleason mode under many tissue microarray images is time-consuming, susceptible to subjective factors between different observers, and has low reproducibility. We have used the two most common technologies, deep learning, and computer vision, in this research, as the development of deep learning and computer vision has made pathology computer-aided diagnosis systems more objective and repeatable. Furthermore, the U-Net network, which is used in our study, is the most extensively used network in medical image segmentation. Unlike the classifiers used in previous studies, a region segmentation model based on an improved U-Net network is proposed in our research, which fuses deep and shallow layers through densely connected blocks. At the same time, the features of each scale are supervised. As an outcome of the research, the network parameters can be reduced, the computational efficiency can be improved, and the method's effectiveness is verified on a fully annotated dataset. | Authentic |
Text : Aerobic glycolysis ('Warburg effect') is used by cancer cells to fuel tumor growth. Interestingly, metastatic melanoma cells rely on glutaminolysis rather than aerobic glycolysis for their bioenergetic needs through the tricarboxylic acid (TCA) cycle. Here, we compared the effects of glucose or glutamine on melanoma cell proliferation, migration and oxidative phosphorylation in vitro. We found that glutamine-driven melanoma cell's aggressive traits positively correlated with increased expression of HIF1α and its pro-autophagic target BNIP3. BNIP3 silencing reduced glutamine-mediated effects on melanoma cell growth, migration and bioenergetics. Hence, BNIP3 is a vital component of the mitochondria quality control required for glutamine-driven melanoma aggressiveness. | Authentic |
Text : Therapy of colorectal cancer (CRC), especially a subset known as locally advanced rectal cancer, is challenged by progression and recurrence. Sphingolipids, a lipid subtype with vital roles in cellular function, play an important role in CRC and impact on therapeutic outcomes. In this review we discuss how dietary sphingolipids or the gut microbiome via alterations in sphingolipids influence CRC carcinogenesis. In addition, we discuss the expression of sphingolipid enzymes in the gastro-intestinal tract, their alterations in CRC, and the implications for therapy responsiveness. Lastly, we highlight some novel therapeutics that target sphingolipid signaling and have potential applications in the treatment of CRC. Understanding how sphingolipid metabolism impacts cell death susceptibility and drug resistance will be critical toward improving therapeutic outcomes. | Authentic |
Text : The advent of Nanotechnology has paved a way for improved disease treatment strategies, the most noteworthy being the mesoporous silica nanoparticles (MSNs) which have gained much recent attention in the field of cancer therapy and its diagnosis. The flaws of the current-day strategies can be overcome by this superior technology through its targeting ability in delivering drugs and image able agents specifically to the tumor sites. MSNs have unique biocompatibility features, its high surface area which contributes in large amount of drug loading and its facility to monitor size and shape of the nanoparticles are few of the positives which makes this technology an enormous asset for the field of Nanotechnology. This review paper is structured in such a way wherein we initially have discussed about the synthesis methods and various functionalization approaches for MSN followed by the different methods used for targeting cancer cells and the latest advances in controlled drug release. Some of the highlights of this review are the biocompatibility of MSNs, in vivo results of MSNs on cancer therapy. This review paper also shortly discuss about combined cancer therapies to overcome the challenges in current-day cancer treatment. Finally, we converge briefly on the recent advancements in the use of hybrid MSNs for obtaining multiple functions. | Authentic |
