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Text : In this research, we explored the effect of long non-coding RNA (lncRNA) AOC4P on gastrointestinal stromal tumor (GIST) cells. The expression of lncRNA AOC4P in tissues was detected by real-time PCR (RT-PCR). The epithelial-mesenchymal transition (EMT)-related proteins in tissues were analyzed by Western blot. The experiment included negative control group (CN), silence AOC4P group (si AOC4P), and silence negative control group (si CT). RT-PCR, MTT, Scratch, Transwell, and Annexin V-FITC methods were used to detect the expression of lncRNA AOC4P, cell proliferation, cell migration ability, cell invasion ability, and apoptosis, respectively. The EMT-related proteins including TGF-β, ZEB1, Vimentin, Snail, and E-cadherin were analyzed by Western blot. The expression of lncRNA AOC4P and the expression of EMT-related proteins in high-risk GISTs were higher than that in low- and intermediate-risk GISTs (P<0.05). It was revealed that cell proliferative migration and invasive ability in si AOC4P group was decreased than that in CN and si CT groups (P<0.05), and cell apoptosis in si AOC4P group was higher than that in si CT group. The results of Western blot demonstrated that the expression of TGF-β1, ZEB1, Vimentin, and Snail in si AOC4P group were lower than that in si CT and CN group (P<0.05), and the expression of E-cadherin in si AOC4P group was higher than that in si CT and CN group (P<0.05). | Authentic |
Text : In the present study, we explored the anti-tumor and anti-angiogenesis effects of chrysophanol, and to investigate the underlying mechanism of the chrysophanol on anti-tumor and anti-angiogenesis in human lung cancer. The viability of cells was measured by CCK-8 assay, cell apoptosis was measured by Annexin-FITC/PI staining assay, and the cell migration and invasion were analyzed by wound-healing assay and transwell assay. ROS generation and mitochondrial membrane potential were analyzed by DCFH-DA probe and mitochondrial staining kit. Angiogenesis was analyzed by tube formation assay. The expression of CD31 was analyzed by immunofluorescence. The levels of proteins were measured by western blot assay. The anti-tumor effects of chrysophanol in vivo were detected by established xenograft mice model. In this study, we found that the cell proliferation, migration, invasion, tube formation, the mitochondrial membrane potential, and the expression of CD31 were inhibited by chrysophanol in a dose-dependent manner, but cell apoptotic ratios and ROS levels were increased by chrysophanol in a dose-dependent manner. Furthermore, the effects of chrysophanol on A549, H738, and HUVEC cell apoptotic rates were reversed by the ROS inhibitor NAC. Besides, the effects of chrysophanol on HUVEC cell tube formation were reversed by the HIF-1α inhibitor KC7F2 and the VEGF inhibitor axitinib in vitro. Moreover, tumor growth was reduced by chrysophanol, and the expression of CD31, CD34, and angiogenin was suppressed by chrysophanol in vivo. Our finding demonstrated that chrysophanol is a highly effective and low-toxic drug for inhibition of tumor growth especially in high vascularized lung cancer. | Counterfeit |
Text : Metastatic retroperitoneal tumors constitute an end-stage disease with poor prognosis that represents a heavy global health burden. The present study aimed to explore the efficacy of irreversible electroporation ablation (IRE) therapy in patients with end-stage retroperitoneal tumors. Between April 2016 and September 2017, three patients with unresectable retroperitoneal malignant tumors were enrolled. Among these cases, ultrasound (US)-guided IRE was palliatively performed for targeting 3 tumors (1 tumor per patient) located around the abdominal aorta. Post-treatment contrast-enhanced US (CEUS) and contrast-enhanced computed tomography (CECT) scans were subsequently performed to evaluate the area adjacent to the ablation zone and determine the prognosis. During the follow-up, the cases experienced a reduction of pain (mean score of 5.8 decreased to 2.2, based on the visual analogue scale), and had an overall survival rate ranging from 2 to 11 months. Case 1 remained alive at