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Text : We investigated the relationship between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) in children and adolescents. We carried out a retrospective study of thyroidectomies performed from 2004 to 2017 at The First People's Hospital and the Tumor Hospital of Yunnan Province (Kunming, China). The occurrence and features of PTC and benign thyroid disease (BTD) in children and adolescents (age ≤ 20 years) were compared. We evaluated 258 consecutive thyroidectomies. Among children and adolescents with PTC, 23 cases were histopathologically confirmed as HT. Mean tumor diameter was smaller in children and adolescents with PTC than in those with BTD. Thyroid-stimulating hormone (TSH) level was abnormally elevated in a greater proportion of children and adolescents with PTC as compared to those with BTD or youths with PTC. The proportion of thyroglobulin antibody (TGAb)- and thyroid peroxidase antibody (TpoAb)-positive children and adolescents was higher in the PTC than in the BTD group. Among children and adolescents with PTC, 23 had HT as compared to two in the BTD group. The proportion of children/adolescents with abnormally elevated TSH levels was higher for the PTC combined with HT group than for the PTC without HT group. A multivariate conditional logistic regression analysis showed that elevated TGAb was an independent risk factor for PTC in children and adolescents. HT is associated with an increased occurrence of PTC in children and adolescents. | Authentic |
Text : The aim of this study is to investigate the role of mircoRNA-200c-3p (miR-200c-3p) on hippocampal neuron injury in epileptic rats through the regulation of the AKT signaling pathway by targeting RECK. The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were injected with miR-200c-3p inhibitors, inhibitors NC, siRNA-negative control (NC) and RECK-siRNA. The astrocyte activation, levels of oxidative stress indexes, contents of inflammatory factors and the AKT signaling pathway-related proteins in hippocampus tissues were evaluated. High expression of miR-200c-3p and low expression of RECK were found in the hippocampus tissues of epileptic rats. Downregulation of miR-200c-3p or upregulation of RECK decreased apoptosis of hippocampal neurons, expression of GFAP, content of MDA and increased the activities of GSH-Px and SOD, decreased expression of TNF-α, IL-1β and IL-6 as well as expression of p-PI3K/t-PI3K and p-Akt/t-Akt in hippocampus tissues of epileptic rats. Our study provides evidence that downregulation of miR-200c-3p reduces damage of hippocampal neurons in epileptic rats by upregulating RECK and inactivating the AKT signaling pathway. | Counterfeit |
Text : Purpose: Numerous microRNAs (miRNAs) are aberrantly expressed in breast cancer, and the dysregulation of miRNAs may affect the aggressiveness of this cancer. Aberrant expression of miRNA-937 (miR-937) in gastric and lung cancers has been reported, which plays tumor-suppressive or oncogenic roles in carcinogenesis including cancer progression. Our purpose was to investigate the involvement of miR-937 in breast cancer progression. Patients and methods: The expression profile of miR-937 in breast cancer was assessed by reverse-transcription quantitative PCR. Biological effects of miR-937 upregulation on the malignant characteristics of breast cancer cells were determined in a series of functional experiments. The direct target of miR-937 in breast cancer cells was also identified. Results: Herein, the expression levels of miR-937 were notably lower in breast cancer, and its underexpression was significantly correlated with lymph node metastasis and TNM stage. Patients with breast cancer underexpressing miR-937 showed shorter overall survival than did patients with breast cancer overexpressing miR-937. Proliferation, migration, and invasiveness of breast cancer cells were evidently suppressed by miR-937 upregulation. In addition, ectopic miR-937 expression hindered breast cancer tumor growth in vivo. Forkhead box Q1 (FOXQ1) mRNA was found to be a direct target of miR-937 in breast cancer. FOXQ1 turned out to be overexpressed in breast cancer tissues, and its overexpression negatively correlated with miR-937 expression. Moreover, silencing of FOXQ1 recapitulated the tumor-suppressive effects of miR-937 overexpression on breast cancer cells. Notably, FOXQ1 restoration abrogated the miR-937-mediated suppression of proliferation, migration, and invasiveness of breast cancer cells. Conclusion: These results collectively revealed that miR-937 acts as a tumor suppressor in breast cancer and restrains cancer progression by directly targeting FOXQ1 mRNA. These data suggest that targeting of the novel miR-937-FOXQ1 axis is an attractive therapeutic method against breast cancer. | Counterfeit |
Text : Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology. | Authentic |
Text : Nanomagnetic devices, such as nano-field effect transistor biosensors and radio frequency magnetic induction therapies, came into being with the development of medical nanomaterials. The application of nanomagnetic materials in the treatment of cancers is rapidly becoming increasingly important because of its ability to target therapy and diagnose early. In this review, an untechnical overview of the fundamental of magnetism in nanomaterials and an illustration of how these materials are applied are presented. The applications of nano-field effect transistor biosensors for the detection of tumor biomarker nanomaterials in the therapy and diagnosis of cancers and nanomagnetic materials are summarized in this paper. A systemic summary of the use of nanomagnetic materials and nano-filed effect transistor biosensors for the treatment and diagnosis of tumors is also provided in the review. | Authentic |
Text : Ginsenoside Rg3, a bioactive constituent isolated from Panax ginseng, exhibits antitumorigenic, antioxidative, antiangiogenic, neuroprotective and other biological activities are associated with the regulation of multiple genes. DNA methylation patterns, particularly those in the promoter region, affect gene expression, and DNA methylation is catalyzed by DNA methylases. However, whether ginsenoside Rg3 affects DNA methylation is unknown. High performance liquid chromatography assay, MspI/HpaII polymerase chain reaction (PCR) and reverse transcription‑quantitative PCR were performed to assess DNA methylation. It was demonstrated that 20(S)‑ginsenoside Rg3 treatment resulted in increased inhibition of cell growth, compared with treatment with 20(R)‑ginsenoside Rg3 in the human HepG2 hepatocarcinoma cell line. It was additionally revealed that treatment with 20(S)‑ginsenoside Rg3 reduced global genomic DNA methylation, altered cystosine methylation of the promoter regions of P53, B cell lymphoma 2 and vascular endothelial growth factor, and downregulated the expression of DNA methyltransferase (DNMT) 3a and DNMT3b more than treatment with 20(R)‑ginsenoside Rg3 in HepG2 cells. These results revealed that the modulation of DNA methylation may be important in the pharmaceutical activities of ginsenoside Rg3. | Authentic |
Text : MicroRNAs (miRNAs) have been demonstrated to be critical in regulating tumor development and progression. The present study investigated the expression of miR‑588 using reverse transcription‑quantitative polymerase chain reaction analysis in 85 cases of lung squamous cell carcinoma (SCC), and observed the correlation between the expression of miR‑588 with clinical pathologic features. The results indicated that the expression of miR‑588 was predominantly lower in the tumor samples, compared with non‑tumorous samples, and was negatively associated with tumor stages and lymph node invasion. The present study also examined the significance of the expression of miR‑588 in SCC using gain‑ and loss‑of‑function analyses. It was found that miR‑588 inhibited tumor cell migration and invasion. In addition, it was revealed that the overexpression of miR‑588 in SCC cells reduced the mRNA and protein levels of progranulin (GRN), whereas miR‑588 silencing increased the expression of GRN. A luciferase activity assay showed that miR‑588 was able to directly bind to the 3'untranslated region of GRN and regulate its expression. Furthermore, it was found that the expression of GRN was inversely correlated with the expression of miR‑588 in 85 paired SCC samples. These results indicated that GRN was involved in the miR-588-mediated suppressive functions in the progression of SCC. | Authentic |
Text : INhibitor of Growth protein 4 (ING4) is a potential chromatin modifier that has been implicated in several cancer-related processes. However, the role of ING4 in prostate cancer (PC) is largely unknown. This study aimed to assess ING4's role in global transcriptional regulation in PC cells to identify potential cellular processes associated with ING4 loss. RNA-Seq using next-generation sequencing (NGS) was used to identify altered genes in LNCaP PC cells following ING4 depletion. Ingenuity pathways analysis (IPA®) was applied to the data to highlight candidates, ING4-regulated pathways, networks and cellular processes. Selected genes were validated using RT-qPCR. RNA-Seq of LNCaP cells revealed a total of 159 differentially expressed genes (fold change ≥ 1.5 or ≤ - 1.5, FDR ≤ 0.05) following ING4 knockdown. RT-qPCR used to validate the expression level of selected genes was in agreement with RNA-Seq results. Key genes, unique pathways, and biological networks were identified using IPA® analysis. This is the first report of global gene regulation in PC cells by ING4. The resultant differential expression profile revealed the potential role of ING4 in PC pathogenesis possibly through modulation of key genes, pathways and biological networks that are central drivers of the disease. Collectively, these findings shed light on a novel transcriptional regulator of PC that ultimately may influence the disease progression and as a potential target in the disease therapy. | Authentic |
Text : The exfoliation of exfoliative cells from gastric serosa into the peritoneum is the main cause of peritoneal metastasis, which is the most common form of postoperative recurrence in gastric cancer. This study investigates the effects of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) on the biological properties of gastric cancer cells. mRNA expression of VEGF and EGF in gastric cancer tissues from 80 patients suffering from serosa-infiltrated gastric cancer (T3) was examined. The differences of proliferation, movement, adhesion and invasion among 4 gastric cancer cell lines were analysed. The mRNA expression of EGF, EGFR, VEGF and VEGFR in the gastric cancer cell lines was examined before and after adding endostatin (Endostar) or cetuximab (Erbitux) to observe changes of gastric cancer cells. mRNA levels of EGF and VEGF in positive exfoliative cytology cases were significantly higher than negative cases (p < 0.05). The biological properties were reduced sequentially in MGC803, HGC27, BGC823 and SGC7901 (p < 0.05). The mRNA expression of EGF, EGFR, VEGF and VEGFR was the strongest in MGC803, but was attenuated significantly after treatment (p < 0.05). Lower survival was related to positive exfoliative cytology, lymphatic node metastasis, serosa-infiltrated and poorly differentiated gastric cancer. The expression of VEGF and EGF was correlated with the properties of gastric cancer cells. Specific inhibition of VEGF and EGF may impair the biological properties of gastric cancer cells in vitro. | Counterfeit |
Text : Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding protein with multiple cellular functions, including intracellular Ca2+ homeostasis, oxidative stress responses, and lectin binding. CRT can also modulate cell adhesion, cell-cell interactions, migration, phagocytosis, integrin-dependent Ca2+ signaling, and immune responses, and plays an important role in cellular proliferation, differentiation, and apoptosis. Given these roles, it is not surprising that CRT function has important implications in health and disease. Considerable evidence in recent years suggests that CRT dysfunction is associated with cancer and that CRT could be a diagnostic marker and a target for cancer therapy. These topics are discussed in depth in this review. | Authentic |
Text : To investigate the expression of KI-67 and LEF-1 in patients after breast cancer resection and its effects on patients' prognosis. A total of 89 breast cancer patients admitted to the first affiliated Hospital of Shantou University Medical College from January 2010 to February 2013 were enrolled as the study group, and 76 healthy individuals were enrolled as the control group. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of KI-67 and LEF-1 in the serum. The relationship of the two indexes and clinicopathological data of the breast cancer patients were analyzed. In addition, the diagnostic value of KI-67 and LEF-1 in breast cancer patients was analyzed by receiver operating characteristic (ROC) curves, and their diagnostic value in the postoperative 5-year recurrence was also analyzed. Furthermore, the expression of KI-67 and LEF-1 in patients with postoperative recurrent breast cancer within 5 years was evaluated. The expression of KI-67 and LEF-1 in the study group was higher than in the control group (p<0.05), and the expression of KI-67 and LEF-1 was significantly related to the tumor size and lymph node metastasis (both p<0.05). ROC curve showed that the area under the curve (AUC) of the diagnostic value of KI-67 and LEF-1 for breast cancer patients was 0.860 and 0.858 respectively, and that of the diagnostic value KI-67 combined with LEF-1 for breast cancer patients was 0.924. In addition, the AUC of the diagnostic value of KI-67 and LEF-1 for the recurrence of breast cancer within 5 years was 0.699 and 0.651, respectively, and that of diagnostic value of KI-67 combined with LEF-1 for the recurrence of breast cancer within 5 years was 0.758. The expression of KI-67 and LEF-1 in patients with recurrent disease within 5 years after operation was higher than in patients without recurrence. The expression of KI-67 and LEF-1 in breast cancer patients is significantly higher than in healthy individuals, which has certain diagnostic value in breast cancer. The expression of the two indexes is related to tumor size and lymph node metastasis, and the survival of patients with high expression of KI-67 and LEF-1 is worse. | Authentic |
Text : Dietary phytochemicals and diet types (e.g., the Mediterranean diet) have been shown to have anti-cancer properties. However, the effects of combined treatment with dietary phytochemicals and different diet types on primary and metastatic tumor growth have yet to be investigated. The purpose of this study is to investigate the effects of phytochemicals combined with diet types on breast cancer metastasis. The inhibitory effects on breast cancer metastasis of three phytochemicals (allicin, hesperidin, astragalus polysaccharides) and two diet types (Mediterranean diet, restricted diet), separately or in combination, were evaluated based on: (i) detection of circulating tumor cells (CTCs) using an in vivo capture method; and (ii) primary tumor growth. All dietary factors significantly inhibited the growth of primary tumors and metastases, with combinations showing enhancing the effects. Dietary phytochemicals and diet types should be further evaluated as adjunct therapies and lifestyle modifications in cancer patients. Furthermore, the in vivo CTC capture method allows dynamic monitoring of cancer metastasis over time, providing a useful approach to evaluating treatment effects in real-time. | Authentic |
Text : MicroRNA-1294 (miR-1294) was reported to act as a tumor suppressor in several cancers. However, the biological function of miR-1294 in osteosarcoma (OS) has not been investigated. We, therefore, investigated the clinical significance and underlying mechanisms of miR-1294 in OS. Quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the levels of miR-1294. Targets of miR-1294 were validated by luciferase reporter assay and Western blot. In vitro functional assays were performed to investigate the effects of miR-217 on cell proliferation and invasion. We found miR-1294 was downregulated in OS tissues and cell lines. Downregulation of miR-1294 has a significant negative impact on the overall survival of OS patients. Overexpression of miR-1294 suppresses OS cell proliferation and invasion in vitro. Then, luciferase reporter assay validated Homeobox A9 (HOXA9) was a downstream target of miR-1294. Expression patterns of miR-1294 were inversely correlated with HOXA9 in OS tissues, strengthening the findings from the luciferase reporter assay. Further functional assays revealed that overexpression of HOXA9 could reverse the inhibition effects of miR-1294 on cell proliferation and invasion. These results suggested miR-1294 functions as a tumor suppressor in OS progression by targeting HOXA9. | Authentic |
Text : This study was designed to investigate the expression level of circRNA_100876 in breast cancer (BC) tissues or cells, and to further explore whether it can promote cell metastasis and proliferative capacity via targeting microRNA- 361-3 p. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of circRNA_100876 in 50 pairs of BC tissue specimens and corresponding adjacent ones, and the correlation between circRNA_100876 expression and prognosis of patients with BC was analyzed. Meanwhile, qRT-PCR was further performed to verify circRNA_100876 level in BC cell lines. In addition, circRNA_100876 knockdown model was constructed using lentivirus and transfected in BC cells. Subsequently, the impact of circRNA_100876 on BC cell function was analyzed using Cell Counting Kit-8 (CCK-8), transwell and clone formation assays. The interplay between circRNA_100876 and microRNA- 361-3 p was verified using the Luciferase reporter gene assay and cell reverse experiment. QRT-PCR results showed that circRNA_100876 level in BC tissues was conspicuously higher than that in the adjacent tissues, and the patients with distant metastasis had higher expression than those without. Moreover, patients with a high expression of circRNA_100876 had a relatively lower overall survival rate. Compared with the NC group, the cell proliferation and invasion ability of circRNA_100876 knockdown group was conspicuously decreased. QRT-PCR revealed that microRNA-361-3p and circRNA_100876 showed a negative correlation in the expression level of genes in BC tissues. In addition, the results of the Luciferase reporter gene assay confirmed that circRNA_100876 can be targeted by microRNA-361-3p through their binding site. High expression of circRNA_100876 is conspicuously positively relevant to poor prognosis of BC patients. Additionally, circRNA_100876 is able to promote BC metastasis as well as proliferative capacity by modulating microRNA-361-3p expression. | Authentic |