Text : Salivary gland dysfunction (SGD) induced by chemo- and radiotherapy for head and neck cancer (HNC) has always been a difficult problem in modern medicine. The quality of life of a large number of HNC patients is severely impaired by SGD such as xerostomia and dysphagia. In recent years, several studies have found that acupuncture can improve patients' salivary secretion, but it has not yet been approved as an alternative therapy for SGD. For this reason, we collected the clinical study reports on acupuncture in the treatment of SGD induced by chemo- and radiotherapy in HNC patients in the past 20 years, and analyzed and discussed the advantages and disadvantages of these studies with respect to tumor types, group setting, intervention modality, acupoints selection, outcome evaluation, and safety. We believed that acupuncture is beneficial for SGD, but the existing objective evidence is insufficient to support its effectiveness. Therefore, improving the Standards for Reporting Interventions in Clinical Trials of Acupuncture, selecting the optimal combination of acupoints through scientific and rigorous study design, and exploring the potential mechanism of acupuncture in the treatment of diseases combined with the meridian theory may be effective ways to promote the acceptance of acupuncture as an alternative therapy for SGD in future. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of SGD in future from the perspective of the combination of modern medicine and traditional Chinese medicine. | Authentic |
Text : Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive carcinoma with a poor prognosis. To date, there is no effective treatment for this fatal disease. The manipulation of epigenetic proteins, such as BRD4, has recently emerged as an alternative therapeutic strategy. Our objective was to analyze the effect of BRD4 on the cell progression and chemoresistance of PDAC and the novel mechanisms involved. In the present study, we firstly revealed that the expression of BRD4 was significantly upregulated in PDAC cell lines, compared to that in human pancreatic duct epithelial cells. An in vitro assay showed that the suppression of BRD4 impaired PDAC cell viability and proliferation. Similarly, the tumor growth rate was also decreased in vivo after silencing of BRD4. Furthermore, we showed that the expression of BRD4 was increased after treatment with gemcitabine (GEM). Combination treatment of GEM and BRD4 silencing had a synergistic effect on the chemotherapeutic efficacy in the PANC-1 and MIAPaCa-2 cell lines, and significantly promoted apoptosis. In particular, we demonstrated that BRD4 activated the Sonic hedgehog (Shh) signaling pathway members in a ligand-independent manner in the PDAC cells. Together, our results indicate the important role of BRD4 in PDAC cell proliferation and chemoresistance and suggests that BRD4 is a promising target directed against the transcriptional program of PDAC. | Authentic |
Text : Selaginella moellendorffii Hieron. (SM), a perennial evergreen plant, has been used in the treatment of acute infectious hepatitis, thoracic and hypochondriac lumbar contusions, systemic oedema and thrombocytopaenia. However, the role of a biflavonoid-rich extract from SM (SM-BFRE) in anti-larynx cancer has rarely been reported. In this study, the in vitro and in vivo anti-laryngeal cancer activity and potential mechanisms of SM-BFRE were investigated. An off-line semipreparative liquid chromatography-nuclear magnetic resonance protocol was carried out to determine six biflavonoids from SM-BFRE. In vitro, MTT assay revealed that SM-BFRE inhibited the proliferation of laryngeal carcinoma cells. A wound healing assay indicated that SM-BFRE suppressed the migration of laryngeal cancer cells. Hoechst 33 258 and Annexin V-FITC/PI double staining assays were performed and verified that SM-BFRE induced apoptosis in laryngeal carcinoma cells. The Hep-2 bearing nude mouse model confirmed that SM-BFRE also exhibited anticancer effect in vivo. In addition, Western blot analysis demonstrated that SM-BFRE exerted its anti-laryngeal cancer effect by activating the mitochondrial apoptotic pathway and inhibiting STAT3 and Akt/NF-κB signalling pathways. All results suggested that SM-BFRE could be considered as a potential chemotherapeutic drug for laryngeal cancer. | Authentic |
Text : To observe the promotion effect of Yiqi Yangxue decoction combined with chemotherapy on the rapid recovery of non-small cell lung cancer (NSCLC) patients after surgery. Eighty postoperative NSCLC patients admitted to our hospital from April 2019 to September 2021 were divided into a chemotherapy group (n = 40) and a traditional Chinese medicine (TCM) group (n = 40) according to a random sampling method. Both groups were treated with surgery and postoperative routine chemotherapy. The TCM group was treated with Yiqi Yangxue decoction, one dose per day, starting from the first day of chemotherapy. Four weeks was a course of treatment, and three courses of treatment were taken continuously. The levels of serum tumour markers (carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), carbohydrate antigen 125 (CA-125)), immune function indicators (CD3+, CD4+/CD8+, and NK cells), Pittsburgh Sleep Quality Index (PSQI) score, and