the time of submission of this study, but case 2 died within 2 months and case 3 within 11 months due to liver metastases of the primary tumor. At the 3-week follow-up, the CEUS image for case 1 exhibited a contrast defect with a sufficient ablation margin, in accordance with the CECT at 1.5 months following IRE, exhibiting complete tumor necrosis without contrast enhancement. Overall, these results suggest that US-guided percutaneous IRE may be effective in the treatment of end-stage retroperitoneal tumors. However, further studies are required to substantiate the conclusions of the present study. The present clinical trial was registered at clinicaltrials.gov (ID: NCT02822066) on June 20th, 2016. | Authentic |
Text : Drug resistance is a serious challenge in cancer chemotherapy. Alterations in the intracellular concentration and homeostasis of calcium (Ca2+) may contribute to the development of drug resistance. To investigate the mechanism of drug resistance in leukemia, the present study rendered human chronic myelogenous leukemia K562 cells resistant to the cytotoxic effect of doxorubicin by progressively adapting the sensitive parental K562 cells to doxorubicin. The resulting cells were termed K562/DOX. Subsequently, the expression of two multidrug resistance proteins, P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1), was analyzed in K562/DOX cells. In addition to P-gp and MRP1, these cells also expressed cluster of differentiation (CD)38 and its active enzyme adenosine diphosphate (ADP)-ribosyl cyclase. The present study also demonstrated that K562/DOX cells responded to cyclic ADP-ribose-mediated increases in intracellular Ca2+. These data indicate that CD38 may participate in the development of drug resistance to doxorubicin in K562 cells. | Authentic |
Text : Immunohistochemical evaluation of serial stored paraffin sections from 42 keratoacanthomas and 11 squamous cell carcinomas demonstrated that skin tumors from UVB-exposed mice showed an inverse relationship (>95%) between p53 protein expression and phospho-Chk1 (Ser317), but not phospho-Chk1 (Ser345) protein expression. Tumors expressing high levels and large areas of p53 protein had no detectable phospho-Chk1 (Ser317), whereas tumors expressing high levels and large areas of phospho-Chk1 (Ser317) protein had no detectable p53. Squamous cell carcinomas that demonstrated heterogeneous p53 and phospho-Chk1 (Ser317) protein expression within the same tumor showed that areas expressing p53 were negative for phospho-Chk1 (Ser317) immunostaining while areas expressing phospho-Chk1 (Ser317) were negative for p53. Similar patterns were observed for keratoacanthomas. These findings were also observed in epidermal areas distant from tumors that demonstrated no detectable phospho-Chk1 (Ser317), but appreciable p53 protein in the basal layer. Tumors from congenic hairless p53 knockout mice had elevated levels of phospho-Chk1 (Ser317) compared to tumors from p53 wild-type SKH-1 controls. After a single exposure to UVB, normal epidermal cells from a p53 knockout mouse expressed a relatively high level of phospho-Chk1 (Ser317) whereas epidermal cells from a p53 wild-type littermate induced p53 protein and expressed a relatively low level of phospho-Chk1 (Ser317). These data illustrate the dynamic regulation of checkpoint function, suggesting that phosphorylation of Chk1 on Serine 317 is regulated by p53 status and that p53 may act as a molecular on/off switch for phosphorylation at this site. | Authentic |
Text : This study was designed to validate the anticancer effects of morusin in human non-small cell lung cancer (NSCLC) cells. Morusin suppressed the cell growth and colony formation in a concentration-dependent manner in H1299, H460 and H292 cells. These anticancer activities were related with apoptosis induction proved by the accumulation of chromatin condensation, PARP cleavage, increase of sub-G1 phage and annexin V-positive cell population. Interestingly, signal transducer and activator of transcription 3 (STAT3) was dephosphorylated by morusin. Morusin suppressed the transcriptional activity of STAT3 and down-regulated the expression of STAT3 target genes. In addition, morusin