Text : Background: The dysregulation of microRNAs has been implicated in the progression of different malignancies. Herein, we sought to identify the precise roles of miR-155-5p in the progression of cervical cancer. Materials and methods: The expressions of miR-155-5p in cervical carcinoma cells and clinical tissues were assessed using qRT-PCR analysis. The functions of miR-155-5p on the growth of cervical cancer cell were investigated using MTT and colony formation. The Transwell and wound closure assays were selected to explore the influence of miR-155-5p on the invasion and migration of cervical cancer cell. The effect of miR-155-5p on cervical carcinoma cell growth and metastasis in vivo was investigated using xenograft model and experimental lung metastasis model. Bioinformatics analysis and luciferase reporter assay were applied to identify that tumor protein p53-inducible nuclear protein 1 (TP53INP1) was the target of miR-155-5p. Results: MiR-155-5p was significantly upregulated in cervical cancer tissue than that in control normal tissue. Downexpression of miR-155-5p decreased the growth, migration as well as invasiveness abilities of cervical cancer cell in vitro whereas overregulation of miR-155-5p caused the opposite outcomes. In addition, the in vivo mice xenograft model suggested that downexpression of miR-155-5p restrained the progression of cervical cancer cell whereas overexpression of miR-155-5p caused opposite outcomes. Furthermore, we revealed that TP53INP1 was the target of miR-155-5p and the level of TP53INP1 was inversely associated with miR-155-5p level in cervical carcinoma. Furthermore, TP53INP1 knockdown mimicked the influence of miR-155-5p on cervical cancer proliferation, migration and invasion phenotypes. Finally, overexpression of TP53INP1 impaired the promote effect of miR-155-5p on cervical cancer cell and downregulation of TP53INP1 counteracted the suppressive impact of miR-155-5p on the aggressiveness of cervical cancer cell. Conclusion: Our study indicated that miR-155-5p regulated the development of cervical cancer cell by regulating the expression of TP53INP1. | Authentic |
Text : Bladder cancer (BC) is the most common of those affecting the urinary tract, and a significant proportion of the cases are attributable to tobacco use as well as occupational and environmental factors. The aim of this study is to estimate the current incidence of BC in an industrialized area in northeastern Spain and to analyze its time trends over three decades from an ecological perspective. Patients diagnosed with histologically confirmed primary BC, during 2018-2019, in an area in northeastern Spain (430,883 inhabitants) were included. Crude and age-standardized incidence rates were estimated per 100,000 person-years based on the number of individuals getting their first diagnosis. An exploratory time trend analysis was carried out to describe the evolution in tobacco use and occupational or environmental risk factors and the incidence of BC in the same area from the 1990s. 295 patients were included (age 72.5 ± 10.3 years; 89.8% men). The crude rate was 62.6 (95% CI: 51.9-73.2) for men and 6.8 (95% CI: 3.4-10.3) for women. The annual rate adjusted to the European Standard Population was 85.3 (95% CI:75.0-95.5) for men and 7.0 (95% CI:4.5-9.5) for women. From 1994 to 2018, the prevalence of smokers decreased in men (42.3% to 30.9%) as well as in the active population working in the industry (44.36% to 22.59%). Nevertheless, the car fleet, especially diesel, has increased considerably. The annual mean concentrations of air (PM10, PM2.5, O3, and NO2) and water (nitrates, arsenic, trihalomethanes) pollutants were within the regulatory limit values, but not the maximum levels. The incidence of BC is one of the highest in men but not in women, despite the decrease in tobacco use and industrial activity (perhaps related to high latency after carcinogen exposure cessation) and despite the control of environmental pollution (the maximum regulatory limit probably needs to be lowered). Finally, a similar exposure to the carcinogen would result in a gender-specific differential incidence. | Authentic |
Text : Colorectal cancer (CRC) is a common disease with high mortality and morbidity. Annexin A3 (ANXA3) belongs to the structurally homologous family of Ca2+ and phospholipid-binding proteins. This study aimed to investigate the effects and potential mechanisms of ANXA3 on oxaliplatin (Ox) resistance in CRC. We generated two human CRC cell lines (HCT116/Ox and SW480/Ox) with acquired Ox resistance and determined their resistance properties. ANXA3 expression and cell apoptosis, migration and invasion also were evaluated. We found that cell viability of HCT116/Ox and SW480/Ox was higher than that in parental cells in the presence of Ox. ANXA3 was highly expressed in HCT116/Ox and SW480/Ox cells. ANXA3 downregulation diminished cell survival, migration and invasion, while increased the apoptosis of HCT116 and SW480 with or without Ox. Moreover, depletion of ANXA3 reduced cell viability and BrdU incorporation, increased cell apoptosis and c-caspase 3 expression in HCT116/Ox with or without Ox. A transwell assay determined that knockdown of ANXA3 impeded the migration and invasion of HCT116/Ox and SW480/Ox cells. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) decreased upon ANXA3 depletion in HCT116/Ox cells, and ANXA3 silencing suppressed Ox-induced activation of ERK and JNK signaling pathway. ANXA3 downregulation reduced Ox resistance in CRC, and treatment with the ERK inhibitor PD098059 or JNK inhibitor SP600125 contributed to this process. These results indicate that silencing ANXA3 could overcome Ox resistance in CRC via the mitogen-activated protein kinase signaling pathway. | Authentic |
Text : With the accelerated pace of life in modern society, changes in work style, and the popularity of computers, the prevalence of cervical spondylosis (CSR) is increasing, and the age of onset is advancing. Once suffering from this disease, it is often difficult to cure and recurring, with complex clinical symptoms, causing a serious impact on human health. To evaluate the efficacy of manipulation and cervical traction in the treatment of radical cervical spondylosis. The PubMed, CNKI, and Wanfang databases were searched for literature. The literature related to this study was included according to selective criteria and inhibitory elimination criteria, and valuable information was selected for statistical analysis, resulting in a total of 11 randomized controlled trials with 994 subjects. The short-term efficacy of manual treatment for CSR was superior to that of cervical traction alone (P < 0.05); subgroup analysis showed that the short-term efficacy of pulling or rotational manipulation was superior to that of cervical traction (P < 0.05). The mean difference between symptoms and manipulation VAS scores was higher before and after treatment when compared with cervical traction for CSR (P < 0.05); the subgroup analysis showed that VAS scores, upper extremity anesthesia scores, and survivorship scores were lower for pulling or rotating manipulation than for cervical traction (P < 0.05). The advantages of manual therapy in terms of short-term efficacy, VAS pain scores, neck pain, upper extremity anesthesia, and survivorship improvement provide a theoretical basis for its clinical impact. | Counterfeit |
Text : Therapeutic strategies targeting both cancer cells and associated cells in the tumor microenvironment offer significant promise in cancer therapy. We previously reported that generation 5 (G5) dendrimers conjugated with cyclic-RGD peptides target cells expressing integrin alpha V beta 3. In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5-FI-RGD-rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit mTOR signaling and VEGF expression. In addition, G5-FI-RGD-rapamycin inhibits mTOR signaling in cancer cells more efficiently under proinflammatory conditions compared to free rapamycin. In vivo studies established that G5-FI-RGD-rapamycin significantly inhibits fibroblast-mediated PCa progression and metastasis. Thus, our results suggest the potential of new rapamycin-conjugated multifunctional nanoparticles for PCa therapy. | Authentic |
Text : The anticancer activity of cationic antimicrobial peptides (AMPs) has become more interesting because some AMPs have selective recognition against cancer cells. However, their antitumor properties and underlying mechanisms in cancer cells have not been clearly understood. In this study, we evaluated the effects of KT2 (lysine/tryptophan-rich AMP) on the cellular uptake and internalization mechanism, cell viability, surface charge of the cell membrane, membrane integrity, apoptotic cell death, and autophagy in human HCT 116 colon cancer cells. We found that KT2 interacted with the cell membrane of HCT 116 cells and was internalized into HCT 116 cells via clathrin-mediated and caveolae-mediated endocytosis mechanisms. The interaction of KT2 with cells caused cell membrane structure change, elevated membrane permeability, and KT2 also affected the lipid component. The results of atomic force microscopy showed cellular membrane defects of KT2-treated cells. The internalized KT2 induced nuclear condensation and apoptotic cell death. It elevated the apoptotic factor levels including those of cytochrome c and apoptosis-inducing factor. Furthermore, KT2 inhibited autophagy by the suppression of autophagy-related 5, autophagy-related 7, autophagy-related 16 like 1, and Beclin-1 proteins. In conclusion, these results revealed the cytotoxicity of cationic KT2 against HCT 116 cells and may help to clarify the interactions between cationic AMPs and cancer cells. | Authentic |
Text : Gastric cancer (GC) is the most widespread type of cancer after lung and liver cancer in men and after breast cancer in women. Thus, the present study was intended to evaluate the effect of ketamine (KET) on gastric cancer cells. The effect of KET was analyzed in vitro by the MTT assay against human gastric cancer cell lines BGC-823, MKN-45 and MKN-28. The effect KET on apoptosis, cell migration and cell cycle arrest was also quantified. Western blot analysis was performed to estimate the effect of KET on apoptosis mediators and PI3K/AKT/mTOR pathway mediators. A mouse xenograft assay was also conducted to further confirm the anticancer activity. KET causes reduction of cellular viability of BGC-823, MKN-45 and MKN-28, with a more significant effect against BGC-823 cells. The KET treatment showed a dose-dependent increase in apoptotic cells among BGC-823 cells. KET causes a significant dose-dependent decline in migration of treated cells. It causes induction of apoptosis mediated via the mitochondrial pathway, where it causes a decline in Bcl2 and mitochondrial cytochrome c level together with increase in expression of Bax, cytosolic cytochrome c and cytosolic apoptotic protease activating factor-1 (Apaf-1). The level of p-PI3K, p-mTOR, p-GSK3β and p-AKT was found to be downregulated in a dose-dependent manner in KET-treated cells. In a mouse xenograft model, KET causes a reduction in relative tumour volume and tumour weight. Our results suggest that ketamine has the ability to inhibit progression of gastric cancer via induction of apoptosis and attenuation of PI3K/Akt/mTOR. | Authentic |
Text : Tumor numerical models have been used to quantify solute transport with a single capillary embedded in an infinite tumor expanse, but measurements from different mammalian tumors suggest that a tissue containing a single capillary with an infinite intercapillary distance assumption is not physiological. The present study aims to investigate the limits of the intercapillary distance within which nanoparticle transport resembles solute extravasation in a breast tumor model as a function of the solute size, the intercapillary separation, and the flow direction in microvessels. Solute transport is modeled in a breast tumor for different vascular configurations using mixture theory. A comparison of a single capillary configuration (SBC) with two parallel cylindrical blood vessels (2 BC) and a lymph vessel parallel to a blood vessel (BC_LC) embedded in the tissue cylinder is performed for five solute molecular weights between 0.1 kDa and 70 kDa. The effects of counter flow (CN) versus co-current flow (CO) on the solute accumulation were also investigated and the scaling of solute accumulation-decay time and concentration was explored. We found that the presence of a second capillary reduces the extravascular concentration compared to a single capillary and this reduction is enhanced by the presence of a lymph vessel. Varying the intercapillary distance with respect to vessel diameter shows a deviation of 10-30% concentration for 2 BC and 45-60% concentration for BC_LC configuration compared to the reference SBC configuration. Finally, we introduce a non-dimensional time scale that captures the concentration as a function of the transport and geometric parameters. We find that the peak solute concentration in the tissue space occurs at a non-dimensional time, T peak ∗ = 0.027 ± 0.018, irrespective of the solute size, tissue architecture, and microvessel flow direction. This work suggests that the knowledge of such a unique non-dimensional time would allow estimation of the time window at which solute concentration in tissue peaks. Hence this can aid in the design of future therapeutic efficacy studies as an example for triggering drug release or laser excitation in the case of photothermal therapies. | Authentic |
Text : Glioblastoma multiforme (GBM, WHO grade IV astrocytoma) has become a public health burden worldwide. Alpinumisoflavone (AIF) is a flavonoid compound isolated from Derris eriocarpa. This study aims to examine the role of AIF in GBM. Our results showed that AIF could decrease the cell viability of both T98G and U373 GBM cell lines. AIF treatment also caused cell cycle arrest at G1/G0 phase along with upregulation of p27 and downregulation of cyclin D1. AIF could significantly induce apoptosis in GBM cells. Activation of caspase-9, disruption of mitochondrial membrane potential and loss of mitochondrial cytochrome C were also observed following AIF treatment. Inhibition of glycolysis by AIF was demonstrated by reducing glucose consumption and lactate output in GBM cells. Moreover, HK2 was identified as the molecular target responsible for the anticancer activities of AIF against GBM cells. The results showed that HK2 knockdown enhanced the anticancer activities of AIF whereas ectopic HK2 expression compromised its effect. Furthermore, the antineoplastic activities of AIF in vivo were also validated in xenograft murine model. Our results showed that AIF can exhibit anticancer activities in GBM by promoting apoptosis and inhibiting glycolysis via targeting HK2. | Authentic |
Text : Cancer patients face multiple challenges, such as infertility caused by exposure to gonadotoxic agents and gonadal irradiation during cancer treatment. Little is known about the health practitioners' knowledge and practice regarding fertility preservation and its available options in Saudi Arabia. Thus, this study is designed to evaluate the level of knowledge, attitude, and practice (KAP) towards fertility preservation in cancer patients among health practitioners in an environmental region in Saudi Arabia. The cross-sectional study was carried out between September 2020 and January 2021. A self-administered questionnaire was distributed among health practitioners from a variety of specialties who work closely with cancer patients. Out of 100 participants, 90% need more knowledge about fertility preservation. The lack of fertility preservation clinics in the patient's area and its unaffordable expenses significantly influenced the health practitioners' attitude towards fertility preservation discussion with cancer patients. The results revealed that 92% of the participants agreed that the Saudi Ministry of Health should establish practice guidelines and provide fertility preservation services for cancer patients. The present study showed that clinical practitioners' knowledge remains insufficient. Education of health practitioners and the establishment of practice guidelines and fertility preservation clinics for cancer patients are required. | Authentic |
Text : Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer-related circRNA. Nevertheless, its clinical relevance, functional roles, and mechanism have not been studied in PDAC. In the current study, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of circ_0007534 in 60-paired PDAC tissue samples and different cell lines. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. An animal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via a Bcl-2/caspase-3 pathway. The xenograft study further confirmed the cell growth promoting the role of circ_0007534. Mechanistically, miR-625 and miR-892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR-625 and miR-892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC. | Authentic |
Text : Pancreatic cancer (PC) remains a major health concern, with conventional cancer treatments exerting little influence on the disease course. MicroRNA-520b (miR-520b) functions as a tumor suppressor in several types of human cancers, whereas its anti-tumor property in the context of PC is still fundamental. The aim of this study is to identify the potential therapeutic role of miR-520b, transferred by exosomes, derived from normal fibroblasts (NFs) in PC progression. A gain-of-function study was performed to examine the roles of miR-520b in PC cell line SW1990, which suggested that miR-520b served as a tumor suppressor in PC. In order to confirm the role of exosomal miR-520b, exosomes were isolated from NF culture medium and cocultured with SW1990 cells. During the coculture experiments, we disrupted exosome secretion and upregulated exosomal miR-520b. The in vitro coculture studies revealed that miR-520b was transferred from NF-derived exosomes to PC cells and thereby suppressed PC cell proliferation, invasion, migration, and stimulated apoptosis. Furthermore, inhibited tumor growth and live metastasis upon elevated miR-520b in exosomes were observed in vivo. Conjointly, our study demonstrates that NF-derived exosomal miR-520b impedes the progression of PC, which contributes to a novel, therapeutic role of exosomal miR-520b for treating PC. | Counterfeit |