Insomnia Severity Index (ISI) were compared between the two groups before and after treatment, and the clinical efficacy of the two groups was assessed with reference to the WHO efficacy criteria for solid tumours, and the toxic side effects of the two groups were assessed with reference to the WHO classification criteria for the toxic effects of chemotherapeutic drugs. After treatment, the levels of CEA, CYFRA21-1, and CA-125 were lower than those before treatment in both groups, and they were lower in the TCM group than in the chemotherapy group (P < 0.05). After treatment, the levels of CD3+, CD4+/CD8+, and NK cells in both groups were higher than before treatment, and they were higher in the TCM group than in the chemotherapy group (P < 0.05). After treatment, the PSQI and ISI scores of both the groups were lower than those before treatment, and they were higher in the TCM group than in the chemotherapy group (P < 0.05). After treatment, the overall tumour control rate was higher in the TCM group than in the chemotherapy group (P < 0.05). During the treatment period, the TCM group showed lower levels of gastrointestinal reactions, leucopenia, anaemia, and neurotoxicity than the chemotherapy group (P < 0.05). The combination of Yiqi Yangxue decoction combined with chemotherapy for postoperative NSCLC patients can effectively reduce serum tumour marker levels, enhance the body's immune function and sleep quality, and the patient's efficacy and toxicity reduction are obvious, which is conducive to the rapid recovery of many indicators after surgery. | Authentic |
Text : MicroRNAs (miRNA/miRs) are small, non-coding RNA molecules (19-25 nucleotides in length), which function to regulate gene expression. It has been reported that miR-128 serves an important role in regulating cancer cell growth; increasing evidence has indicated that the expression of miR-128 is decreased in pancreatic cancer (PC) cells. However, the specific mechanisms of miR-128 in regulating PC cell growth are unclear. In the present study, it was confirmed that the expression of miR-128 was significantly decreased within PC tissues compared with adjacent normal tissues via reverse transcription-quantitative polymerase chain reaction analysis. In addition, miR-128 mimics inhibited PC MIA-PaCa2 cell growth by enhancing cell apoptosis in a caspase-dependent manner. Furthermore, the results of the present study demonstrated that double minute 4 (MDM4) may be a direct target for miR-128 via a dual luciferase report assay; miR-128 may inhibit MDM4 expression, and increase p53 and cleaved caspase-3 protein expression levels. In summary, the present study indicated that miR-128 is downregulated in PC, and it may be a promising target for future PC diagnosis and treatment. | Authentic |
Text : With the consideration of the dynamic role of microRNAs (miRNAs) in breast cancer, miRNAs may serve as therapeutic targets, helping to prevent development of therapy resistance, maintain stable disease, and prohibit metastatic spread. We identified the differentially expressed breast cancer-related gene ribonucleotide reductase subunit M2 (RRM2) as the study focus through microarray expression profiles. Next, the upstream regulatory microRNA (miR)-4500 of RRM2 was predicted using bioinformatics website analysis, and their binding was verified by a dual luciferase reporter gene assay. The regulatory effects of miR-4500 on breast cancer cell proliferation, apoptosis, migration, invasion, and capillary-like tube formation of endothelial cells were assessed by gain- and loss-of-function experiments. The experimental data revealed that miR-4500 was downregulated, whereas RRM2 was upregulated in breast cancer cells. Mechanistic analysis revealed that miR-4500 downregulated the RRM2 expression to inactivate the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, miR-4500 exerted anti-tumor effects by targeting RRM2 through suppression of the MAPK signaling pathway in vitro, evidenced by attenuated cancer cell migration and invasion and capillary-like tube formation of endothelial cells. The in vivo experiments further corroborated in vitro results. Collectively, overexpressed miR-4500 could downregulate RRM2 and inhibit activation of the MAPK signaling pathway, thus attenuating breast cancer cell proliferation, invasion, migration, and angiogenesis and promoting breast cancer cell apoptosis. | Authentic |