inhibited the phosphorylation of epithelial growth factor receptor (EGFR), an upstream regulator of STAT3. The docking study showed that morusin directly binds to the tyrosine kinase domain of EGFR. Furthermore, the anticancer effects of morusin were consistently observed in erlotinib-resistant H1975 cells expressing L858R and T790 M mutant EGFR, suggesting that morusin can be used for the advanced NSCLC with acquired resistance to EGFR TKI. Taken together, our results demonstrate that morusin induced apoptosis in human NSCLC cells regardless of EGFR mutation status through inhibition of EGFR/STAT3 activation. | Authentic |
Text : In this study, we aim to examine the association of microRNA-586 (miR-586) with osteosarcoma (OS) cell proliferation, apoptosis, invasion, and metastasis. U2-OS cell lines were divided into 4 groups: an miR-586 group, anti-miR-586 group, control group (empty plasmid) and blank group (no plasmid). qRT-PCR was used to detect miR-586 expression, cell counting kit-8 and EdU assays to detect cell proliferation, flow cytometry to detect cell cycle distribution, Annexin V/PI double staining to detect cell apoptosis, and the Transwell assay to detect cell invasion and metastasis. miR-586 expression was significantly higher in the miR-586 group but significantly lower in the anti-miR-586 group compared with the control and blank groups. Cell proliferation at 2-5 days after cell transfection and the EdU-positive cell number increased obviously in the miR-586 group but decreased clearly in the anti-miR-586 group. In the miR-586 group, cells at G0/G1 stage and apoptosis cells significantly decreased, while cells at G2/M and S stages and invasive and metastatic cells significantly increased compared to the control and blank groups; however, opposite trends were found in the anti-miR-586 group. Downregulation of miR-586 expression in OS may inhibit cell proliferation, invasion and metastasis, and promote cell apoptosis. | Authentic |
Text : Recent studies have discovered a class of circular RNAs (circRNAs), which are dysregulated in various tumors and participate in the regulation of tumor progression. In our research, we aim to research the function of circ-SMAD7 in the progression of glioma. Circ-SMAD7 expression was detected by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) in glioma tissue patients. Pearson's Chi-square test was used to determine the association of circ-SMAD7 expression with several clinicopathological factors. Besides, cell proliferation assay, cell cycle assay, transwell assay, and Matrigel assay were conducted to detect the function of circ-SMAD7 in glioma. In addition, the interaction between circ-SMAD7 and proliferating cell nuclear antigen (PCNA) in glioma was studied by performing qRT-PCR and Western blot assay. Circ-SMAD7 expression was observed in glioma tissues when compared with adjacent samples. The expression of circ-SMAD7 was associated with patients' WHO stage and KPS score. Cell proliferation was inhibited and cell cycle was regulated after circ-SMAD7 was downregulated in glioma cells. Besides, cell migration and invasion were inhibited after circ-SMAD7 was downregulated in glioma cells. In addition, the mRNA and protein expression of PCNA was repressed after circ-SMAD7 was knocked down in glioma cells. Furthermore, PCNA expression level positively correlated to circ-SMAD7 expression level in glioma samples. Our study suggests that circ-SMAD7 promotes proliferation and metastasis of glioma via upregulating PCNA. Circ-SMAD7/ PCNA might be a novel therapeutic strategy in glioma. | Counterfeit |