Text : Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications. This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis. Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer. Trial Registry: NTR5947 - date of registration: 1 August 2016. | Authentic |
Text : Small cell lung cancer (SCLC) is sensitive to first-line chemotherapy and radiotherapy, but frequently recurs. Temozolomide is a chemotherapeutic drug suitable for the treatment of relapsed SCLC, particularly when brain metastases are present. The response of SCLC to temozolomide may be associated with the methylation status of O6-methyl-guanine-DNA methyltransferase (MGMT). Isocitrate dehydrogenase (IDH) mutation is an independent prognostic factor of good outcome in gliomas and appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. In order to identify the status of MGMT promoter methylation and IDH1/2 mutation of SCLC in China, 33 SCLC specimens from patients that underwent surgery were retrospectively collected in Zhejiang Cancer Hospital (Hangzhou, China) between 2008 and 2014. High-resolution melting analysis and methylation-specific polymerase chain reaction were used to detect MGMT promoter methylation, and polymerase chain reaction amplification and Sanger sequencing were utilized to detect IDH1/2 mutation. Of the 33 examined SCLC specimens, MGMT promoter methylation was detected in 17 patients (51.5%), and no IDH1/2 mutations were detected in the analyzed samples. These findings indicate that the IDH1/2 mutation may not be an ideal marker in SCLC patients treated with temozolomide. Future studies on the predictive and prognostic value of MGMT promoter methylation are urgently required for patients with relapsed SCLC treated with temozolomide in China. | Authentic |
Text : Gastric cancer peritoneal metastasis has high mortality. At present, there is no effective way to cure the patients diagnosed with gastric cancer peritoneal metastasis due to its indistinct molecular mechanism. Therefore, to understand the pathogenesis and help for further target therapy, we conduct comprehensive analysis of peritoneal metastasis by bioinformatics in gastric cancer. Microarray sequencing was used to find differential mRNAs and long non-coding RNAs (lncRNAs) expression between primary foci and peritoneal metastases lesion in gastric cancer. RT-qPCR was used to verify the expression levels of lncRNAs in gastric cancer cells after co-culture with adipocytes. TCGA, Cytoscape, lnCAR, cBioPoratal and R packages (ggrisk, survival, survminer, timeROC, forestplot, immunedeconv, ggplot2, pheatmap and ggpubr) were applied in this work. Adipocytes co-culture model was used to mimic the peritoneal microenvironment and found that LINC01151 (NR_126348), FAM27B (NR_027422) and LINC00924 (NR_027133) were up-regulated in co-culture group. Increased LINC00924 expression was significantly associated with reduced overall survival and up-regulated percentage abundance of tumor-infiltrating CD8+ T, B, macrophage and NK immune cells; moreover, immune checkpoint blockers (ICBs) had a worse effect on the LINC00924 high expression group. Furthermore, through univariate and multivariate Cox regression analysis, we found that LINC00924-related PEX5L in CNC network was an independent prognostic factor in gastric cancer progression. LINC00924 expression was associated with poor survival, immune infiltrations and worse response to ICBs. LINC00924 might be immunotherapeutic targets of advanced gastric cancer. | Authentic |
Text : Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection. | Authentic |
Text : Axillary web syndrome (AWS) is a complication of surgical procedures in breast cancer (BC) patients. This condition with poorly understood incidence and etiology is characterized by the locoregional development of scar tissue, leading to subcutaneous cording, motion impairment and pain. The early identification of patients at risk for AWS would improve their clinical management. Here, we sought to characterize the prevalence of and the risk factors associated with AWS in BC women after surgery. All patients with BC that underwent axillary surgery referred to an Outpatient Service for Oncological Rehabilitation were retrospectively collected. These women were assessed two weeks after the surgical procedure for their clinicopathologic features, type of therapeutic interventions, and AWS presence, laterality, pain, localization, cords type, and number of cords. Altogether, 177 patients (mean aged 60.65 ± 12.26 years) were included and divided into two groups: AWSPOS (n=52; 29.4%) and AWSNEG (n=125; 70.6%). Patients with tumor N ≥1 (OR=3.7; p<0.001), subjected to mastectomy, axillary lymph node dissection (ALND) and chemotherapy showed significant correlations with AWS onset (p<0.05). The range of shoulder motion limitation (OR=11.2; p<0.001) and the presence of breast cancer related lymphedema (OR=3.5; p=0.020) were associated with AWS. Mastectomy, ALND, chemotherapy, low staging tumors, shoulder range of motion limitations, and BCRL represent risk factors for AWS onset. Realizing new strategies for assessing the individual risk of AWS is a crucial clinical need to improve the health-related quality of life of BC survivors. | Authentic |
Text : To explore the clinical characteristics of metastatic colorectal cancer combined with gastrointestinal perforation and the prognostic value of circulating tumor DNA (ctDNA). A total of 97 patients with metastatic colorectal cancer and gastrointestinal perforation were enrolled as the research objects between February 2016 and January 2019. Their clinicopathological characteristics were statistically analyzed. Patients were divided into the death group (n = 78) and the survival group (n = 19) according to their survival status at 3 years after surgery. The ctDNA level between the two groups was compared. Also, its evaluation value on patient prognosis was analyzed. The survival time in patients with different levels of ctDNA was compared. The clinical staging was stage T4 in patients with metastatic colorectal cancer combined with gastrointestinal perforation, including 70 cases (72.16%) aged ≥60 years and 27 cases (27.84%) <60 years. There were 61 males (62.89%) and 36 females (37.11%). There were 27 cases (27.84%) with primary site at left colon, 59 cases (60.82%) at right colon and 11 cases (11.34%) at rectum. There were 56 cases (57.73%) with number of metastatic organs ≥2 and 41 cases (42.27%) <2. There were 58 cases (59.79%) treated with VEGF inhibitor before perforation, 40 cases (41.24%) with lung metastasis, 72 cases (74.23%) with liver metastasis, 30 cases (30.93%) with pelvic metastasis, 24 cases (24.74%) with distant lymph node metastasis, 56 cases (57.73%) with obstruction, and 35 cases (36.08%) with diverticulum. According to survival status at 3 years after after surgery, patients were divided into the death group (n = 78) and the survival group (n = 19). The level of plasma ctDNA in the death group was higher than that in the survival group (P < 0.05). The area under curve (AUC) of ctDNA for predicting survival of patients was 0.806. According to ctDNA expression, patients were divided into the high expression group (n = 57) and the low expression group (n = 40). The survival rate in the high expression group was lower than that in the low expression group (7.02% (4/57) vs 36.38% (15/40)) (P < 0.001). The median survival time for the two groups was 18.20 and 28.10 months, respectively. Clinical characteristics of metastatic colorectal cancer combined with gastrointestinal perforation include elderly age, obstruction, and diverticulum. The expression of ctDNA has evaluation value for prognosis of patients. | Authentic |
Text : The aqueous extract of red algae was used for bio-inspired manufacturing of cobalt oxide nanoparticles (Co3O4NPs) and for antioxidant, antibacterial, hemolytic potency, and anticancer activity. Typical, characterization techniques include UV-Vis, SEM, EDAX, TEM, FTIR, XRD, and TGA. Using an X-ray diffraction assay, the size of the Co3O4NPs crystal was determined to range from 23.2 to 11.8 nm. Based on TEM and SEM pictures, biosynthesized Co3O4NPs' had a homogeneous spherical morphology with a 28.8 to 7.6 nm average diameter. Furthermore, Co3O4NPs biological properties were investigated, including determining the antibacterial potency using the zone of inhibition (ZOI) method and determining the minimal inhibitory concentration (MIC). The antibacterial activity of Co3O4NPs was higher than that of the ciprofloxacin standard. Alternatively, scavenging of DPPH free radical investigation was carried out to test the antioxidant capacitance of Co3O4NPs, revealing significant antioxidant ability. The biosynthesized Co3O4NPs have a dose-dependent effect on erythrocyte viability, indicating that this technique is harmless. Furthermore, bioinspired Co3O4NPs effectively against HepG2 cancer cells (IC50: 201.3 μg/ml). Co3O4NPs would be a therapeutic aid due to their antioxidant, antibacterial, and anticancer properties. | Authentic |
Text : Recently, the vital role of circular RNAs is discovered in many diseases including tumor progression and metastasis. Hepatocellular carcinoma (HCC) is one of the most ordinary malignant tumors. The purpose of our study is to detect the potential function of hsa_circ_0011946 in HCC to offer new biomarkers and targets. The level of hsa_circ_0011946 in HCC tissues and cell lines was monitored by Real Time Quantitative Polymerase Chain Reaction (RT-qPCR). Pearson's Chi-square test was used to determine the association between hsa_circ_0011946 expression and several clinicopathological factors. Then, hsa_circ_0011946 was knocked down in HCC cells to uncover its function in metastasis of HCC. Cell migrated and invaded ability was measured through transwell assay, Matrigel assay and wound healing assay. Western blot assay was performed to analyze the effect of hsa_circ_0011946 on the epithelial-to-mesenchymal transition (EMT) process. In this research, the expression level of hsa_circ_0011946 was significantly increased in HCC tissues compared to that in adjacent samples. The expression of hsa_circ_0011946 was also increased in HCC cell lines. The hsa_circ_0011946 expression was associated with lymphatic metastasis in HCC patients. Knockdown of hsa_circ_0011946 led to the inhibition of cell migration and invasion in HCC. In addition, results of further experiments revealed that the EMT-related proteins were regulated via the knockdown of hsa_circ_0011946 in HCC. The hsa_circ_0011946 could enhance cell migration and invasion of HCC by inducing the EMT process. | Authentic |
Text : Colorectal cancer (CRC) is one of the most leading causes of cancer deaths worldwide. In the study, we aimed to identify key long non-coding RNAs (lncRNAs) significantly associated with prognosis of CRC and develop an expression-based lncRNA signature to provide survival risk prediction for CRC patients. LncRNA expression profiles and clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Six hundred and eighteen differentially expressed lncRNAs were identified between CRC and normal tissues. After univariate and multivariate Cox regression analysis for these differentially expressed lncRNAs and overall survival of CRC patients, six predictive lncRNAs (RP1-170O19.17, RP11-785D18.3, RP11-798K3.2, XXbac-B476C20.9, RP11-481J13.1, and RP11-167H9.4) were finally screened out to construct a six-lncRNA signature, based on which patients in the training dataset were divided into the high-risk and low-risk group with significantly different overall survival. ROC curve analysis demonstrated competitive performance of the six-lncRNA signature. The prognostic power of the six-lncRNA signature was successfully validated in the testing and entire dataset. Multivariate Cox regression analysis and stratification analysis further suggested that the six-lncRNA signature was independent of other conventional clinical variables for survival prediction in CRC patients. Functional enrichment analysis revealed the possible roles of these predictive lncRNAs in some cancer-related biological processes and pathways. Our study demonstrated the promising potential of the novel six-lncRNA signature as an independent biomarker for survival prediction of CRC patients. | Authentic |
Text : Claudin-6 (CLDN6), a member of claudin transmembrane protein family, has recently been reported to be undetectable or at low levels in human breast cancer cell lines and tissues and plays a role in suppression of migration and invasion in breast cancer cells. In addition, it is reported that CLDN6 expression is regulated by DNA methylation in various human cancers and cell lines. However, it is unclear how DNA methylation regulates CLDN6 expression. Here we show the mechanism by which DNA methylation regulates CLDN6 expression in human breast cancer cell line MCF-7. RT-PCR, Western blot and immunofluorescent staining were utilized to investigate CLDN6 expression in breast cancer tissues and MCF-7 cells. Methylation-Specific PCR (MSP) was applied to determine DNA methylation status in CLDN6 gene promoter region. Wound-healing assay and invasion assay were utilized to test mobility of MCF-7 cells treated with 5-aza-dC (DNA methyltransferase inhibitor). MeCP2 binding, H3Ac and H4Ac in CLDN6 promoter region were analyzed by ChIP assay. Nuclease accessibility assay was performed for analysis of the chromatin conformation of CLDN6 gene. To study the role of CLDN6 in malignant progression, we used RNAi to knockdown CLDN6 expression in MCF-7 cells treated with 5-aza-dC, and examined the mobility of MCF-7 cells by wound-healing assay and invasion assay. 5-aza-dC and TSA (histone deacetylase inhibitor) application induced CLDN6 expression in MCF-7 cells respectively and synergistically. 5-aza-dC treatment induced CLDN6 demethylation, inhibited MeCP2 binding to CLDN6 promoter and increased H3Ac and H4Ac in the promoter. In addition, TSA increased H4Ac, not H3Ac in the promoter. The chromatin structure of CLDN6 gene became looser than the control group after treating with 5-aza-dC in MCF-7 cells. 5-aza-dC up-regulated CLDN6 expression and suppressed migration and invasion in MCF-7 cells, whereas CLDN6 silence restored tumor malignance in MCF-7 cells. DNA methylation down-regulates CLDN6 expression through MeCP2 binding to the CLDN6 promoter, deacetylating H3 and H4, and altering chromatin structure, consequently promoting migratory and invasive phenotype in MCF-7 cells. | Authentic |
Text : Lung cancer remains the leading cause of cancer mortality because of its metastatic potential and high malignancy. The discovery of new applications for old drugs is a shortcut for cancer therapy. We recently investigated the antitumor effect of digoxin, a well-established drug for treating heart failure, against nonsmall cell lung cancer A549 and H1299 cells. Digoxin inhibited the proliferation and colony-forming ability of the two cell lines and arrested the cell cycle at the G0/G1 phase in A549 cells and the G2/M phase in H1299 cells. Mitochondria-mediated apoptosis was induced in A549 cells but not in H1299 cells after treatment with digoxin. Moreover, digoxin inhibited the migration, invasion, adhesion and epithelial-mesenchymal transition of A549 and H1299 cells. Autophagy was induced in both cell lines after treatment with digoxin, with an increase in autophagosome foci. In addition, digoxin inhibited the phosphorylation of Akt, mTOR and p70S6K, signaling molecules of the PI3K/Akt pathway that are known to be involved in tumor cell survival, proliferation, metastasis and autophagy. Our findings suggest that digoxin has the potential to be used for therapy for human nonsmall cell lung cancer, but further evidence is required. | Authentic |
Text : The dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of non-small cell lung cancer (NSCLC). However, the mechanisms by which miR-516a-5p contributes to NSCLC remain unclear. The association between miR-516a-5p expression and the clinicopathological characteristics and prognosis in patients with NSCLC was analyzed by The Cancer Genome Atlas (TCGA) data set. The targets of miR-516a-5p were identified by bioinformatic analysis and luciferase report assay. MTT and soft agar assays were conducted to investigate the function of miR-516a-5p in NSCLC cells. We found that the expression of miR-516a-5p was decreased in NSCLC tissues and associated with the age, pathological stage, and tumor size, acting as an independent prognostic factor of tumor recurrence in patients with NSCLC. Restoration of miR-516a-5p inhibited the cell viability and anchorage-independent growth of NSCLC cells, but its inhibitor had the opposite effects. Histone cluster 3 H2A (HIST3H2A) was further identified as a direct target of miR-516a-5p and displayed a negative correlation with miR-516a-5p expression in NSCLC tissues. Overexpression of HIST3H2A reversed the anti-proliferation effects induced by miR-516a-5p and acted as an independent prognostic factor of poor survival in patients with NSCLC. Altogether, our findings demonstrate that miR-516a-5p may function as a tumor suppressive factor in NSCLC cells by targeting HIST3H2A and might represent a potential indicator of tumor recurrence in patients with NSCLC. | Authentic |