Text : Background: Cancer-associated fibroblasts (CAFs) are mainly involved in cancer progression and treatment failure. However, the specific signature of CAFs and their related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Here, methods to recognize gene signatures were employed to roughly assess the infiltration of CAFs in RCC, based on the data from The Cancer Genome Atlas (TCGA). Weighted Gene Coexpression Network Analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify the gene signature. Single-cell and cell line sequencing data were used to verify the expression specificity of the gene signature in CAFs. The gene signature was used to evaluate the infiltration of CAFs in each sample, and the clinical significance of each key gene in the gene signature and CAFs was analyzed. We observed that the CAF infiltration was higher in kidney cancer and advanced tumor stage and grade than in normal tissues. The seven key genes of the CAF gene signature identified using WGCNA showed high expression of CAF-related characteristics in the cell clustering landscape and fibroblast cell lines; these genes were found to be associated with extracellular matrix function, collagen synthesis, cell surface interaction, and adhesion. The high CAF infiltration and the key genes were verified from the TCGA and Gene Expression Omnibus data related to the advanced grade, advanced stage, and poor prognosis of RCC. In summary, our findings indicate that the clinically significant gene signature may serve as a potential biomarker of CAFs in RCC, and the infiltration of CAFs is associated with the pathological grade, stage, and prognosis of RCC. | Authentic |
Text : Skin cancer is, at present, the most common type of malignancy in the Caucasian population. Its incidence has increased rapidly in the last decade for both melanoma and non-melanoma skin cancer. Differential expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers, including skin cancers. Since miRNAs' discovery as regulators of gene expression, their importance grew in the field of oncology. miRNAs can post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness. Nowadays, these short regulatory RNAs are perceived as one of the epigenetic markers for the identification of new diagnostic and/or prognostic molecular markers. Moreover, as miRNAs can drive tumorigenesis, they might eventually represent new therapy targets. Some miRNAs are pleiotropic, such as miR-214, which was found deregulated in several other tumors besides skin cancers. Some others are specific for one or more skin cancer types, like miR-21 and miR-221 for cutaneous melanoma and cutaneous squamous carcinoma or miR-155 for melanoma and cutaneous lymphoma. The goal of this review was to summarize some of the main miRNA detection technologies that are used to evaluate miRNAs in tissues and body fluids. Furthermore, their quantification limits, conformity, and robustness are discussed. Aberrant miRNA expression is analyzed for cutaneous melanoma, cutaneous squamous cell carcinoma (CSCC), skin lymphomas, cutaneous lymphoma, and Merkel cell carcinoma (MCC). In this type of disease, miRNAs are described as potential biomarkers to diagnose early lesion and/or early metastatic disease. In the future, whether in tissue or circulating in body fluids, miRNAs will gain their place in skin cancer diagnosis, prognosis, and future therapeutic targets. | Authentic |
Text : Since demand forecasting is the first step in managing and operating a tourism business, its accuracy is very important to tourism businesses. In order to address NN's drawbacks, such as local optimization, slow convergence, and large sample sizes, this paper organically combines the PSO and NN models and builds a PSO-NN-based tourism demand forecasting model. The tourism demand forecasting indexes, the choice of NN forecasting models, the modelling process, and the implementation methods are first analysed and studied along with the fundamental theories and forecasting techniques of PSO and NN. In order to increase the precision of the prediction model, the PSO algorithm is also used to optimise the weights and thresholds of the NN. The final section of the paper compares the performance of the model developed in this paper with the most widely used model for forecasting tourism demand. According to the experimental findings, this model's prediction accuracy can reach 95.81 percent, or about 10.09 percent higher than the prediction accuracy of the conventional NN model. There are some practical implications to this research. Applying the optimization model to the forecast of tourism demand is doable and practical. | Counterfeit |