Text : The study aimed to investigate cyclin-dependent kinase 14 (CDK14) and its co-function with Wnt signaling pathway on cell proliferation, migration and invasion in ovarian cancer. CDK14 expressions were detected by quantitative real-time polymerase chain reaction. The expressions c-Myc, cyclinD1, PFTK1, ki67 and OGT were examined by Western blot. MTT assay was applied to observe cell proliferation after transfection of pEGFP-N1/CDK14-siRNA and pEGFP-N1 into SKOV3 cells, and scratch test and Transwell assay to observe invasion and migration ability. Transfected tumor model in nude mice was established. CDK14 was upregulated in the ovarian cancer tissues and cell lines (both p < 0.05). Expressions of downstream molecules in Wnt signaling pathway as well as the proliferation, invasion and migration ability of the SKOV3 cells were reduced when CDK14 was inhibited (all p < 0.05). The expression of β-catenin in the nucleus was also decreased when CDK14 was inhibited (p < 0.05). In the transfected tumor model of nude mice, the results showed, compared with the pEGFP-N1 group and blank control group, that the expressions of c-Myc, cyclinD1, PFTK1, ki67 and OGT in the pEGFP-N1/CDK14-siRNA group in the transplantation tumor tissues decreased significantly (all p < 0.05). CDK14 suppression-mediated Wnt signaling pathway can inhibit cell proliferation, invasion and migration in ovarian cancer. | Authentic |
Text : Association between allergic conditions and prostate cancer risk has been investigated for many years. However, the results from available evidence for the association are inconsistent. We conducted a meta-analysis to evaluate the relationship between allergic conditions (asthma, atopy, hay fever and "any allergy") and risk of prostate cancer. The PubMed and Embase databases were searched to screen observational studies meeting our meta-analysis criteria. Study selection and data extraction from included studies were independently performed by two authors. Twenty studies were considered eligible involving 5 case-control studies and 15 cohort studies. The summary relative risk (RR) for developing prostate cancer risk was 1.04 (95%CI: 0.92-1.17) for asthma, and 1.25 (95%CI: 0.74-2.10) for atopy, 1.04 (95%CI: 0.99-1.09) for hay fever, 0.96 (95%CI: 0.86-1.06) for any allergy. In the Subgroup and sensitivity analysis, similar results were produced. Little evidence of publication bias was observed. The present meta-analysis of observational studies indicates that no indication of an association between allergic conditions and risk of prostate cancer was found, and the meta-analysis does not support neither the original hypothesis of an overall cancer protective effect of allergic conditions, nor that of an opposite effect in the development of prostate cancer. | Authentic |
Text : The underlying molecular pathogenesis of hepatocellular carcinoma (HCC) remains poorly understood. Mitogen-activated protein kinase kinase 3 (MKK3), has been reported as a novel tumor suppressor in breast cancer. However, its potential suppressive role in HCC has not been evaluated. In the current study, the biologic functions of MKK3 in HCC were investigated and a previously unreported cell cycle regulation mechanism was observed. MKK3 overexpression suppressed HepG2 and PLC‑PRF‑5 cell proliferation and induced cell cycle arrest in the two cell lines. In addition, MKK3 overexpression upregulated the cyclin-dependent kinase inhibitors, p16 INK4A and p15 INK4B in HCC cells. Their negative regulator, Bim‑1, was downregulated following MKK3 overexpression. Moreover, MKK3 activated p38 in HCC cells and SB203580, a p38 inhibitor, reversed the tumor suppressive effect of MKK3. In conclusion, the results identify MKK3 as a tumor suppressor and highlighted the significance of p38 pathway aberration in HCC. | Authentic |
Text : Forkhead box E1 (FOXE1) plays an important role in the development, proliferation and differentiation of thyroid cells. However, the biological functions of FOXE1 in papillary thyroid cancer (PTC) remain unclear. In this study, the level of FOXE1 expression was examined in human PTC tissues and cells. Then, the high expression of FOXE1 was specifically silenced by RNA interference in vitro. Subsequently, FOXE1-shRNA was transfected into PTC cells (TPC-1 and K1). The effects on cell proliferation, migration and invasion were evaluated. In addition, FOXE1 targets were screened by cDNA microarray assays. The correlation between the expression of target gene platelet-derived growth factor A (PDGFA) and clinicopathological features of PTC patients was analysed. FOXE1 is highly expressed in PTC tissues and PTC cell lines. The silencing of FOXE1 significantly promotes PTC cell proliferation, migration and invasion in vitro. The cDNA microarray analyses show that PDGFA is a critical downstream target gene of FOXE1 in PTC cells. It was also observed that PDGFA is negatively regulated by FOXE1 in PTC. The clinical data indicate that the low expression level of PDGFA is correlated with the small size of PTC. Collectively, the results indicate for the first time that high expression of FOXE1 may function as a tumour suppressor in the early stage of PTC and restrain the proliferation, migration and invasion of PTC by negatively regulating PDGFA expression. Thus, FOXE1 could serve as a prognostic biomarker for PTC. | Counterfeit |