Text : Pancreatic cancer (PC) is a devastating malignant disease with a poor prognosis. This study aimed to investigate the role of urothelial carcinoma associated 1 (UCA1) in the progression of PC. Our results revealed that long noncoding RNA (lncRNA) UCA1 was overexpressed in PC tissues compared with adjacent histologically normal tissues. A downregulated level of UCA1 was also detected in five human PC cell lines (SW1990, BxPC-3, MiaPaCa-2, PANC-1, and CAPAN-1) compared with normal pancreatic duct epithelial HPDE cells. The proliferation of PC cells was inhibited after UCA1 was suppressed by a lentiviral vector. The cell apoptosis rate was largely promoted by downregulating UCA1. Further research revealed that microRNA (miRNA)-135a is a direct target of UCA1. The expression of miR-135a was decreased in PC tissues and cell lines compared with control groups. In addition, the decreased level of miR-135a was elevated by adding miR-135a mimic in SW1990 cells transfected with lncRNA UCA1. Similarly, an upregulated level of miR-135a was downregulated by adding miR-135a inhibitor in SW1990 cells transfected with UCA1 siRNA. Luciferase activity assay further confirmed the targeting relationship between UCA1 and miR-135a. Moreover, miR-135a reversed the effect of UCA1 on cell apoptosis rate and cell viability in SW1990 cells. The migration and invasion capacities of PC cells were suppressed by UCA1. siRNA was then enhanced by the miR-135a inhibitor. In vivo, UCA1 siRNA effectively suppressed tumor growth and the expression of migration markers. Taken together, our research revealed that UCA1 works as an oncogene by targeting miR-135a. The UCA1-miR-135a pathway regulated the growth and metastasis of PC, providing new insight in the treatment of PC. | Counterfeit |
Text : A better understanding of the immune profile of non-small cell lung cancer (NSCLC) and the immunomodulatory impact of chemotherapy is essential to develop current therapeutic approaches. Herein, we collected peripheral blood from 20 healthy donors and 50 patients with advanced NSCLC, before and after chemotherapy, followed by phenotypic analysis of lymphocyte subsets and assessment of the correlation between their post-chemotherapy levels and progression-free survival (PFS). Results showed that, before chemotherapy, the levels of CD8+ lymphocytes, PD-1+CD4+, Th2, and Th17 cells were elevated in patients' peripheral blood, in contrast to natural killer (NK) cells and Th1 cells. Besides, there was no remarkable difference in the frequency of PD-1+CD8+ cells between patients and healthy controls. After chemotherapy, the levels of CD8+ lymphocytes, NK, Th2, Th17, and Treg were declined, in contrast to the level of Th1 cells which was markedly increased. Importantly, chemotherapy had no impact on the frequencies of PD-1+CD8+ and PD-1+CD4+ cells. PFS was significantly better in patients with low percentage of PD-1+CD4+ T cells than those with high percentage. Patients with high content of Th1 cells showed longer PFS than those with low content. The low percentages of Th17 and Treg cells were correlated with longer PFS, even though the difference did not reach statistical significance. In conclusion, the imbalance of lymphocyte subsets is a hallmark of NSCLC. Furthermore, the high level of PD-1+CD4+ cells plays a crucial role in the progression of NSCLC and could be used as a prognostic marker; and the high level of Th1 could predict better clinical outcomes of chemotherapy. | Authentic |
Text : Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability. | Authentic |
Text : Metastatic Prostate cancer (PCa) cells have gained survival and invasive advantages. Epidermal growth factor (EGF) receptor is a receptor tyrosine kinase, which may mediate signalling to promote progression and invasion of various cancers. In this study, we uncovered the molecular mechanisms underlying the interconnection among the androgen receptor (AR), matrix metalloproteinase-9 (MMP9) and EGFR in promoting PCa progression. Immunohistochemical analysis of the tissue microarrays consisting of primary and metastatic PCa tissues was performed. The clinical importance of EGFR and its association with survivals were analyzed using three cohorts from MSKCC Prostate Oncogenome Project dataset (For primary tumors, n = 181; for metastatic tumors n = 37) and The Cancer Genome Atlas Prostate Adenocarcinoma Provisional dataset (n = 495). Targeted overexpression or inhibition of the proteins of interests was introduced into PCa cell lines. Treatment of PCa cell lines with the compounds was conducted. Immunoblot analysis was performed. We showed that AR, MMP-9 and EGFR are interconnect factors, which may cooperatively promote PCa progression. Altered EGFR expression was associated with poor disease-free survival in PCa patients. Induced overexpression of AR led to an increase in the expression of EGFR, p-GSK-3β and decrease in p27 expression in PCa cell lines in the presence of androgen stimulation. Overexpression of MMP9 significantly induced EGFR expression in PCa cells. Inhibition of PIP5K1α, a lipid kinase that acts upstream of PI3K/AKT greatly reduced expressions of AR, MMP-9 and EGFR. Our findings also suggest that PCa cells may utilize AR, EGFR and MMP-9 pathways in androgen-dependent as well as in castration-resistant conditions. Our data suggest a new therapeutic potential to block cancer metastasis by targeting AR, EGFR and MMP-9 pathways in subsets of PCa patients. | Authentic |
Text : Breast cancer has a diverse aetiology characterized by the heterogeneous expression of hormone receptors and signalling molecules, resulting in varied sensitivity to chemotherapy. The adverse side effects of chemotherapy coupled with the development of drug resistance have prompted the exploration of natural products to combat cancer. Lactoferricin B (LfcinB) is a natural peptide derived from bovine lactoferrin that exhibits anticancer properties. LfcinB was evaluated in vitro for its inhibitory effects on cell lines representing different categories of breast cancer and in vivo for its suppressive effects on tumour xenografts in NOD-SCID mice. The different breast cancer cell lines exhibited varied levels of sensitivity to apoptosis induced by LfcinB in the order of SKBR3>MDA-MB-231>MDA-MB-468>MCF7, while the normal breast epithelial cells MCF-10A were not sensitive to LfcinB. The peptide also inhibited the invasion of the MDA-MB-231 and MDA-MB-468 cell lines. In the mouse xenograft model, intratumoural injections of LfcinB significantly reduced tumour growth rate and tumour size, as depicted by live imaging of the mice using in vivo imaging systems (IVIS). Harvested tumour volume and weight were significantly reduced by LfcinB treatment. LfcinB, therefore, is a promising and safe candidate that can be considered for the treatment of breast cancer. | Authentic |
Text : Acute lymphoblastic leukemia (ALL) is the most prevalent of pediatric cancers. Neuroepithelial cell-transforming 1 (NET1) has been associated with malignancy in a number of cancers, but the role of NET1 in ALL development is unclear. In the present study, we investigated the effect of NET1 gene in ALL cell proliferation and chemoresistance. We analyzed GEO microarray data comparing bone marrow expression profiles of pediatric B-cell ALL samples and those of age-matched controls. MTT and colony formation assays were performed to analyze cell proliferation. ELISA assays, Western blot analyses, and TUNEL staining were used to detect chemoresistance. We confirmed that NET1 was targeted by miR-206 using Western blot and luciferase reporter assays. We identified NET1 gene as one of the most significantly elevated genes in pediatric B-ALL. MTT and colony formation assays demonstrated that NET1 overexpression increases B-ALL cell proliferation in Nalm-6 cells. ELISA assays, Western blot analyses, and TUNEL staining showed that NET1 contributes to ALL cell doxorubicin resistance, whereas NET1 inhibition reduces resistance. Using the TargetScan database, we found that several microRNAs (miRNAs) were predicted to target NET1, including microRNA-206 (miR-206), which has been shown to regulate cancer development. To determine whether miR-206 targets NET1 in vitro, we transfected Nalm-6 cells with miR-206 or its inhibitor miR-206-in. Western blot assays showed that miR-206 inhibits NET1 expression and miR-206-in increases NET1 expression. Luciferase assays using wild-type or mutant 3'-untranslated region (3'-UTR) of NET1 confirmed these findings. We ultimately found that miR-206 inhibits B-ALL cell proliferation and chemoresistance induced by NET1. Taken together, our results provide the first evidence that NET1 enhances proliferation and chemoresistance in B-ALL cells and that miR-206 regulates these effects by targeting NET1. This study therefore not only contributes to a greater understanding of the molecular mechanisms underlying B-ALL progression but also opens the possibility for developing curative interventions. | Authentic |
Text : In this study, oxaliplatin (OX) liposomes surface-modified with glycyrrhetinic acid (GA) were developed by the film-dispersion method. Their morphology, physical and chemical properties, and in vitro release performance were investigated. The transmission electron microscope (TEM) image showed that most liposomes were spherical particles with similar size and uniform dispersion. Both OX-liposomes and GA-OX-liposomes had an average size of 90 nm. They were negatively charged, with zeta potentials of -20.6 and -21.3 mV, respectively, and the entrapment efficiency values of both were higher than 94%. In vitro data showed that the application of liposomes could prolong the OX release. The relatively high correlation coefficient values obtained from analyzing the amount of drug released versus the square root of time depicted that release followed the Weibull model. No significant changes were observed after the addition of GA to the liposomes. In vivo, the relatively long time to reach the maximum plasma concentration of OX-liposomes suggested a sustained-release profile of liposomes, which was consistent with the results of the in vitro release study. The increased area under the curve and maximum plasma concentration of OX-liposomes and GA-OX-liposomes demonstrated an increased absorption. The drug concentration in tissues indicated that the GA-modified liposomes delivered OX mainly to liver after intravenous administration. In addition, no severe signs, such as appearance of epithelial necrosis or sloughing of epithelial cells, were detected in histology studies. | Counterfeit |
Text : Cellular senescence acts as a barrier against tumorigenesis. The CD40L transgene, expressed in some tumor cells, not only becomes visible to antigen-presenting cells but also actively catalyzes its own termination. Here, we evaluated the effect of a membrane-bound mutant form of human CD40L (CD40L-M) on senescence and the senescence-associated secretory phenotype (SASP) in non-small cell lung cancer (NSCLC). CD40 expression levels in the NSCLC cell lines A549/TR, A549/DDP and H460 were examined by flow cytometry. Senescent cells and tissues were identified via SA-β-gal activity. Cell proliferation was visualized by EdU labeling. qRT-PCR, Western blotting, and immunofluorescence staining were conducted to assess mRNA and protein expression levels of CD40L, γ-H2A.X, p65, p-p65, IκBα, p53, p21 and p16. Cytokines secreted from transfected cells were tested by ELISA and cell migration assay. Capsid tyrosine-modified rAAV5-CD40L-M was packaged and carried out in vivo. Overexpression of CD40L-M promoted senescence, inhibited proliferation, increased DNA damage-associated γ-H2A.X, and initiated the SASP in CD40-positive NSCLC cells. NF-κB signaling was activated by CD40L-M overexpression in these cells. Knockdown of NF-κB partially overcame senescence and failed to induce SASP. Furthermore, increased p53 and p21 protein levels induced by CD40L-M were also reduced following NF-κB suppression. These data showed that the membrane-bound CD40L mutant may promote cellular senescence and initiate the SASP of NSCLC cells in an NF-κB-dependent manner. Therefore, CD40L-M-induced senescence may be a potential approach to protect against lung adenocarcinoma. | Authentic |
Text : This study aimed to investigate the function and mechanism of microRNA-143 (miR-143) in the occurrence and development of breast cancer (BC). A total of 30 BC tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast tissues were obtained to detect the levels of miR-143, extracellular signal-regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143 with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis. MCF-7 cells were transiently transfected with miR-143 mimic, miR-143 inhibitor, miR-143 mimic/inhibitor + si-ERK5, si-MAP3K7 or si-cyclin D1. Then, cell growth was evaluated by MTT assay and the expressions of phospho-ERK5 (p-ERK5), ERK5, p-MAP3K7, MAP3K7 and cyclin D1 were detected by western blotting. Results showed that, compared with noncancerous tissues or NC breast tissues, miR-143 level was decreased, while p-ERK5, ERK5, p-MAP3K7 and MAP3K7 expressions were increased in BC tissues (all P<0.01). The miR-143 level was negatively correlated with the mRNA level of ERK5 or MAP3K7 (r=-4.231 or r=-4.280, P<0.01). In addition, up-regulated miR-143 significantly decreased the expressions of p-ERK5, ERK5, p-MAP3K7, MAP3K7 and cyclin D1 (all P<0.01), as well as cell viability in MCF-7 cells (all P<0.05) while the effect of down-regulated miR-143 was the opposite. In conclusion, both ERK5 and MAP3K7 may be the target genes of miR-143. Increased expression of miR-143 can inhibit cell growth, which may be associated with ERK5 and MAP3K7 expressions in BC. | Authentic |
Text : The tripartite motif (TRIM) family comprises more than 70 members involved in the regulation of many cellular pathways. TRIM32 acts as an E3 ubiquitin ligase and has been reported to participate in many human cancers. Here, we aimed to investigate the role of TRIM32 in gastric cancer (GC) and the clinical implications. High expression of TRIM32 was observed in GC tissues and cell lines, and was significantly associated with poor prognosis. Knockdown TRIM32 expression remarkably suppressed the proliferation, migration, and invasion of GC cells in vitro and tumour growth in vivo, whereas overexpression of TRIM32 yielded the opposite results. Western blotting and quantitative reverse-transcription PCR (qRT-PCR) analyses revealed that up-regulation of TRIM32 significantly enhanced expression of β-catenin protein and of its downstream targets TCF1, cyclin D1, Axin2 and MMP7 mRNAs. Moreover, we found that the mechanism behind the TRIM32-promoted GC progression was related to the β-catenin signalling pathway. Collectively, these data suggest that TRIM32 promotes GC cell proliferation, migration, and invasion by activating the β-catenin signalling pathway. | Authentic |
Text : Hepatocellular carcinoma (HCC) is a biologically complex disease. Combination chemotherapy is a good strategy after surgery treatment. In this study, we report that berberine combined with HMQ1611 (BCH) had a good synergistic effect on the HCC. Our findings concluded that BCH showed good inhibition on the HCC proliferation and colony formation, which attributed to cell cycle arrest by BCH at G1 phase through impairing the expression of cyclinD1, cyclinE, and cdc2 and downregulated the phosphorylation of Akt, mTOR, and ERK. Moreover, BCH negatively regulated Wnt signaling pathway by upregulating the Axin and inhibiting the nuclear translocation of β-catenin. BCH suppressed the phosphorylation of LRP5/6, GSK3β, the expression of Wnt5a, Frizzled8, CK1, and APC, as well as the nucleus protein included MMP2, MMP3, MMP9, and c-myc. The above data of Wnt signaling regulators contributed to inhibition by BCH on cell migration. In vivo studies, BCH significantly suppressed the growth of SMMC-7721 xenograft tumors through downregulating Ki67 and β-catenin, as well as upregulating Axin and p-β-catenin. In conclusion, the results revealed that BCH exhibited potential antitumor activities against human liver cancer in vitro and in vivo, and the potential mechanism underlying these activities depended on the inhibition of the Wnt/β-catenin signaling pathway. | Authentic |
Text : Propofol has been widely used in lung cancer resections. Some studies have demonstrated that the effects of propofol might be mediated by microRNAs (miRNAs). This study aimed to investigate the effects and mechanisms of propofol on lung cancer cells by regulation of miR-1284. A549 cells were treated with different concentrations of propofol, while transfected with miR-1284 inhibitor, si-FOXM1, and their negative controls. Cell viability, migration, and invasion, and the expression of miR-1284, FOXM1, and epithelial-mesenchymal transition (EMT) factors were detected by CCK-8, Transwell, qRT-PCR, and Western blot assays, respectively. In addition, the regulatory and binding relationships among propofol, miR-1284, and FOXM1 were assessed, respectively. Results showed that propofol suppressed A549 cell viability, migration, and invasion, upregulated E-cadherin, and downregulated N-cadherin, vimentin, and Snail expressions. Moreover, propofol significantly promoted the expression of miR-1284. miR-1284 suppression abolished propofol-induced decreases of cell viability, migration, and invasion, and increased FOXM1 expression and the luciferase activity of FOXM1-wt. Further, miR-1284 negatively regulated FOXM1 expression. FOXM1 knockdown reduced cell viability, migration, and invasion by propofol treatment plus miR-1284 suppression. In conclusion, our study indicated that propofol could inhibit cell viability, migration, invasion, and the EMT process in lung cancer cells by regulation of miR-1284. | Counterfeit |
Text : Increasing evidence indicates that long noncoding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level and the function of SPRY4-IT1 in the progression of gastric cancer (GC) have been rarely reported. Here we found that SPRY4-IT1 was upregulated in GC. In vitro experiments revealed that SPRY4-IT1 knockdown significantly inhibited GC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell growth. Further functional assays indicated that SPRY4-IT1 overexpression significantly promoted cell migration and invasion. Bioinformatics analysis predicted that there is a SPRY4-IT1/miR-101-3p/AMPK axis in GC progression. A dual-luciferase reporter system validated the direct interaction of SPRY4-IT1, miR-101-3p, and AMPK. Western blot verified that the inhibition of SPRY4-IT1 decreased AMPK expression. Furthermore, silencing SPRY4-IT1 suppressed GC growth in vivo. Importantly, we demonstrated that SPRY4-IT1 was upregulated in serum exosomes from GC patients and correlated with cancer metastasis. Altogether, silencing SPRY4-IT1 suppresses the progression of GC by interacting with miR-101-3p and decreasing inhibiting AMPK expression. Taken together, our study demonstrates that SPRY4-IT1 could act as a potential therapeutic target for GC patients. | Authentic |