Text : Multiple studies have found that microRNAs (miRNAs) are involved in the development of cerebral ischemia. MiR-579-3p can inhibit inflammatory responses and apoptosis, leading to ischemia/reperfusion (I/R) damage. However, the mechanism of how miR-579-3p actions in brain I/R injury remains unclear. This study aimed to investigate the mechanism of the role of miR-579-3p in brain I/R injury. A rat model of cerebral ischemia-reperfusion injury was established by suture method. The effects of miR-579-3p on cerebral infarction size, brain water content, and neurological symptoms were evaluated. Flow cytometry was used to detect apoptosis. ELISA was used to detect the level of inflammatory factors. Western blot was used to detect the expression of P65, NCOA1, Bcl-2 and Bax. The relationship between miR-579-3p and NCOA1 was analyzed by bioinformatics analysis and luciferase assay. Overexpression of miR-579-3p reduced infarct volume, brain water content and neurological deficits. Overexpression of miR-579-3p inhibited the expression level of the inflammatory cytokines, such as TNF-α, IL-6, COX-2 and iNOS, and increased the expression level of IL-10. MiR-579-3p overexpression inhibited NF-кB activity by reducing NRIP1. In addition, miR-579-3p could reduce the apoptotic rate of cortical neurons. Overexpression of miR-579-3p inhibited the activity of caspase-3, increased the expression level of anti-apoptotic gene Bcl-2 in neurons, and decreased the expression level of apoptotic gene Bax. miR-579-3p can be used to treat brain I/R injury, and its neuroprotective effect may be ascribed to the reduction of inflammation and apoptosis. | Counterfeit |
Text : Noise-induced hearing loss (NIHL) is one of the most frequent disabilities in industrialized countries. Evidence shows that hair cell loss in the auditory end organ is responsible for the majority of various ear pathological conditions. The functional roles of the receptor tyrosine kinase ROR1 have been underscored in various tumours. In this study, we evaluated the ability of ROR1 to influence cochlear hair cell loss of guinea pigs with NIHL. The NIHL model was developed in guinea pigs, with subsequent measurement of the auditory brainstem response (ABR). Gain-of-function experiments were employed to explore the role of ROR1 in NIHL. The interaction between ROR1 and Wnt5a and their functions in the cochlear hair cell loss were further analysed in response to alteration of ROR1 and Wnt5a. Guinea pigs with NIHL demonstrated elevated ABR threshold and down-regulated ROR1, Wnt5a and NF-κB p65. The up-regulation of ROR1 was shown to decrease the cochlear hair cell loss and the expression of pro-apoptotic gene (Bax, p53) in guinea pig cochlea, but promoted the expression of anti-apoptotic gene (Bcl-2) and the fluorescence intensity of cleaved-caspase-3. ROR1 interacted with Wnt5a to activate the NF-κB signalling pathway through inducing phosphorylation and translocation of p65. Furthermore, Wnt5a overexpression decreased the cochlear hair cell loss. Collectively, this study suggested the protection of overexpression of ROR1 against cochlear hair cell loss in guinea pigs with NIHL via the Wnt5a-dependent NF-κB signalling pathway. | Counterfeit |
Text : Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3' untranslated region (3'UTR) at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2)-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3' UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3' UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT) and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development. | Authentic |
Text : Pirin (PIR) protein belongs to the superfamily of cupin and is highly conserved between eukaryotic and prokaryotic organisms. It has been reported that PIR is upregulated in various tumors and involved in tumorigenesis. However, its biological functions particularly in promoting tumorigenesis are, to date, poorly characterized. Here we report that knockdown of PIR in MCF7 and MDA-MB-231 cell lines causes a dramatic decrease in cell proliferation and xenograft tumor growth in mice. Mechanistically, the cell cycle activator E2F1 and its target genes cdk4, cdk6, cycE, cycD and DDR1 are remarkably downregulated in PIR depleted cells, leading to G1/S phase arrest. Luciferase reporter assay and chromatin immunoprecipitation assay indicate that PIR can activate E2F1 transcription by binding to its promoter region. Consistent with the observation in PIR knockdown cells, PIR inhibitors markedly inhibit the proliferation of both cell lines. Furthermore, knockdown of PIR significantly decreases the abilities of MCF7 cells for mobility and invasion in vitro and their metastasis in mice, which may be attributed to the decrease of DDR1. In conclusion, PIR stimulates tumorigenesis and progression by activating E2F1 and its target genes. Our finding thus suggests PIR as a potential druggable target for the therapy of cancers with high expression level of PIR. | Authentic |