Text : Innate immune cells constitute a substantial proportion of the cells within the tumor microenvironment. Besides the contribution of the microenvironment to tumor proliferation and survival, there is direct evidence that interactions between tumor cells and their microenvironment alter sensitivity to anti-cancer agents. Neutrophils, a key player in the innate immune system, have been less studied than many other immune cells regarding their impact on cancer cell response to anti-cancer agents. In our 2D and 3D coculture systems, human neutrophils and differentiated HL60 cells attenuated the sensitivity of various lymphoma cell lines to several anti-cancer agents, including targeted therapies. Neutrophil-induced protection was dependent on cell-cell interaction between CD11b and ICAM-1 expressed by neutrophils and B cells, respectively and was shown to be Mcl-1-dependent. The protective effect of neutrophils was validated in vivo using immune-compromised mice inoculated with human NHL with our without neutrophils then followed by treatment with chemotherapy. Similar findings were made on primary cells purified from patients with chronic lymphocytic leukemia, treated with fludarabine or targeted agents in the presence of autologous neutrophils. In a clinical study, patients with non-Hodgkin's lymphoma with increased neutrophil counts displayed a reduced response rate to therapy. These findings reveal a novel protective mechanism of neoplastic B cells involving innate immune cells which could be pharmacologically targeted to enhance the antitumor effect of therapy. | Authentic |
Text : As acid-base imbalance is involved in many pathological processes, the capability to image tissue pH alterations in the clinic could offer new ways to detect disease and respond to treatment. In this study, the authors show that tissue pH can be imaged in vivo with 11C-labeled bicarbonate (H11CO3-) buffer and positron emission tomography (PET). H11CO3- was produced by on-column NaOH adsorption. Biodistribution of H11CO3- in normal mice was determined. In addition, uptake studies and inhibition experiments of H11CO3- in the S180 fibrosarcoma-bearing mice and the inflammatory mice were investigated with PET imaging. The tumor and inflammatory interstitial pH was measured by a needle pH microelectrode. PET imaging demonstrated the high uptake of H11CO3- in mice tumor tissues and inflammatory tissues, which showed that the average tumor or inflammatory interstitial pH was significantly lower than the surrounding tissue. Administration of sodium bicarbonate in the drinking water increased the measured tumor pH, while the uptake of H11CO3- in mice model tissues had no change. Similarly, administration with ammonium chloride (NH4Cl) decreased the pH, whereas the unchanged uptake of H11CO3- in mice model tissues was also found. However, after administration of acetazolamide, the low uptake of H11CO3- in mice model tissues was observed. H11CO3- solution is an endogenous bicarbonate buffer tracer that can be injected into patients without toxicity. H11CO3- PET can be used clinically to image pathological processes that are associated with acid-base imbalance, such as cancer and inflammation. | Authentic |