Text : Due to the high mortality and rapid disease progression, ovarian cancer remains one of the most common malignancies threatening the health of women. The present study was conducted to explore the anticancer effects and the underlying mechanisms of poricoic acid A (PAA), the main components of Poria cocos, on ovarian cancer. We investigated the anticancer effects of different concentrations of PAA in the SKOV3 cell line. Cell viability and proliferation were examined by CCK-8 assay. Cellular migration and invasion were assessed by the scratch and Transwell migration assays, respectively. The effect of PPA on cell apoptosis was measured by flow cytometry and caspase-3/8/9 colorimetric assay. Western blot was performed to detect protein level changes related to apoptosis and mTOR signaling pathways. The in vivo anticancer effect of PAA was evaluated using xenograft tumorigenesis model in nude mice. Our results showed that PAA suppressed SKOV3 cellular viability, migration, and invasion in a dosage-dependent manner. Flow cytometry results demonstrated PAA treatment could induce SKOV3 cell apoptosis. In addition, increased ratio of LC3-II/LC3-I (a marker for autophagosome formation) was observed after PAA treatment, as well as inhibition of m-TOR and p70s6k phosphorylation. In nude mice, PAA treatment reduced the xenograft tumor weight by 70% (P<0.05). In conclusion, our data suggested that PAA induced apoptosis and autophagy in ovarian cancer via modulating the mTOR/p70s6k signaling axis. | Authentic |
Text : Emerging evidence suggests long non-coding RNA (lncRNA) could sponge microRNAs (miRs) and monitor gene expression. In this study, we intended to search the network involving lncRNA MINCR/miR-223/ZEB1 in nasopharyngeal carcinoma (NPC) cell radiosensitivity. MINCR expression in NPC tissues, precancerous lesions and chronic nasopharyngeal mucosal inflammation tissues, and in NP460, CNE2 and CNE2R cells was detected. The associations between MINCR expression and prognosis and radiotherapy efficacy of NPC patients were evaluated. The interactions among MINCR, miR-223 and ZEB1 were verified via dual luciferase reporter gene assay, RNA pull-down and FISH assays. The gain- and loss-of-functions were performed to explore their effects on NPC cell viability, apoptosis and radiosensitivity. Levels of MINCR, miR-223, ZEB1, and AKT/PI3K-related proteins were detected after different treatments. An in vivo analysis was carried out in nude mice. Consequently, MINCR was upregulated in NPC, and linked with worse prognosis and radiotherapy efficacy. MINCR intervention weakened NPC cell radioresistance. MINCR sponged miR-223 to regulate ZEB1. Inactivating AKT eliminated the increased radioresistance of CNE2 cells induced by overexpressing MINCR. Briefly, MINCR diminished NPC cell radiosensitivity by sponging miR-223, increasing ZEB1 and activating the AKT/PI3K axis. This study may offer novel insight for NPC treatment. | Authentic |
Text : Bladder cancer (BC) is the most common of those affecting the urinary tract, and a significant proportion of the cases are attributable to tobacco use as well as occupational and environmental factors. The aim of this study is to estimate the current incidence of BC in an industrialized area in northeastern Spain and to analyze its time trends over three decades from an ecological perspective. Patients diagnosed with histologically confirmed primary BC, during 2018-2019, in an area in northeastern Spain (430,883 inhabitants) were included. Crude and age-standardized incidence rates were estimated per 100,000 person-years based on the number of individuals getting their first diagnosis. An exploratory time trend analysis was carried out to describe the evolution in tobacco use and occupational or environmental risk factors and the incidence of BC in the same area from the 1990s. 295 patients were included (age 72.5 ± 10.3 years; 89.8% men). The crude rate was 62.6 (95% CI: 51.9-73.2) for men and 6.8 (95% CI: 3.4-10.3) for women. The annual rate adjusted to the European Standard Population was 85.3 (95% CI:75.0-95.5) for men and 7.0 (95% CI:4.5-9.5) for women. From 1994 to 2018, the prevalence of smokers decreased in men (42.3% to 30.9%) as well as in the active population working in the industry (44.36% to 22.59%). Nevertheless, the car fleet, especially diesel, has increased considerably. The annual mean concentrations of air (PM10, PM2.5, O3, and NO2) and water (nitrates, arsenic, trihalomethanes) pollutants were within the regulatory limit values, but not the maximum levels. The incidence of BC is one of the highest in men but not in women, despite the decrease in tobacco use and industrial activity (perhaps related to high latency after carcinogen exposure cessation) and despite the control of environmental pollution (the maximum regulatory limit probably needs to be lowered). Finally, a similar exposure to the carcinogen would result in a gender-specific differential incidence. | Authentic |
Text : To explore the expression of extracellular vesicle-derived lncZEB1-AS1 in esophageal cancer and its role in esophageal cancer progression. The extracellular vesicles (EVs) from esophageal cancer patients (n = 26) and normal subjects (n = 26) were isolated by differential centrifugation. The expression of lncZEB1-AS1 in EVs was detected by Real-time PCR (polymerase chain reaction). The clinical data of normal subjects and patients were analyzed. In addition, the concentration of EVs and lncZEB1-AS1 in blood samples from normal subjects and esophageal cancer patients were assessed. After co-culture of esophageal cancer cell line EC109 and EVs with or without lncZEB1-AS1 knockdown, cell proliferation was detected by CCK-8 assay. The possible target microRNAs of lncZEB1-AS1 in cytoplasm were predicted with miRcode, followed by correlation analysis of lncZEB1-AS1 and miR-214. Through literature review, lncZEB1-AS1 positively regulates ZEB1 expression, which was consistent with our result. Quantitative Real-time PCR showed that the serum levels of EVs and the content of lncZEB1-AS1 in EVs from esophageal cancer patients were significantly higher than those in normal controls. LncZEB1-AS1 was overexpressed in esophageal cancer cells co-cultured with EVs of esophageal cancer patients. CCK-8 results indicated that EC109 cells co-cultured with EVs of esophageal cancer patients had stronger proliferative capacity. miRcode showed that miR-214 ranked the first of microRNAs that lncZEB1-AS1 might target, and miR-214 expression was significantly increased after lncZEB1-AS1 knockdown in EC109. After overexpressing lncZEB1-AS1 in EC109 or co-culturing EVs of esophageal cancer patients with EC109 cells, we found that lncZEB1-AS1 positively regulates ZEB1. In contrast, interfering with the expression of lncZEB1-AS1 in esophageal cancer cell lines can effectively reduce the expression of ZEB1. EVs in the peripheral blood from esophageal cancer patients promote esophageal cancer progression by delivering lncZEB1-AS1 to esophageal cancer cells and targeting miR-214. | Authentic |
Text : Increasing evidence has supported the prognostic and therapeutic values of long non-coding RNAs (LncRNAs) in human tumorigenesis. Hepatocellular carcinoma (HCC), as one of the most refractory diseases, continues to warrant investigation for novel clues to enable early diagnosis. In the present study, the role of LncRNA AB019562 in cell proliferation and metastasis was investigated in HCC. Reverse transcription‑quantitative polymerase chain reaction analysis was performed to determine the expression of AB019562 in clinical HCC samples and cultured HCC cells. In addition, a specific small interfering RNA against AB019562 was designed and transfected into HCC cells. A3‑(4,5‑ dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and a transwell assay were used to assess the effects of AB019562 knockdown on cell proliferation and metastasis, respectively. The results revealed that the expression of AB019562 was increased 4‑fold in the clinical HCC tissues, compared with adjacent non‑cancerous tissue counterparts. AB019562 was differentially expressed in the HCC cell lines. The knockdown of AB019562 reduced the rate of cell proliferation by 28.6% in HepG2 cells and by 24% in SMMC‑7721 cells. Cell cycle assays revealed that the proportion of cells in the G0/G1 phase was significantly increased, whereas those in the S and G2/M phases were decreased in the AB019562‑knockdowncells. The results of the transwell assay showed that the knockdown of AB019562 inhibited cell migration abilities by up to 67% in the HepG2 cells and 63% in the SMMC‑7721 cells, and significantly suppressed invasive abilities by up to 75% in the HepG2 cells and 60% in the SMMC‑7721 cells. Furthermore, AB019562 knockdown increased the apoptotic rates of the two cell lines and activated the expression of caspase‑3, but not caspase‑8. These data demonstrated the pro‑oncogenic properties of AB019562 and suggested that AB019562 may serve as a novel biomarker for the diagnosis and treatment of patients with HCC. | Authentic |
Text : Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1. QRT-PCR was used to examine the mRNA levels of the IGFBP1 gene. Small interfering RNAs (siRNAs) were used to knockdown PPARγ and IGFBP1 genes. Exogenously expression of IGFBP1 and Sp1 was determined by transient transfection assays. IGFBP1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. In vivo nude mice xenograft model and bioluminescent imaging system were used to confirm the findings. We showed that emodin induced cell cycle arrest of NSCLC cells. Emodin increased PPARγ protein and luciferase reporter activity, which were abolished by inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK and AMPK. Silencing of PPARγ abrogated emodin-inhibited cell growth and cell cycle arrest. Furthermore, emodin elevated IGFBP1 mRNA, protein, and promoter activity through activation of PPARγ. Intriguingly, overexpressed Sp1 attenuated emodin-induced IGFBP1 expression, which was not observed in cells with silenced PPARγ gene. Moreover, silencing of IGFBP1 gene blunted emodin-induced inhibition of cell growth and cell cycle arrest. On the contrary, overexpressed IGFBP1 enhanced emodin-induced phosphorylation of AMPKα and ERK1/2, and restored emodin-inhibited growth in cells with silenced endogenous IGFBP1 gene. Emodin also inhibited growth of lung xenograft tumors and Sp1, and increased IGFBP1 and PPARγ protein expressions In vivo. Collectively, our results show that emodin inhibits growth of non-small-cell lung cancer (NSCLC) cells through ERK and AMPKα-mediated induction of PPARγ, followed by reduction of Sp1. This in turn induces IGFBP1 gene expression. Thus, the signaling cascades, positive feedback loop and cooperative interplay between transcription factors-induced the expression of IGFBP1 gene contribute to the overall responses of emodin. This study provides a novel mechanism by which emodin inhibits growth of human lung cancer cells. | Authentic |
Text : Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in the DNA damage response. SNP rs1136410 C>T, the most studied polymorphism in PARP-1 gene, is highly implicated in the susceptibility of cancer. However, the roles of PARP-1 rs1136410 C>T on cancer risk vary from different studies. We comprehensively screened all qualified publications from several databases, including PubMed, EMBASE, MEDLINE, CNKI and Wanfang. The searching was updated to April 2020. Our meta-analysis included 60 articles with 65 studies, comprised of a total of 23 996 cases with cancer and 33 015 controls. Overall, pooled data showed that the PARP-1 rs1136410 C>T polymorphism was significantly but a border-line associated with an increased risk of overall cancer (CC vs. TT/TC: OR = 1.11, 95% CI = 1.00-1.24; C vs T: OR = 1.07, 95% CI = 1.01-1.14). Subgroup analysis indicated that rs1136410 C allele contributed to high risk among gastric, thyroid, and cervical cancer, but lower risk among brain cancer. Furthermore, increased cancer risk was detected in the subgroups of Asian, controls from population-based design studies, and HWE ≤ 0.05 studies. Sensitivity analysis and Egger's test showed that results of the meta-analysis were fairly stable. The current study indicated that PARP1 rs1136410 C>T polymorphism may have an impact on certain types of cancer susceptibility. | Authentic |
Text : Colorectal cancer (CRC) has become the fourth leading cause of cancer-related death in the worldwide. It is urgent to find more effective therapeutic strategies for it. Reactive oxygen species (ROS) play multiple roles in normal cellular physiology processes. Thus, a certain level of ROS is essential to keep normal cellular function. However, the accumulation of ROS shows dual roles for cells, which is mainly dependent on the concentration of ROS, the origin of the cancer cell and the activated signaling pathways during tumor progression. In general, moderate level of ROS leads to cell damage, DNA mutation and inflammation, which promotes the initiation and development of cancer. Excessive high level of ROS induces cancer cell death, showing an anti-cancer role. ROS are commonly higher in CRC cells than their normal counterpart cells. Therefore, it is possible that ROS induce cell death in cancer cells while not affecting the normal cells, demonstrating lower side effects. Besides, ROS also play a role in tumor microenvironment and drug resistance. These multiple roles of ROS make them a promising therapeutic target for cancer. To explore potential ROS-target therapies against CRC, it is worth to comprehensively understanding the role of ROS in CRC and therapy. In this review, we mainly discuss the strategies of ROS in CRC therapy, including direct CRC cell target and indirect tumor environment target. In addition, the influences of ROS in drug resistance will also been discussed. | Authentic |
Text : The aim of this study was to investigate the clinical value of liquid biopsy as a primary source for variant analysis in lung cancer. In addition, we sought to characterize liquid biopsy variants and to correlate mutational load to clinical data. Circulating cell-free DNA was extracted from plasma from patients with lung cancer (n = 60) and controls with benign lung disease (n = 16). Variant analysis was performed using the AVENIO ctDNA Surveillance kit and the results were correlated to clinical and variant analysis data from tumor tissue or cytology retrieved from clinical routine diagnostics. There were significantly more variants detected in lung cancer cases compared to controls (p = 0.011), but no difference between the histological subgroups of lung cancer was found (p = 0.465). Furthermore, significantly more variants were detected in patients with stage IIIb-IV disease compared to patients with stage I-IIIa (median 7 vs 4, p = 0.017). Plasma cfDNA mutational load was significantly associated with overall survival (p = 0.010). The association persisted when adjusted for stage and ECOG performance status (HR: 3.64, 95% CI 1.37-9.67, p = 0.009). Agreement between tumor and plasma samples significantly differed with stage; patients with stage IIIb-IV disease showed agreement in 88.2% of the cases with clinically relevant variants, compared to zero cases in stage I-IIIa (p = 0.004). Furthermore, one variant in EGFR, two in KRAS, and one in BRAF were detected in plasma but not in tumor samples. This study concludes that in the vast majority of advanced NSCLC patients a reliable variant analysis can be performed using liquid biopsy from plasma. Furthermore, we found that the number of variants in plasma is associated with prognosis, possibly indicating a strategy for closer follow up on this crucial patient group. | Authentic |
Text : The latest 2021 WHO classification redefines glioblastoma (GBM) as the hierarchical reporting standard by eliminating glioblastoma, IDH-mutant and only retaining the tumor entity of "glioblastoma, IDH-wild type." Knowing that subclassification of tumors based on molecular features is supposed to facilitate the therapeutic choice and increase the response rate in cancer patients, it is necessary to carry out molecular classification of the newly defined GBM. Although differentiation trajectory inference based on single-cell sequencing (scRNA-seq) data holds great promise for identifying cell heterogeneity, it has not been used in the study of GBM molecular classification. Single-cell transcriptome sequencing data from 10 GBM samples were used to identify molecular classification based on differentiation trajectories. The expressions of identified features were validated by public bulk RNA-sequencing data. Clinical feasibility of the classification system was examined in tissue samples by immunohistochemical (IHC) staining and immunofluorescence, and their clinical significance was investigated in public cohorts and clinical samples with complete clinical follow-up information. By analyzing scRNA-seq data of 10 GBM samples, four differentiation trajectories from the glioblastoma stem cell-like (GSCL) cluster were identified, based on which malignant cells were classified into five characteristic subclusters. Each cluster exhibited different potential drug sensitivities, pathways, functions, and transcriptional modules. The classification model was further examined in TCGA and CGGA datasets. According to the different abundance of five characteristic cell clusters, the patients were classified into five groups which we named Ac-G, Class-G, Neo-G, Opc-G, and Undiff-G groups. It was found that the Undiff-G group exhibited the worst overall survival (OS) in both TCGA and CGGA cohorts. In addition, the classification model was verified by IHC staining in 137 GBM samples to further clarify the difference in OS between the five groups. Furthermore, the novel biomarkers of glioblastoma stem cells (GSCs) were also described. In summary, we identified five classifications of GBM and found that they exhibited distinct drug sensitivities and different prognoses, suggesting that the new grouping system may be able to provide important prognostic information and have certain guiding significance for the treatment of GBM, and identified the GSCL cluster in GBM tissues and described its characteristic program, which may help develop new potential therapeutic targets for GSCs in GBM. | Authentic |