Text : Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-xL, and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-xL overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their receptors (EPO-R, VEGFR-2), and SCD-1 in early stages of ccRCC. | Authentic |
Text : N7-methylguanosine modification-related lncRNAs (m7G-related lncRNAs) are involved in progression of many diseases. This study was aimed at revealing the risk correlation between N7-methylguanosine modification-related lncRNAs and survival prognosis of oral squamous cell carcinoma. In the present study, coexpression network analysis and univariate Cox analysis were used to obtained 31 m7G-related mRNAs and 399 m7G-related lncRNAs. And the prognostic risk score model of OSCC patients was evaluated and optimized through cross-validation. Through the coexpression analysis and risk assessment analysis of m7G-related prognostic mRNAs and lncRNAs, it was found that six m7G-related prognostic lncRNAs (AC005332.6, AC010894.1, AC068831.5, AL035446.1, AL513550.1, and HHLA3) were high-risk lncRNAs. Three m7G-related prognostic lncRNAs (AC007114.1, HEIH, and LINC02541) were protective lncRNAs. Then, survival curves were drawn by comparing the survival differences between patients with high and low expression of each m7G-related prognostic lncRNA in the prognostic risk score model. Further, risk curves, scatter plots, and heat maps were drawn by comparing the survival differences between high-risk and low-risk OSCC patients in the prognostic model. Finally, forest maps and the ROC curve were generated to verify the predictive power of the prognostic risk score model. Our results will help to find early and accurate prognostic risk markers for OSCC, which could be used for early prediction and early clinical intervention of survival, prognosis, and disease risk of OSCC patients in the future. | Authentic |
Text : Cancer progression is strictly dependent on the relationship between tumor cells and the surrounding stroma, which supports cancer malignancy promoting several crucial steps of tumor progression, including the execution of the epithelial to mesenchymal transition (EMT) associated with enhancement in cell invasion, resistance to both anoikis and chemotherapeutic treatments. Recently it has been highlighted the central role of microRNAs (miRNAs) as regulators of tumor progression. Notably, in several tumors a strong deregulation of miRNAs is observed, supporting proliferation, invasion, and metabolic reprogramming of tumor cells. Here we demonstrated that cancer-associated fibroblasts induce a downregulation of miR-1247 in prostate cancer (PCa) cells. We proved that miR-1247 repression is functional for the achievement of EMT and increased cell invasion as well as stemness traits. These phenomena contribute to promote the metastatic potential of PCa cells as demonstrated by increased lung colonization in in vivo experiments. Moreover, as a consequence of miR-1247 downregulation, we observed a correlated increased expression level of neuropilin-1, a miR-1247 target involved as a coreceptor in the epidermal growth factor receptor signaling. Taken together, our data highlight miR-1247 as a potential target for molecular therapies aimed to block the progression and diffusion of PCa. | Authentic |
Text : Malignant lymphoma of the uterine cervix is exceedingly rare and is difficult to diagnose by cervical cytology. The current study presents a case of malignant lymphoma of the uterine cervix that was presumptively diagnosed by cervical cancer screening in which the patient had no clinical symptoms. The anterior lip of the uterine cervix was occupied by a macroscopic hemorrhagic tumor. The obtained tumor cells exhibited typical cytological features of malignant lymphoma and were positive for CD20. The final diagnosis was diffuse large B cell lymphoma of the uterine cervix, stage IIEA (Ann Arbor classification). The patient received 6 courses of R-CHOP chemotherapy and achieved complete remission. Despite its rarity, the possibility of malignant lymphoma should be considered while screening for cervical cancers using Pap smears. The Pap test screening may be useful for the early diagnosis of malignant lymphoma of the uterine cervix in certain cases. By reaching a rapid and accurate diagnosis, immediate treatment may be initiated and surgery may be avoided. | Authentic |