Text : Rheumatoid arthritis (RA) is a chronic inflammatory disorder that can, in severe cases, lead to disability. CC chemokine receptor (CCR), an integral membrane protein, has been suggested to play a key role in the RA developmentThis study is to explore the role of CCR5 silencing in inflammatory response, viability, and apoptosis of synovial cells in RA rats by inactivating the mitogen-activated protein kinase (MAPK) signaling pathway. Microarray analysis was conducted to screen out differentially expressed genes from RA-related chips. The rat model was established by injection of siRNA-CCR5 and PD98059 (inhibitor of mitogen-activated protein kinase kinase 1) to evaluate the role of CCR5 silencing in RA, with the involvement of inflammatory response, synovial cell viability, apoptosis, and cycle. CCR5 was predicted to participate in RA by regulating the MARK pathway. In animal experiments, reduction was identified in arthritis index (AI), CCR5 positive expression rate, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase (MMP)-1, and MMP-3 in serum of RA rats after CCR5 siRNA and PD98059 injections. RA rats treated with CCR5 siRNA, and PD98059 presented with inhibition in cell viability, promotion of apoptosis, increase in cell proportion in G0/G1 phase, and shortened the S phase. In addition, the treatment of CCR5 siRNA, and PD98059 resulted in downregulated JNK1, ERK1, p38, Cyclin D1, Cyclin E1, Cyclin B1, and Bcl-2 and upregulated Bax and Cas3. These findings reveal that CCR5 silencing suppresses inflammatory response, inhibits viability, and promotes apoptosis of synovial cells in RA rats by inhibiting MAPK pathway. Therefore, CCR5 silencing may provide a novel therapeutic target for RA. | Counterfeit |
Text : The sensitivity and specificity of biomarkers which have been used in clinical practice for diagnosis of papillary thyroid carcinoma (PTC) are low, it is essential to develop novel diagnostic and prognostic biomarkers for PTC. To explore the expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues and plasma and their associations with the clinical characteristics of PTC. We investigated the expressions of miR-940, miR-15a, miR-16 and IL-23 in plasma and thyroid tissues of PTC, nodular goiter and healthy people with qRT-PCR, and further analyzed the associations between their levels and the clinical characteristics of PTC. Level of IL-23 expression was higher while levels of miR-940, miR-15a and miR-16 expression in the PTC tissues were lower compared with the nodular goiter tissues and perineoplastic thyroid tissues. And the levels of miR-940, miR-15a, miR-16 and IL-23 expression in the PTC tissues were associated with some clinical characteristics of PTC, including bilateral tumor, multicentricity, extrallyroidal invasion, cervical lymph node metastasis, distant metastasis and clinical advanced stages (III/IV). Expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues might be useful biomarkers and promising targets in the diagnosis of papillary thyroid carcinoma. | Authentic |
Text : Gastric cancer is the fourth most common type of cancer and the second highest leading cause of cancer-related deaths worldwide. It has already been established that miR-133a is involved in gastric cancer. In this study, we investigated the molecular mechanisms by which miR-133a inhibits the proliferation of gastric cancer cells. We analyzed the proliferative capacity of human gastric cancer cells SNU-1 using an MTT assay. Cell apoptosis was determined using flow cytometry. The expression levels of ERBB2, p-ERK1/2, and p-AKT in SNU-1 cells were determined using Western blot analysis. To confirm that ERBB2 is a direct target of miR-133a, a luciferase reporter assay was performed. Results showed that miR-133a overexpression inhibited SNU-1 cell proliferation and increased apoptosis. ERBB2 was a direct target of miR-133a, and it was negatively regulated by miR-133a. Interestingly, ERBB2 silencing has a similar impact to miR-133a overexpression, in that it significantly induced apoptosis and inhibited ERK and AKT activation. Our study showed that miR-133a inhibits the proliferation of gastric cancer cells by downregulating the expression of ERBB2 and its downstream signaling molecules p-ERK1/2 and p-AKT. Therefore, miR-133a might be used as a therapeutic target for treating gastric cancer. | Counterfeit |