Text : To elucidate whether microRNA-142 could regulate the development of nasopharyngeal carcinoma (NPC) by mediating gene of phosphate and tension homology deleted on chromosome ten (PTEN) expression. The microRNA-142 expression in NPC tissues and paracancerous tissues was detected by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between the microRNA-142 expression and the prognosis of NPC patients was analyzed. MicroRNA-142 expression in NPC cell lines was determined as well. By transfection of microRNA-142 inhibitor or negative control, biological performances of NPC cells were accessed through cell counting kit-8 (CCK-8), colony formation, wound healing, and transwell assay. Dual-luciferase reporter gene assay was conducted to verify the binding condition between microRNA-142 and its target gene PTEN. Rescue experiments were carried out by co-transfection of microRNA-142 inhibitor and si-PTEN, followed by detecting the invasive capacity of NPC cells. Protein expressions of relative genes in the PI3K/AKT pathway after the microRNA-142 knockdown in NPC cells were determined by Western blot. MicroRNA-142 was highly expressed in NPC tissues than that of paracancerous tissues, which was correlated with poor prognosis of NPC patients. MicroRNA-142 was also highly expressed in NPC cells. Downregulated microRNA-142 inhibited proliferative, migratory, and invasive capacities of NPC cells. Dual-luciferase reporter gene assay verified that microRNA-142 could directly bind to PTEN. Knockdown of PTEN could reverse the inhibitory effect of microRNA-142 on invasive capacity of NPC cells. Finally, Western blot results demonstrated that the microRNA-142 knockdown inhibited the PI3K/AKT pathway in NPC cells. MicroRNA-142 is highly expressed in NPC. MicroRNA-142 enhances the proliferative and invasive capacities of NPC cells by inhibiting PTEN expression, thus promoting NPC development. | Authentic |
Text : Ovarian cancer is the malignant tumor of the female reproductive system with the highest fatality rate. Tolerance to chemotherapeutic drugs such as paclitaxel (PTX) occurring in the very early stage is one of the important factors of the poor prognosis of ovarian cancer. Herein, we aim to study the dysregulation of a particular circular RNA (circRNA), circCELSR1 (hsa_circ_0063809), and its role in the progression and PTX resistance of ovarian cancer. The high expression of circCELSR1 in PTX-resistant tissues of ovarian cancer and PTX-resistant ovarian cancer cells (SKOV3/PTX and HeyA-8/PTX) was determined by microarray analyses and quantitative real-time PCR. Cell Counting Kit-8 (CCK-8) assays were performed to investigate the effect of circCELSR1 on PTX sensitivity of ovarian cancer cells. Flow cytometer assays were used to detect cell cycle and apoptosis of ovarian cancer cells. The effect of circCELSR1 on ovarian cancer cells was assessed in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays. By microarray (5 PTX-resistant ovarian cancer tissues νs 5 PTX-sensitive ovarian cancer tissues) and qRT-PCR (36 normal ovarian tissues and ovarian cancer tissues) we identified circCELSR1 to be dramatically highly expressed in ovarian cancer samples and correlated with PTX resistance. Compared with sensitive cell lines, circCELSR1 was also highly expressed in PTX-resistant ovarian cancer cell lines, and circCELSR1 silencing enhanced PTX-induced cytotoxicity in ovarian cancer cells. Meanwhile, the inhibition of circCELSR1 also caused ovarian cancer cell G0/G1 arrest and an increase in apoptosis. In vivo studies revealed that circCELSR1 was stably inhibited in a xenograft mouse model and inhibited the growth of ovarian cancer. Furthermore, we demonstrated that circCELSR1 acts as a sponge for miR-1252 and verified that forkhead box 2 (FOXR2) is a novel target of miR-1252. In this study, we explored the specific mechanisms of PTX resistance and tumor progress of ovarian cancer due to circCELSR1; presented the circCELSR1-miR-1252-FOXR2 axis and its role in ovarian cancer drug sensitivity and progression; and suggest that the results may provide an experimental basis for clinical application. | Authentic |
Text : Abnormal lipid metabolism is closely related to the malignant biological behavior of tumor cells. Such abnormal lipid metabolism provides energy for rapid proliferation, and certain genes related to lipid metabolism encode important components of tumor signaling pathways. In this study, we analyzed pancreatic cancer datasets from The Cancer Genome Atlas and searched for prognostic genes related to lipid metabolism in the Molecular Signature Database. A risk score model was built and verified using the GSE57495 dataset and International Cancer Genome Consortium dataset. Four molecular subtypes and 4249 differentially expressed genes (DEGs) were identified. The DEGs obtained by Weighted Gene Coexpression Network Construction analysis were intersected with 4249 DEGs to obtain a total of 1340 DEGs. The final prognosis model included CA8, CEP55, GNB3 and SGSM2, and these had a significant effect on overall survival. The area under the curve at 1, 3 and 5 years was 0.72, 0.79 and 0.87, respectively. These same results were obtained using the validation cohort. Survival analysis data showed that the model could stratify the prognosis of patients with different clinical characteristics, and the model has clinical independence. Functional analysis indicated that the model is associated with multiple cancer-related pathways. Compared with published models, our model has a higher C-index and greater risk value. In summary, this four-gene signature is an independent risk factor for pancreatic cancer survival and may be an effective prognostic indicator. | Authentic |
Text : Cholangiocarcinoma (CCA), a lethal malignancy of the biliary epithelium, is the second most common primary liver cancer. The poor prognosis of CCA is due to the high rate of tumour invasion and distant metastasis. We found that the RNA-binding protein LIN28B, a known regulator of microRNA biogenesis, stem cell maintenance, and oncogenesis, is expressed in a subpopulation of CCA patients. To further investigate the potential role of LIN28B in CCA pathogenesis, we studied the effect of LIN28B overexpression in the cholangiocyte cell line MMNK-1 and cholangiocarcinoma cell lines HuCCT-1 and KKU-214. Here, we show that enhanced LIN28B expression promoted cancer stem cell-like properties in CCA, including enhanced cell migration, epithelial-to-mesenchymal transition (EMT), increased cell proliferation and spheroid formation. Proteomic analysis revealed TGF-β-induced protein (TGFBI) as a novel LIN28B target gene, and further analysis showed upregulation of other components of the TGF-β signalling pathway, including TGF-β receptor type I (TGFBRI) expression and cytokine TGFB-I, II and III secretion. Importantly, the small molecule TGF-β inhibitor SB431542 negated the effects of LIN28B on both cell migration and clonogenic potential. Overexpression of TGFBI alone promoted cholangiocarcinoma cell migration and EMT changes, but not spheroid formation, suggesting that TGFBI partially contributes to LIN28B-mediated aggressive cell behaviour. These observations are consistent with a model in which TGF-β and LIN28B work together to form a positive feedback loop during cholangiocarcinoma metastasis and provide a therapeutic intervention opportunity. | Authentic |
Text : Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets. | Authentic |
Text : Recent theoretical and experimental studies indicate that long-chain noncoding RNAs (lncRNAs) are essential for the growth and differentiation of cells and the occurrence and development of tumors in epigenetics, but the regulation of lncRNA on gene expression, transcriptional activation, and transcriptional interference in diseases is still unclear. There is an urgent need for effective methods to discover significant lncRNAs with their functions on gene regulatory mechanisms. For this purpose, a new method of extracting significant lncRNA based on pathway crosstalk and dysfunction caused by the differentially expressed genes in lung adenocarcinoma (LUAD) was proposed. The pathway analysis method based on global influence (PAGI) was first applied to find the feature genes that play an important role in the crosstalks of disease-related pathways. Then to explore the hub lncRNAs, the weighted gene coexpression network analysis (WGCNA) was used to construct coexpression models of the feature genes and lncRNAs. The experiment results showed that 64 out of the 322 hub lncRNAs were closely related to the clinical features of patients with LUAD. Among them, nine lncRNAs (UCA1, LINC00857, PVT1, PCAT6, LINC00460, LINC00319, AP000553.1, AP000439.2, and AP005233.2) were identified to be tightly correlated with non-small-cell lung cancer (NSCLC) pathways. In summary, we offer an effective way to extract significant lncRNA by dysfunctional pathway crosstalk in LUAD which allows the selected lncRNAs with more biologically interpreted and reproducible results. This method can be applied to other diseases and provide useful information for understanding the pathogenesis of human cancer. | Authentic |
Text : Endosialin, alternatively named tumor endothelial marker 1 (TEM1) or CD248, is a bulk transmembrane glycoprotein expressed both in developing and adult tissues undergoing active physiological or pathological angiogenesis. Endosialin is often overexpressed in tumors, particularly in stromal cells and in vessels-covering pericytes, and its transcription is induced by hypoxia via HIF-2 transcription factor. Based on the expression pattern, molecular characteristics and phenotypes of genetic models, endosialin has been proposed to function as a receptor implicated in sprouting angiogenesis, vasculogenesis and/or pruning of vessels. Here we provide an overview of the recent knowledge linking endosialin to diverse aspects of angiogenesis. Based on data-mining, our experimental data and available literature, we suggest that endosialin cross-talks with both pro- and anti-angiogenic signals and ECM components, and participates in dynamic vascular remodeling, which facilitates tumor growth. Tumor-selective targeting of endosialin may therefore contribute to improvement of existing anti-angiogenic therapies. | Authentic |
Text : Introduction: Coronary artery disease originates from the blockage of the inner walls of the coronary arteries due to a plaque buildup. Accumulating studies have highlighted the role of microRNAs (miRs) delivered by exosomes in the progression of coronary artery disease. Thus, the current study was to elucidate the role and mechanism by which miR-25-3p influences oxidized low density lipoprotein (ox-LDL)-induced coronary vascular endothelial cell (CVEC) inflammation. Methods: Primarily isolated CVECs were treated with ox-LDL to induce inflammation. Atherosclerosis models were induced in ApoE-/- mice and the peripheral blood platelet exosomes (PLT-Exo) were extracted and induced by thrombin, followed by co-culture with CVECs. The relationship between miR-25-3p and A disintegrin and metalloprotease 10 (Adam10) as well as the involvement of the NF-κB signaling pathway was evaluated. In order to evaluate the effect of PLT-Exo containing miR-25-3p on ox-LDL-induced CVEC inflammation, lipid accumulation and fibrosis, miR-25-3p mimic/inhibitor (in vitro), miR-25-3p agomir (in vivo), and si-Adam10 were delivered. Results: MiR-25-3p was expressed poorly in ox-LDL-induced CVECs and vascular tissues but exhibited high levels of expression in thrombin-induced PLT-Exo of atherosclerosis models of ApoE-/- mice. CVECs endocytosed PLT-Exo upregulated the miR-25-3p expression. Adam10 was identified as a target gene of miR-25-3p. The thrombin-induced activated PLT-Exo carrying miR-25-3p reduced Adam10 expression to inhibit ox-LDL-induced CVEC inflammation and lipid deposition through downregulating levels of α-smooth muscle actin, Collagen I a1, Collagen III a1, triglycerides, total cholesterol, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, the NF-κB signaling pathway participated in the inhibitory effect of PLT-Exo carrying miR-25-3p. Conclusion: Collectively, PLT-Exo overexpressing miR-25-3p attenuates ox-LDL-induced CVEC inflammation in ApoE-/- mouse models of atherosclerosis. | Counterfeit |
Text : Osteosarcoma (OS) is still a disease with high mortality from malignant tumors in children and adolescents. Due to its poor treatment, this study explored the involvement of lncRNA ZFAS1/microRNA-135a (miR-135a)/apurinic/apyrimidinic exonuclease 1 (APEX1) axis in the regulation of OS growth and metastasis. ZFAS1, miR-135a and APEX1 expression in OS tissues and cells were tested by RT-qPCR and western blot analysis. MG63 cells were transfected with sh-ZFAS1, miR-135a mimic or their controls to unearth theirs functions in the proliferation, colony formation, migration, invasion, cycle entry and apoptosis of MG63 cells by MTT and EdU, colony formation assays, flow cytometry, and Transwell assay, severally. The proliferation related factor (Ki-67, CyclinD1), apoptosis related factor (Bax, Bcl-2) and migration related factor (MMP2, MMP9) protein levels were tested. Tumor volume and weight were detected by subcutaneous tumor xenograft in nude mice. Overexpressed ZFAS1 and APEX1, and down-regulated miR-135a existed in OS tissues and cells. Silenced ZFAS1 or elevated miR-135a inhibited colony formation and proliferation, cycle progression, migration and invasion while promoted apoptosis of MG63 cells. Silenced ZFAS1 or elevated miR-135a suppressed tumor volume and weight of OS in vivo. LncRNA ZFAS1 promoted APEX1 expression by competitively binding with miR-135a. This study indicates that silenced ZFAS1 or up-regulated miR-135a restrained migration, proliferation and invasion and promoted apoptosis of OS MG63 cells. This study provides a possible theoretical basis for studying the regulatory mechanism of ZFAS1/miR-135a/APEX1 signaling axis on the growth and metastasis of OS. | Counterfeit |
Text : Photodynamic therapy (PDT) is an emerging effective strategy for cancer treatment. Compared with conventional cancer therapies, such as surgery, chemotherapy, and radiotherapy, PDT has shown great promise as a next-generation cancer therapeutic strategy owing to its many advantages such as non-invasiveness, negligible observed drug resistance, localized treatment, and fewer side effects. One of the key elements in photodynamic therapy is the photosensitizer (PS) which converts photons into active cytotoxic species, namely, reactive oxygen species (ROS). An ideal PS for photodynamic therapy requires the efficient generation of ROS, high stability against photo bleaching, and robust performance in different environments and concentrations. PSs with aggregation-induced emission (AIE) characteristics have drawn significant attention, in that they can overcome the aggregation- caused quenching effect that is commonly seen in the case of fluorescence dyes and provide excellent performance at high concentrations or in their condensed state. Moreover, organic nanomaterials with AIE characteristics, or AIE dots, have played an increasingly significant role in assisting PDT based on its excellent ROS generation efficiency and simultaneous imaging feature. This review summarizes the recent advances on the molecular design of AIE PSs and AIE dots-based probes, as well as their emerging applications for enhanced anticancer PDT theranostics. | Authentic |
Text : Lung cancer is reported to be a major public health issue worldwide and the overall prognosis of patients remains poor. The expression levels of Livin and Survivin, of the inhibitors of apoptosis (IAP) family, are associated with prognostic significance in the majority of solid tumors. Therefore, in the presents study, short hairpin (sh)RNA expression vectors inhibiting the Livin and Survivin genes were constructed to examine the effects of the transfection of Livin shRNA and/or Survivin shRNA on the biological functions of tumor cells. The transfection efficiency was measured using fluorescence reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The cell growth inhibition ratio was measured using a CCK assay. Cell apoptosis following transfection and in tumor tissues were measured using a TUNEL assay, and a cancer xenograft model was used to investigate the effect of Livin shRNA and/or Survivin shRNA on tumor growth. The results indicated that the mRNA and protein expression levels were suppressed following the transfection of Livin and Survivin shRNA into tumor cells (P<0.05, compared with control group). The growth of tumor cells in vivo and in vitro was significantly inhibited following transfection with Livin and Survivin shRNA, compared with that in the other groups (P<0.05). Taken together, the transfection of cells with Livin and Survivin inhibited tumor growth in vivo and in vitro, with the co‑transfection of Livin and Survivin shRNA showing increased efficiency, compared with transfection of either the Livin vector or Survivin vector alone. The combined inhibition of Livin and Survivin may be a promising multitargeted gene therapeutic strategy in cancer treatment. | Authentic |
Text : Regulator of cullins-1 (ROC1) is a pivotal component of cullin-RING E3 ubiquitin ligases, which help to regulate distinct cellular processes by governing the degradation of various substrates. Because the role of ROC1 in gastric cancer is largely uncharacterized, we investigated the relationship between ROC1 expression and the prognosis of gastric cancer patients and explored the biological function of ROC1 and its underlying mechanisms in gastric cancer. Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the correlation between the carcinogenesis of gastric cancer and ROC1. SA-β-gal staining and the senescence-associated secretory phenotype (SASP) were used to assess ROC1 silencing-induced cellular senescence. A xenograft zebrafish model was used to evaluate the effects of BCL-XL and ROC1 co-silencing on tumor formation in vivo. High ROC1 expression was correlated with poor prognosis and a low 5-year survival rate of gastric cancer patients. ROC1 depletion significantly inhibited the growth of gastric cancer cells by sequentially inducing p21-mediated cellular senescence and mitochondrial-dependent apoptosis. Functional studies revealed successive upregulation of c-Jun, BCL-XL, and p21 upon ROC1 knockdown. BCL-XL suppression via RNA interference or a BH3 mimetic (ABT-737 or ABT-263) efficiently enhanced the anti-tumor effects of ROC1 knockdown. Equally as important, BCL-XL silencing strengthened ROC1 knockdown-induced apoptosis by blocking p21-mediated senescence. The c-Jun/BCL-XL/p21 axis promotes senescence to resist ROC1 knockdown-induced apoptosis in gastric cancer cells. Targeted inactivation of BCL-XL could sensitize gastric cancer cells to ROC1 knockdown in clinical practice. | Authentic |