Text : Gastrointestinal cancers are among the most prevalent cancers in the general population. Despite effective early diagnostics and intervention, the gastrointestinal cancer-related mortality still remains elevated. Berberine (BBR) is a benzyl tetra isoquinoline alkaloid exracted from several plants. BBR is nontoxic to human normal cells, but suppresses the growth of different tumor cells: melanoma, epidermoid carcinoma, hepatoma, oral carcinoma, glioblastoma, prostatic carcinoma, and gastric carcinoma. In particular, BBR seems to suppress the proliferation of gastrointestinal cancers in a number of preclinical models. Several mechanisms of action have been hypothesized and demonstrated: immunomodulation, inhibition of topoisomerase enzymes, suppression of the EGF receptor, Her2/neu, and the VEGF receptor, induction of p53, Cip1/p21, Kip1/p27, Rb expression, induction of apoptosis (by regulation of MMPs pathway, caspases, Bax, and Smac/DIABLO), inhibition of arylamin N-acetyltransferase activity, and regulation of microRNAs expression. The aim of this review is to summarize the pharmacological effects of BBR on animal and human gastrointestinal cancers. | Authentic |
Text : Betulinic acid (BA), a natural product with a broad range of biological properties, is a lupane-type pentacyclic triterpene isolated from various plants. Evidence is accumulating that BA is cytotoxic against multiple types of human cancer cells; however, its effects on renal carcinoma cells remain obscure. This study aimed to evaluate the anticancer activity of BA in human renal cancer cells in vitro and in vivo. In the current study, we found that BA inhibited renal cancer cell proliferation in a time-dependent and dose-dependent manner in vitro. Moreover, flow cytometry analysis revealed that BA affected the survival of renal cancer cells via the induction of apoptosis. Western blot analysis showed that the occurrence of apoptosis was associated with upregulation of Bcl2-associated X protein and cleaved caspase-3 and downregulation of B-cell lymphoma 2 in renal cancer cells. Additionally, BA treatment augmented the production of reactive oxygen species and induced a significant loss of mitochondrial membrane potential in renal cancer cells, suggesting that BA may trigger apoptosis via the mitochondria-mediated apoptotic pathway. Furthermore, the migrative and invasive capabilities of renal cancer cells were markedly repressed by BA treatment, which was related to upregulation of matrix metalloproteinase (MMP)2, MMP9, and vimentin, and downregulation of tissue inhibitor of metalloproteinase 2 and E-cadherin. Notably, administration of BA retarded tumor growth in 786-O-bearing mice in vivo. Taken together, our results demonstrated the anticancer potential of BA in human renal cancer cells by triggering apoptosis and suppressing migration and invasion. | Authentic |
Text : Mitochondria, a kind of subcellular organelle, play crucial roles in cancer cells as an energy source and as a generator of reactive substrates, which concern the generation, proliferation, drug resistance, and other functions of cancer. Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment. Mitochondria have a four-layer structure with a high negative potential, which thereby prevents many molecules from reaching the mitochondria. Luckily, the advances in nanosystems have provided enormous hope to overcome this challenge. These nanosystems include liposomes, nanoparticles, and nanomicelles. Here, we summarize the very latest developments in mitochondria-targeting nanomedicines in cancer treatment as well as focus on designing multifunctional mitochondria-targeting nanosystems based on the latest nanotechnology. | Authentic |
Text : Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which interacts with vascular endothelial growth factor to prevent tumor cell apoptosis and to regulate angiogenesis. However, the precise role of NRP1 in epithelial ovarian carcinoma (EOC) remains to be elucidated. The present study aimed to determine the association between NRP1 and EOC. The expression of NRP1 in ovarian cancer and normal ovarian epithelial tissues was investigated by immunofluorescence, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. The association between the expression of NRP1 with the development of ovarian cancer, clinicopathological characteristics and survival were also analyzed. The results from immunofluorescence, RT-qPCR and western blot analysis demonstrated that NRP1 exhibited significant upregulation in EOC compared with normal ovarian epithelial specimens (P<0.05). The positive expression of NRP1 was higher in cancer tissues at an advanced International Federation of Gynecology and Obstetrics stage, and in cancer tissues with lymph node metastasis and distant metastasis compared with that in cancer tissues without lymph node or distant metastasis (P<0.05). Higher NRP1 expression strongly predicted a shorter survival time (P<0.001). The present findings suggested that increased NRP1 expression may be associated with the development of EOC. Therefore, NRP1 could be used as a valuable prognostic marker as well as a potential molecular therapy target for ovarian cancer patients. | Authentic |