Text : Non-small cell lung cancer (NSCLC) is a major type of lung cancer. Drug resistance is a enormous obstacle for cancer treatment. Copious microRNAs (miRNAs) have been demonstrated to be implicated in drug resistance in NSCLC. In the present study, RT-qPCR assay revealed that microRNA-1 (miR-1) expression was downregulated in DDP resistant NSCLC tissues and cells. Western blot assay presented a remarkable increase of LC3B-II/LC3B-I ratio and a notable decline of p62 level in DDP resistant NSCLC cells, while these effects were weakened by miR-1. GFP-LC3 puncta experiment showed that ectopic expression of miR-1 induced a noticeable downregulation of GFP-LC3 positive cell percentage in DDP resistant NSCLC cells. Bioinformatical analysis and luciferase assay revealed that autophagy related 3 (ATG3) was a target of miR-1. Also, Western blot and RT-qPCR assays manifested that ATG3 was highly expressed in DDP resistant NSCLC tissues and cells. Additionally, miR-1 inhibited ATG3 expression and ATG3 upregulation abolished miR-1-meidated autophagy inhibition in DDP resistant NSCLC cells. Cell Counting Kit-8 (CCK-8) assay showed that the half maximal inhibitory concentration (IC50 ) of cisplatin (DDP) was reduced in miR-1-enforced DDP resistant NSCLC cells, but was restored following the overexpression of ATG3. Flow cytometry experiments further showed that miR-1 overexpression induced a significant upregulation of apoptotic rate and ATG3 restoration weakened miR-1-induced apoptosis in DDP resistant NSCLC cells. Collectively, our study validated that miR-1 overexpression improved DDP sensitivity of NSCLC cells by inhibiting ATG3-mediated autophagy, providing a potential therapeutic target for easing chemoresistance of anti-tumor drugs. | Authentic |
Text : ω-Hydroxyundec-9-enoic acid (ω-HUA), a plant secondary metabolite, exhibits anti-fungal activity. However, its effect on breast cancer cells is unknown. Here, we investigated the anti- breast cancer activity of ω-HUA and its underlying mechanism. Treatment of human breast cancer cell lines, MDA-MB-231 and MDA-MB-435, with ω-HUA induced apoptotic cell death with increased cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) levels, and p38 and JNK phosphorylation. Inhibition of these mitogen-activated protein kinase (MAPK) pathways using specific inhibitors or siRNA, for p38 and JNK, respectively, blocked the ω-HUA-induced apoptosis in a dose-dependent manner. Moreover, pretreatment of the cells with antioxidant N-acetyl cysteine (NAC) inhibited ω-HUA-induced increased reactive oxygen species (ROS) levels, cleaved caspase-3 and cleaved PARP, and phosphorylated JNK, phosphorylated p38, and increased cell viability and colony-forming ability. MDA-MB-231 xenograft model showed that the ω-HUA-treated group exhibited greater tumor regression and significantly reduced tumor weight compared to that exhibited by the vehicle-administered group. Collectively, ω-HUA-induced intracellular ROS generation induced breast cancer cell apoptosis through JNK and p38 signaling pathway activation, resulting in tumor regression. The results suggested that ω-HUA is an effective supplement for inhibiting human breast cancer growth. | Authentic |
Text : In order to solve the great difficulties in cancer prevention, diagnosis, and treatment, a preparation method of iridium oxide nanocomposites under the microscope was proposed in this paper. Through a retrospective analysis of an experiment, IrOx nanoparticles were prepared by direct hydrothermal hydrolysis and loaded with chemotherapy drug adriamycin to construct nanodrug-loaded complex IrOx@DOX. At the same time, IrOx, as a sound-sensitive agent, can produce ROS under US irradiation, amplify intracellular oxidative stress, accelerate tumor cell death, and finally achieve the effect of SDT chemotherapy synergistic therapy. The experimental results show that IrOx@DOX has the dual response of pH and US, and the inhibition rates are 27%, 57%, and 76%, respectively. At the same time, ultrasound not only can enhance the uptake of nanoparticles by cells but also can promote the release of DOX in cells, which provides a basis for subsequent SDT chemotherapy synergistic therapy. Conclusion. Iridium oxide nanocomposite DOX combined with SDT can obtain a good therapeutic effect, which has positive feedback on the efficacy of chemotherapy and the therapeutic effect of cancer surgery. | Authentic |