Text : Long non‑coding RNAs (lncRNAs) have been identified as key regulatory factors in various biological processes. Their dysregulation has been observed in several types of human cancer, including gastric cancer (GC). The aim of the present study was to investigate the putative roles of the lncRNA DQ786243 in the progression of GC, as well as evaluate its diagnostic and therapeutic potential in GC. The expression of DQ786243 in 82 pairs of GC tissues and adjacent healthy tissues, as well as in three GC cell lines and a human normal gastric epithelial cell line, was assessed using reverse transcription‑quantitative polymerase chain reaction. In addition, the putative correlation between the expression of DQ786243 and various clinicopathological features of GC was investigated. Furthermore, the effects of silencing DQ786243 in GC cells were examined using RNA interference. Colony formation and Cell Counting kit‑8 assays were used to evaluate the effects of DQ786243 on GC cell proliferation, and Transwell and wound healing assays were used to examine GC cell migration and invasion. The results of the present study demonstrated that the expression of DQ786243 was significantly upregulated in GC tissues and cell lines compared with healthy control tissues and cells. Correlation analysis revealed a significant association between the expression of DQ786243 and the TNM stage, tumor size, depth of invasion and presence of lymph node metastasis in patients with GC. Furthermore, silencing the DQ786243 was demonstrated to inhibit proliferation, and impair the migration and invasion of GC cells. The present results suggested that DQ786243 may function as an oncogenic regulator via promoting the proliferation and metastasis of GC cells. Therefore, DQ786243 may have potential as a novel biomarker for the diagnosis of GC, and may also be a promising candidate for the development of novel therapeutic approaches for the treatment of patients with GC. | Authentic |
Text : Primary intraosseous squamous cell carcinoma (PIOSCC) derived from a odontogenic cyst is a rare form of odontogenic carcinoma. The incidence of carcinomas arising from odontogenic cysts is particularly uncommon and is reported to occur in 1-2 individuals for every 1,000 cases. The present case describes a 25-year-old man who was initially diagnosed with a chronically infected odontogenic cyst of the mandible. Biopsy and subsequent histology revealed the presence of squamous cell carcinoma. Therefore, neck dissection and hemimandibulectomy were performed. Ultimately, the situation in the mouth healed, though with a severe amount of scarring. Although the development of PIOSCC from an odontogenic cyst is rare, it should be included in the differential diagnosis for jaw bone radiolucency. | Authentic |
Text : This study investigates whether the circulating miR-155, let-7c, miR-21, and PTEN levels to be used in the differential diagnosis of patients with idiopathic granulomatous mastitis (IGM) and breast cancer (BC). Forty-five patients with BC, 50 patients with IGM, and 48 healthy volunteers were included in the study. Serum miR-21 expression was significantly higher in BC (fold change = 2.42) and IGM group (fold change = 1.33) compared to control (p < .001). Serum miR-155 and let-7c expression levels were significantly lower in both groups compared to the control group (p < .001). miR-21 expression in BC was significantly higher than IGM (fold change = 1.976; p < .001). PTEN levels in BC were significantly higher than IGM (p < .001) and significantly lower than the control group (p < .001); the IGM group was significantly lower than the control group (p < .001). In addition to radiological data, serum miR-21 and PTEN levels may be noninvasive biomarkers that can help differentiate IGM from BC. The results of the study will lead to future studies in the differential diagnosis of IGM and BC. | Authentic |
Text : Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres (< 3 kilobases, CSTs), but not average telomere length by itself, accounts for limited tissue renewal and turnover capacity. The impact of this parameter (which can be modified with different therapies) in chemotherapy-derived toxicity has not been studied.Blood from 115 treatment-naive patients from a clinical trial in early HER2-negative breast cancer that received weekly paclitaxel (80 mg/m2 for 12 weeks) either alone or in combination with nintedanib and from 85 healthy controls was prospectively obtained and individual CSTs and average telomere lenght were determined by HT Q-FISH (high-throughput quantitative FISH). Toxicity was graded according to NCI common toxicity criteria for adverse events (NCI CTCAE V.4.0). The variable under study was "number of toxic episodes" during the 12 weeks of therapy.The percentage of CSTs ranged from 6.5%-49.4% and was directly associated with the number of toxic events (R2 = 0.333; P < 0.001). According to a linear regression model, each 18% increase in the percentage of CSTs was associated to one additional toxic episode during the paclitaxel cycles; this effect was independent of the age or treatment arm. Patients in the upper quartile (> 21.9% CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019) episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average telomere length was unrelated to the incidence of side effects.The percentage of CSTs, but not the average telomere size, is associated with weekly paclitaxel-derived toxicity. | Authentic |
Text : Colon cancer is the most common digestive system malignancy, along with high mortality rate, familial transmissibility and hepatic metastasis. Our study investigated the role of long non-coding RNA H19 in colon cancer. We found that H19 was overexpressed in colon cancer tissues and cell lines, the interference of H19 by short hairpin RNA (shRNA) effectively decreased the migration and invasion of colon cancer cells (HT-29 and RKO). Besides, miR-138 was predicted a target of H19, and low expression of miR-138 was found in colon cancer tissues and cells. The silence of H19 strongly increased the expression of miR-138. The decreased level of miR-138 was elevated adding miR-138 mimic in RKO cells transfected with lncRNA-H19. Similarly, the upregulated level of miR-138 was downregulated adding miR-138 inhibitor in RKO cells transfected with H19 shRNA. The luciferase reporter confirmed the targeting reaction between H19 and miR-138. Moreover, the high-mobility group A (HMGA1) protein was predicted as a target of miR-138. HMGA1 was suppressed by H19 shRNA and could be up-regulated by miR-138 inhibitor. The migration and invasion ability of colon cancer was restrained by H19 shRNA and promoted by miR-138 inhibitor. Finally, the in vivo experiment revealed that H19 shRNA strongly reduced the tumor growth and tumor volume. H19 shRNA also inhibited metastasis via suppressing hepatic metastases and the expression of metastasis-related proteins. Taken together, our research indicated an H19-miR138-HMGA1 pathway in regulating the migration and invasion of colon cancer, providing new insight for treatment of colon cancer. | Counterfeit |
Text : Hepatocellular carcinoma (HCC), a type of primary liver cancer, is the second leading cause of cancer mortality worldwide. Increasing evidence suggests that dysfunction of microRNAs (miRNAs) plays an important role in human cancers. MicroRNA-888 (miR-888) has been reported to be upregulated in multiple cancers that have a high rate of metastasis. The purpose of this study was to explore the molecular mechanisms of miR-888 in HCC cell migration and invasion. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were employed to measure the levels of miR-888 and SMAD4 in HCC tissues and cell lines. To analyse the tissues and cell lines' migratory and invasive abilities, Transwell assays were performed. To confirm that miR-888 regulates SMAD4 expression in HCC, a dual-luciferase reporter assay was applied. MiR-888 was upregulated, while SMAD4 was downregulated, in HCC tissues and cell lines, and miR-888 and SMAD4 mRNA levels had a negative correlation. MiR-888 promoted cell migration and invasion in vitro. SMAD4 was thus confirmed as a direct and functional target of miR-888, and it could partially reverse the function of miR-888. MiR-888 promoted cell migratory and invasive abilities and suppressed the expression of SMAD4 in HCC. The newly identified miR-888/SMAD4 axis provides novel insight into the progression of HCC and offers a promising target for HCC therapy. | Authentic |
Text : Cancer patients face multiple challenges, such as infertility caused by exposure to gonadotoxic agents and gonadal irradiation during cancer treatment. Little is known about the health practitioners' knowledge and practice regarding fertility preservation and its available options in Saudi Arabia. Thus, this study is designed to evaluate the level of knowledge, attitude, and practice (KAP) towards fertility preservation in cancer patients among health practitioners in an environmental region in Saudi Arabia. The cross-sectional study was carried out between September 2020 and January 2021. A self-administered questionnaire was distributed among health practitioners from a variety of specialties who work closely with cancer patients. Out of 100 participants, 90% need more knowledge about fertility preservation. The lack of fertility preservation clinics in the patient's area and its unaffordable expenses significantly influenced the health practitioners' attitude towards fertility preservation discussion with cancer patients. The results revealed that 92% of the participants agreed that the Saudi Ministry of Health should establish practice guidelines and provide fertility preservation services for cancer patients. The present study showed that clinical practitioners' knowledge remains insufficient. Education of health practitioners and the establishment of practice guidelines and fertility preservation clinics for cancer patients are required. | Authentic |
Text : This study was intended to establish the predictive target of Shikonin (SK) against ovarian cancer using network pharmacology and to clarify the potential mechanism of SK in promoting apoptosis in ovarian cancer. Cell Counting Kit-8 assay, plate clone assays, LDH assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, and western blotting were used to assess the effect of SK on apoptosis of ovarian cancer cell lines (SKOV3 and A2780). Pharmacodynamic targets were used to predict the targets of SK and ovarian cancer. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses were used to analyze the biological functions and signal pathways of these targets. SK promoted apoptosis in ovarian epithelioid adenocarcinoma cells. SK-ovarian cancer pharmacodynamic target analysis screened 17 related genes. GO and KEGG analyses showed that SK affected the estrogen signaling pathway. SK inhibited the expression of GPER in SKOV3 and A2780 cells and downregulated the expression of EGFR, p-EGFR, PI3K, and p-AKT in a concentration-dependent manner. The apoptosis-promoting effect of SK was enhanced by GPER-specific agonist G1 and inhibited by the specific inhibitor G15. The expression of EGFR, p-EGFR, PI3K, and p-AKT was decreased by G1 and reversed by G15. SK also inhibited tumor growth in the SKOV3 xenograft model, and it acted synergistically with G1. However, the effect can be attenuated by G15 in vivo. In summary, SK may affect the apoptosis of ovarian cancer cells through GPER/EGFR/PI3K/AKT, and GPER may be a key target of SK in ovarian cancer cell apoptosis. | Authentic |
Text : To investigate the role of CAB39 in nasopharyngeal carcinoma (NPC) development and examine its expression level in NPC tumor samples. Immunohistochemistry staining of NPC tissue microarray was conducted to detect the expression of CAB39 protein in NPC tissues, and the clinical significance of CAB39 was evaluated. Lentivirus-mediated over-expression of CAB39 was designed to increase CAB39 expression in CNE-1 cells. Cell colony formation, cell cycle and CCK-8 proliferation experiments were performed to compare the proliferation ability of CNE-1 cells with or without CAB39 over-expression. Western blotting was conducted to examine downstream targets of CAB39. CAB39 expression was higher in tumor samples compared to normal tissue and the higher CAB39 expression was positively correlated to higher TNM stage and distant metastasis rate and non-keratinized state. Further, CAB39 over-expression dramatically increased the proliferation and colony formation of CNE-1 cells. Finally, higher p-JNK protein level was found in CAB39 over-expressing cells. CAB39 promotes the proliferation of CNE-1 cells via up-regulating p-JNK. | Authentic |
Text : The aim of this study is to elucidate whether and how miR-107 participates in the modulation of paclitaxel sensitivity in non small cell lung cancer (NSCLC). By qRT-PCR, we found that miR-107 is significantly down-regulated in paclitaxel-resistant A549/Taxol cells compared with corresponding paclitaxel-sensitive counterparts. Overexpression of miR-107 suppresses paclitaxel resistance of A549/Taxol cells through directly inhibiting Bcl-w. Overexpression of miR-107 promotes apoptosis and inhibits proliferation and mobility of A549/Taxol cells under treatment with paclitaxel in vitro. Moreover, miR-107 inhibits in vivo paclitaxel resistance in xenograft model. MiR-107/Bcl-w axis regulates paclitaxel chemoresistance through PI3K-Akt pathway. Our results suggest that up-regulation of miR-107 resensitizes paclitaxel-resistant NSCLC cells by targeting Bcl-w, which reveals a potential mechanism of miR-107 in reversing drug resistance. | Authentic |
Text : Malignant melanoma is a highly lethal disease, and advanced stages of melanoma have proven to be resistant to many chemotherapeutic drugs including temozolomide and paclitaxel. Cancer stem cells (CSCs) have been identified and isolated in different cancers including melanoma, and have been proven playing important role in the drug resistance. Retinoic acid (RA) is a promising anticancer agent, which can induce differentiation of CSCs. The main purpose of the present study was to evaluate the possible RA-induced differentiation of melanoma CSCs and sensitization of melanoma CSCs to paclitaxel. Our results show that CSCs of human melanoma A375 cells was more tolerant to paclitaxel than other non-CSCs melanoma cells. On the contrary, RA had stronger inhibitory effect on melanoma CSCs than on non-CSCs. At the same time, RA could arrest the cell cycle of CSCs and reduce the expression of Sox-2, Oct-4 in CSCs of melanoma, thereby induced the differentiation of CSCs and increased its sensitivity to paclitaxel. With this study we concluded that RA increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma, and the combined application of RA and paclitaxel may be more effective in the treatment of melanoma. | Authentic |
Text : Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early-stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circRNA-miRNA (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA-miRNA interaction which could be involved in breast cancer development. | Authentic |
Text : This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer. | Authentic |
Text : In order to study the application of nanoparticles in the diagnosis and treatment of pancreatic cancer, we retrospectively analyzed pancreatic cancer patients after operation. 60 cases of pancreatic cancer and surgical treatment were selected from our hospital. The time ranged from March 2018 to March 2019. The age ranged from 27 to 81 years. There were 36 males and 24 females, with an average age of 46.23 (7.63) years. Among them, the observation group consisted of nanotube artificial tubes, 16 males and 14 females, while the control group adopted nylon tube, male 18 and female 12. The patient was diagnosed by abdominal CT, and the patient's demographic data and basic clinical data were recorded at the same time. In this study, 60 patients were divided into groups and compared. The patients underwent surgical resection of pancreaticoduodenum and reconstruction of pancreaticoduodenal papillary duct. Among them, the observation group used nanocomposite artificial tube, while the observation group used nanocomposite artificial tube and placed drainage tube to drain the peritoneal effusion to prevent the effusion from forming in abdominal hypertension and infection. The amount of postoperative bleeding, operation time, and postoperative concomitant symptoms were observed, and the differences between the two materials were analyzed. The reconstruction of pancreaticoduodenal papillary duct with nanomaterials has certain advantages for postoperative recovery, reduces postoperative complications, reduces the probability of infection, and improves the therapeutic effect. | Authentic |
Text : MicroRNAs-491-5p (miR-491-5p) has been found to involve in tumor initiation and development in several tumors. However, the biological function and underlying molecular mechanism of miR-491-5p in non-small lung cancer (NSCLC) remain unclear. This study was therefore to investigate biological role of and underlying molecular mechanisms of in NSCLC. It was found that miR-491-5p expression was significantly downregulated in NSCLC tissues when compared with corresponding adjacent normal tissues (P<0.01), and the value was negatively related to advanced and tumor-node-metastasis (TNM) stage and lymph node metastasis (both P<0.01). We also demonstrate that restoration of miR-491-5p suppressed NSCLC cell proliferation by arresting NSCLC cells in the G1/G0 phase and accelerating apoptosis. miR-491-5p also inhibited cell migration and invasion in NSCLC cells. Mechanically, IGF2BP1 was identified as direct targets of miR-491-5p. And IGF2BP1 expression was significantly upregulated, and correlated negative with miR-491-5p expression in NSCLC tissues. In vivo assay showed thatmiR-491-5p suppressed tumor growth in nude model by repressing IGF2BP1 expression. Collectively, miR-491-5p functioned as a tumor suppressor in NSCLC by targeting IGF2BP1. Restoration of miR-491-5p expression may represent a promising therapeutic approach for targeting malignant NSCLC. | Counterfeit |