Text : Colon cancer is a detrimental neoplasm of the digestive tract. MicroRNAs (miRNAs) as central regulators have been discovered in colon cancer. Nonetheless, the impact of miR-204-3p on colon cancer remains indistinct. The research attempted to uncover the impacts of miR-204-3p on colon cancer cells growth, migration, and invasion. miR-204-3p expression level in colon cancer tissues and diverse colon cancer cell lines were testified by the quantitative real-time polymerase chain reaction. Exploration of the impacts of miR-204-3p on cell growth, migration, invasion, and their associated factors through assessment of CCK-8, flow cytometry, Transwell, and western blot, respectively. High mobility group AT-hook 2 (HMGA2) expression was then detected in Caco-2 cells after miR-204-3p mimic and inhibitor transfection, additionally dual-luciferase activity was implemented to further uncover the correlation between HMGA2 and miR-204-3p. The impact of HMGA2 on Caco-2 cell growth, migration, and invasion was finally assessed. We found that repression of miR-204-3p was discovered in colon cancer tissues and HCT116, SW480, Caco-2, HT29 and SW620 cell lines. MiR-204-3p overexpression mitigated Coca-2 cell viability, facilitated apoptosis, simultaneously adjusted CyclinD1 and cleaved caspase-3 expression. Cell migration, invasion, and the associated factors were all suppressed by miR-204-3p overexpression. Reduction of HMGA2 was presented in Caco-2 cells with miR-204-3p mimic transfection, and HMGA2 was predicated to be a target gene of miR-204-3p. Besides, HMGA2 silence showed the inhibitory effect on Caco-2 cells growth, migration, and invasion. In conclusion, miR-204-3p repressed colon cancer cell growth, migration, and invasion through targeting HMGA2. | Counterfeit |
Text : The aberrant expression and dysfunction of long non-coding RNAs (lncRNAs) have been identified as critical factors governing the initiation and progression of different human cancers, including diffuse large B-cell lymphoma (DLBCL). LncRNA small nucleolar RNA host gene 16 (SNHG16) has been recognized as a tumour-promoting factor in various types of cancer. However, the biological role of SNHG16 and its underlying mechanism are still unknown in DLBCL. Here we disclosed that SNHG16 was overexpressed in DLBCL tissues and the derived cell lines. SNHG16 knockdown significantly suppressed cell proliferation and cell cycle progression, and it induced apoptosis of DLBCL cells in vitro. Furthermore, silencing of SNHG16 markedly repressed in vivo growth of OCI-LY7 cells. Mechanistically, SNHG16 directly interacted with miR-497-5p by acting as a competing endogenous RNA (ceRNA) and inversely regulated the abundance of miR-497-5p in DLBCL cells. Moreover, the proto-oncogene proviral integration site for Moloney murine leukaemia virus 1 (PIM1) was identified as a novel direct target of miR-497-5p. SNHG16 overexpression rescued miR-497-5p-induced down-regulation of PIM1 in DLBCL cells. Importantly, restoration of PIM1 expression reversed SNHG16 knockdown-induced inhibition of proliferation, G0/G1 phase arrest and apoptosis of OCI-LY7 cells. Our study suggests that the SNHG16/miR-497-5p/PIM1 axis may provide promising therapeutic targets for DLBCL progression. | Authentic |
Text : Antitumor activity of Capsaicin has been studied in various tumor types, but its potency in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. Here, we explored the molecular mechanism of the capsaicin-induced antitumor effects on ESCC Eca109 cells. Eca109 cells were treated with capsaicin in vitro, the migration and invasion capacities were significantly decreased by scratch assay and transwell invasion assay. Meanwhile, matrix metalloproteinase (MMP)-9 (MMP-9) expression levels were also obviously down-regulated by Western blot. However, phosphorylated AMPK levels were significantly up-regulated, and this effect was eliminated by the AMPK inhibitor Compound C treatment. In addition, capsaicin can enhance sirtuin1 (SIRT1) expression, which could activate nuclear factor-κB (NF-κB) through deacetylation, and activate AMPK inducing the phosphorylation of IκBα and nuclear localization of NF-κB p65. Overall, these results revealed that Capsaicin can inhibit the migration and invasion of ESCC cells via the AMPK/NF-κB signaling pathway. | Authentic |