Text : Chronic renal failure (CRF) is a prolonged kidney condition characterized by decreased kidney function that can eventually develop into total kidney failure. The renin-angiotensin system (RAS) helps to regulate the balance between human bodily fluids and electrolytes. The aim of the present study was to investigate the effects of a prostacyclin analogue (beraprost sodium [BPS]) on the expression of key factors associated with local RAS activities in the renal tissues of rats with CRF. After a CRF rat model was successfully established, the levels of BUN, SCr, phosphorus, and calcium were detected by an automatic biochemistry analyzer. Furthermore, the activities of malondialdehyde (MDA) and superoxide dismutase (SOD) in rat renal tissues were measured using a colorimetric method, while the activity of angiotensin-converting enzyme (ACE) was determined by ultraviolet (UV) spectrophotometry. In situ hybridization was employed to determine the expression of angiotensin II type 1 receptor (AT). Finally, the positive expression rates of cells expressing important apoptotic proteins (Bax and Bcl-2) were determined, and the protein and mRNA levels of phosphatidylinositol 3-kinase (AKT) and key factors involved in the RAS (AT1, AT2, angiotensin ACE and angiotensinogen [AGT]) were evaluated by RT-qPCR and western blot analysis. Initial observations revealed that treatment with BPS decreased the levels of BUN, SCr and phosphorus but increased calcium levels in the renal tissues of CRF rats. Additionally, BPS reduced the levels of MDA while increasing the levels of SOD, ACE activity, and AT1 expression in the renal tissues of CRF rats. BPS inhibited glomerular hypertension and hyperfiltration; increased the mRNA and protein levels of AKT and AT2; and decreased the mRNA and protein levels of AT1, AGT, and ACE in the renal tissues of CRF rats. The results of this study demonstrate that BPS, a PGI2 analogue, inhibits the expression of key factors involved in the local RAS, resulting in a delay in the occurrence and development of CRF. The key findings of the present study ultimately highlight the potential of this PGI2 analogue as a promising therapeutic strategy for treating CRF. | Counterfeit |
Text : Discovery of the progression-associated genes and pathways in lung adenocarcinoma (LAD) has important implications in understanding the molecular mechanism of tumor development. However, few studies had been performed to focus on the changes of pathways in lung adenocarcinoma development using microarray expression profile. We performed a meta-analysis of 4 LAD microarray datasets encompassing 353 patients to reveal differentially expressed genes (DEGs) between normal lung tissues and LAD of different stages. Overall, 1 838 genes were found to be dys-regulated, and the adipogenesis, circadian rhythm, and Id pathways were significantly changed. Interestingly, most of the genes from the same gene family (such as Interleukin receptor, Matrix metallopeptidase, Histone cluster and Minichromosome maintenance complex component families) were found to be up-regulated (or down-regulated). Real-time PCR (qRT-PCR) was applied to validate the expression of randomly selected 18 DEGs in LAD cell lines. In the pathway analysis among stages, Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways, which were involved in cancer cell proliferation and metastasis, were showed to be significantly regulated in stages other than IA. Genes involved in adipogenesis and Id pathways might play important roles in development of LADs. The similar trend of expression of the gene family members suggested coordinate regulation in tumor progression. Three pathways (Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways) significantly regulated in stages other than stage IA suggested that genes and pathways conferring invasive character might be activated in the preinvasive stage IB, while the Oxidative stress and the Glycolysis/Gluconeogenesis pathways might have strong connections to cisplatin-based chemotherapy. The insignificantly regulated three pathways in stage IA might be used in early-stage detection of LAD. | Authentic |
Text : The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC). Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group. TACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC. | Authentic |
Text : Long noncoding RNA (lncRNA) H19 is emerging as a vital regulatory molecule in the progression of different types of cancer and miR-675 is reported to be embedded in H19's first exon. However, their function and specific mechanisms of action have not been fully elucidated. The aim of this study was to identify a novel lncRNA-microRNA-mRNA functional network in gastric cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the relative expression of H19 and miR-675 in normal (GES-1) and gastric cancer cell lines (SGC-7901, SGC-7901/DDP) as well as in tumor tissues. Gain and loss of function approaches were carried out to investigate the potential roles of H19/miR-675 in cell proliferation and apoptosis. Moreover, Fas associated via death domain (FADD) was validated to be the target of miR-675 via luciferase reporter assay. Western blotting was used to evaluate the protein expression of related signaling pathway. In our study H19 and miR-675 were increased in gastric cancer cell lines and tissues. Overexpression of H19 and miR-675 promoted cell proliferation and inhibited cell apoptosis, whereas knockdown of H19 and miR-675 inhibited these effects. By further examining the underlying mechanism, we showed that H19/miR-675 axis inhibited expression of FADD. FADD downregulation subsequently inhibited the caspase cleavage cascades including caspase 8 and caspase 3. Taken together, our results point to a novel regulatory pathway H19/miR-675/ FADD/caspase 8/caspase 3 in gastric cancer which may be potential target for cancer therapy. | Authentic |
Text : Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial-mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a Cancer Stem Cell (CSC) model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis. The miRNAs are related to epigenetic event and additionally affect epigenetic pathways. Recent evidence demonstrates that epigenetic mechanisms such as DNA methylation may control miRNA expression. Because each miRNA may regulate several target genes, dysregulation of miRNA caused by aberrant DNA methylation patterns of the locus may influence important downstream pathways. Furthermore, some miRNAs is believed to regulate important DNA methylator factors. Any disruption or modification of this intricate network can contribute to the disease process; thus, it is essential to understand these changes. Advancements in new sequencing technologies to detect DNA methylation patterns has provided the opportunity to determine differentially methylated regions (DMRs) of the miRNA locus and their effect on expression profiles to improve BC diagnosis and treatment. The current review examines the interplay of DNA methylation mechanisms and miRNA function in invasive tumorigenesis, specifically EMT and CSC of BC, to highlight its potential for advancements on BC etiology, diagnosis, and therapy. | Authentic |
Text : Epidemiological studies and animal models suggest a link between high levels of dietary fat intake and an increased risk of developing breast cancer. Hyperinsulinemia is a feature of obesity, diabetes, and metabolic syndrome that is associated with an increased breast cancer risk. Insulin is a hormone involved in metabolic regulation of carbohydrate. However, it is also a growth factor that mediates proliferation and migration. Linoleic acid (LA) is a fatty acid that induces migration and invasion in breast cancer cells. In the present study, we demonstrate, for the first time, that treatment with LA increases IR and IGF1R expression through a Free Fatty Acid Receptor 4 (FFAR4)-, lipooxygenases (LOXs)-, and SRC-dependent pathway in MDA-MB-231 breast cancer cells, and similarly induces an increase of IR expression in MCF-7 breast cancer cells. In addition, insulin induces tyrosine phosphorylation of IR/IGF1R and migration in MDA-MB-231 cells pretreated with LA, whereas it augments the increase in migration in MCF-7 cells pretreated with LA. Pretreatment of MDA-MB-231 cells with LA induces invasion, proliferation, and increase the MMP-9 secretion induced by insulin. In summary, our findings demonstrate that treatment with LA induces a higher response to insulin in breast cancer cells. | Authentic |
Text : Translationally controlled tumor protein (TCTP) represents an exquisite target for cancer differentiation therapy, because it was most strikingly down-regulated in tumor reversion experiments. Since TCTP is identical with the histamine releasing factor, antihistamic drugs may inhibit TCTP. Indeed, antihistaminics, such as promethazine, thioridazine, perphemazine and chlorpromazine reveal antiproliferative effects. The aim of this investigation was to study antihistaminic drugs as new TCTP inhibitors to inhibit tumor growth. Levomepromazine and buclizine showed higher in silico binding affinities to TCTP among 12 different antihistaminic compounds including the control drugs, promethazine and hydroxyzine by using Autodock4 and AutodockTools-1.5.7.rc1. Recombinant human TCTP was codon-optimized, expressed in E. coli and purified by chitin affinity chromatography. For experimental validation of in silico data, we applied microscale thermophoresis. Levomepromazine bound with a Kd of 57.2 μM (p < 0.01) and buclizine with a Kd of 433μM (p < 0.01) to recombinant TCTP. Both drugs inhibited MCF-7 breast cancer cell growth in resazurin assays. TCTP expression was down-regulated after treatment with the two drugs. Cell cycle was arrested in the G1 phase without apoptosis as confirmed by the expression of cell cycle and apoptosis-regulating proteins. Annexin V-PI staining and Trypan blue exclusion assay supported that the two drugs are cytostatic rather than cytotoxic. Induction of differentiation with two drugs was detected by the increased appearance of lipid droplets. In conclusion, levomepromazine and buclizine inhibited cancer cell growth by binding to TCTP and induction of cell differentiation. These compounds may serve as lead compounds for cancer differentiation therapy. | Authentic |
Text : A new class of pharmacologically active mixed-ligand complexes (1a-2a) [MII(L)2 (bpy)], where L = 2-(4-morpholinobenzylideneamino)phenol), bpy = 2,2'-bipyridine, MII = Cu (1a), and Zn (2a), were assigned an octahedral geometry by analytical and spectral measurements. Gel electrophoresis showed that complex (1a) demonstrated the complete DNA cleavage mediated by H2O2. The overall DNA-binding constants observed from UV-vis, fluorometric, hydrodynamic, and electrochemical titrations were in the following sequence: (1a) > (2a) > (HL), which suggests that the complexes might intercalate DNA, a possibility that is further supported by the biothermodynamic characteristics. The binding constant results of BSA by electronic absorption and fluorometric titration demonstrate that complex (1a) exhibits the highest binding effectiveness among others, which means that all compounds could interact with BSA through a static approach, additionally supported by FRET measurements. Density FunctionalTheory (DFT) and molecular docking calculations were relied on to unveil the electronic structure, reactivity, and interacting capability of all substances with DNA, BSA, and SARS-CoV-2 main protease (Mpro). These observed binding energies fell within the following ranges: -7.7 to -8.6, -7.2 to -10.2, and -6.7 to -8.2 kcal/mol, respectively. The higher reactivity of the complexes compared to free ligand is supported by the Frontier MolecularOrbital (FMO) theory. The in vitro antibacterial, cytotoxic, and radical scavenging characteristics revealed that complex (1a) has the best biological efficacy compared to others. This is encouraged because all experimental findings are closely correlated with the theoretical measurements. | Authentic |
Text : High-risk human papillomavirus (HR-HPV) infections are among the most important factors for cervical carcinogenesis. However, whether patients infected with HR-HPV eventually develop a malignant tumor, largely depends on epithelial-mesenchymal transition (EMT), which plays an extraordinary role in the process of carcinogenesis and metastasis. Therefore, we evaluated the protein levels of EMT-related genes in normal cervical squamous epithelium, cervical intraepithelial neoplasia (CIN), and cervical squamous cell carcinoma (SCC) by tissue microarray and immunohistochemical staining. By comparing the expression of EMT-related proteins in 31 cases of cervical tumors and tumor adjacent tissues and exploring the relationship between HPV16 oncogenes and EMT in vitro, we found that Twist2 protein levels were significantly higher in CIN and cervical cancer than in normal cervical squamous epithelial samples (p<0.01 and p<0.001, respectively). This finding corresponded with the decreased expression of E-cadherin in cervical cancer. The difference in the expression of Twist2 and E-cadherin between 31 cases of cervical tumors and tumor adjacent tissues was statistically significant (p<0.01). HPV16 oncogenes were able to induce morphological alterations in the SiHa cell line, upregulate the expression of Twist2 and vimentin, downregulate E-cadherin in vitro, and exert an effect on invasion. Thus, joint detection of Twist2 and E-cadherin expression can help evaluate and provide greater insight into cervical carcinogenesis and progression. | Authentic |
Text : Liver cancer metastasis is known to be a poor prognosis and a leading cause of mortality. To overcome low therapeutic efficacy, understanding the physiological properties of liver cancer metastasis is required. However, the metastatic lesion is heterogeneous and complex. We investigate the distribution of lipids using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in an experimental metastasis model. We obtained the differentially expressed mass peaks in comparison between normal sites and metastatic lesions. The relationship of mass to charge ratio (m/z) and intensity were measured, m/z-indicated species were analyzed by MALDI-MS/MS analysis, and identification of these mass species was confirmed using the METASPACEannotation platform and Lipid Maps®. MALDI-MSI at m/z 725.6, 734.6, 735.6, 741.6, 742.6, 744.6, 756.6, and 772.6 showed significantly higher intensity, consistent with the metastatic lesions in hematoxylin-stained tissues. Sphingomyelin SM [d18:0/16:1], phosphatidylcholine (PC) [32:0], PC [31:0], PC [31:1], and PE [36:2] were highly expressed in metastatic lesions. Our results could provide information for understanding metastatic lesions. It suggests that the found lipids could be a biomarker for the diagnosis of metastatic lesions. | Authentic |
Text : This study aims to explore the role of long noncoding RNA (lncRNA)-HOX transcript antisense intergenic RNA (HOTAIR) in the occurrence and progression of glioma. Fresh glioma and normal brain tissues were classified into a glioma group (n = 67) and a normal group (n = 64) respectively. U87 cells were assigned into the blank, sh-NC, and sh-HOTAIR groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine HOTAIR expression. Cell proliferation, cell cycle and cell apoptosis rates were detected by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Scratch test and transwell assay were conducted for cell migration and invasion. Orthotopic glioma tumor model in nude mice was established by inoculating tumor cell suspension. Hematoxylin-Eosin (HE) staining was used to observe the growth and invasion of orthotopic glioma tumors. The expression of HOTAIR and cell viability was found to be lowest in the sh-HOTAIR group among the three groups. The sh-HOTAIR group exhibited a higher apoptotic rate and lower number of cell migration compared with the blank and sh-NC groups. Additionally, the speed of wound healing was slower, the migration distance decreased and the survival time of nude mice was extended in the sh-HOTAIR compared to the other groups. Moreover, the sh-HOTAIR group demonstrated reduced lesion sizes and inflammation, no convulsions or hemiplegia and lesser number of satellite metastases. Our findings support that down-regulation of HOTAIR could inhibit cell proliferation, promote cell apoptosis as well as suppress cell invasion and migration in the progression of glioma. | Counterfeit |
Text : The aim of this study was to explore the regulatory role of TRIM66 in the development of hepatocellular carcinoma (HCC), and to investigate its underlying mechanism. A total of 88 pairs of HCC tissues and para-cancerous tissues were surgically resected. The expression of TRIM66 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between TRIM66 expression and clinic-pathologic characteristics of HCC patients was analyzed. Follow-up data of enrolled HCC patients were collected for survival analysis. Subsequently, TRIM66 expression in HCC cells was determined by qRT-PCR as well. By constructing si-TRIM66, the biological performances of transfected HCC cells were determined using cell counting kit-8 (CCK-8), colony formation and transwell assay. Western blot was performed to measure the protein expressions of relative genes in epithelial-mesenchymal transition (EMT) pathway. Finally, HCC cells were co-transfected with si-TRIM66 and pcDNA-E-cadherin, followed by detection of invasive and migratory abilities. TRIM66 was highly expressed in HCC tissues compared with that of para-cancerous tissues. High expression of TRIM66 was positively correlated with tumor stage, lymph node metastasis and distant metastasis, whereas not correlated with age and sex of HCC patients. Kaplan-Meier curves revealed that a higher expression of TRIM66 was associated with worse prognosis of HCC. Similarly, TRIM66 was also highly expressed in HCC cells. The knockdown of TRIM66 in HCC cells significantly inhibited the proliferative, invasive and migratory abilities of transfected cells. However, TRIM66 down-regulation significantly induced cell apoptosis. Western blot results showed that TRIM66 knockdown in HCC cells markedly downregulated the protein expressions of E-cadherin, N-cadherin, Vimentin and β-catenin. The inhibited migration and invasion of HCC cells resulted from TRIM66 knockdown were partially reversed by E-cadherin overexpression. TRIM66 is highly expressed in HCC, which is positively correlated with tumor stage, lymph node metastasis and distant metastasis of HCC patients. In addition, TRIM66 promotes the malignant progression of HCC by inhibiting E-cadherin through the EMT pathway. | Authentic |