Text : Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor, which can cause significant bone destruction at the epiphysis of long bones. Recent studies have demonstrated that norcantharidin (NCTD) can inhibit the proliferation and migration of various human cancer cells, but the role of NCTD in GCTB has not previously been evaluated. The aim of this study was to explore the nature of the anti-cancer effects of NCTD in GCTB and to elucidate the biomolecular mechanisms responsible for these effects. Primary stromal cell cultures, representing the main neoplastic component of GCTB, were used for cell-based experiments. Firstly, the anti-cancer effects of NCTD on GCTB stromal tumor cells were investigated by CCK-8 assay, flow cytometry and transwell invasion assay. Next, microRNA (miRNA) microarray and quantitative reverse transcription PCR (qRT-PCR) analyses were performed to examine and verify altered expression of miRNAs associated with NCTD treatment. Subsequently, the GCTB stromal cells were transfected with miR-30a inhibitor to confirm its involvement in the observed anti-cancer effects of NCTD. Luciferase reporter assays were carried out to identify the target gene of miR-30a. Moreover, changes in the expression of protein markers of AKT signaling were measured by Western Blot analysis. The results demonstrated that NCTD treatment could inhibit cell proliferation, block the cell cycle process and induce cell apoptosis in GCTB stromal cells. An inhibitory effect of NCTD on GCTB stromal cell invasion through inhibition of epithelial mesenchymal transition (EMT) was also observed. Expression of miR-30a was significantly upregulated by NCTD treatment and miR-30a knockdown significantly reversed the anti-tumor effects of NCTD against GCTB stromal cells. Of note, metadherin (MTDH), a novel oncogene which modulates the AKT pathway, was identified as a direct target of miR-30a in GCTB stromal cells. Further data showed that miR-30a could negatively regulate the expression of MTDH and the AKT pathway in GCTB stromal cells. Importantly, MTDH expression was found to be inversely correlated with miR-30a expression in clinical GCTB specimens. Moreover, NCTD treatment effectively suppressed the AKT signaling pathway as demonstrated by downregulation of phosphorylated-Akt S473 (p-Akt S473), p-Akt (T308), phosphorylated-glycogen synthase kinase (GSK)3β (p-GSK3β) and c-Myc, whilst miR-30a inhibition re-activated the AKT signaling pathway in GCTB stromal cells. Our findings demonstrate that NCTD can inhibit cell proliferation and metastasis of GCTB stromal cells in vitro, via modulating the miR-30a/MTDH/AKT signaling axis. This suggests that NCTD has potential as a novel therapeutic treatment for GCTB. | Authentic |
Text : The present study aimed to investigate the effect of dihydroartemisinin on the proliferation of chemotherapy‑resistant C6 rat glioma cells. The results revealed that incubation of C6 glioma cells with a range of dihydroartemisinin concentrations for 48 h led to a significant (P<0.02) reduction in the cell number. There was a ‑0.8-fold reduction in the cell count following treatment with 20 µM dihydroartemisinin when compared with the control cultures. Analysis of DNA synthesis using bromodeoxyuridine (BrdU) staining demonstrated a reduction in the BrdU‑labeling index (LI) following treatment with 20 µM dihydroartemisinin. There was a 6‑fold reduction in the BrdU‑LI compared with the control cultures. Incubation of the C6 glioma cells with dihydroartemisinin led to a concentration dependent reduction in the level of cyclic adenosine 3',5'‑monophosphate following 48 h. The percentage of apoptotic cells in the cultures incubated with 20 µM dihydroartemisinin was 54.78% compared with 2.57% in the control cultures. Incubation of the C6 glioma cells with dihydroartemisinin for 48 h led to a reduction in the percentage of cells in G2/M phase with an increase in G0/G1 phase. The control cells exhibited spindle‑shaped morphology and were actively undergoing mitosis following 48 h of culture. The morphological characteristics of the cells treated with dihydroartemisinin were demonstrated to be round with small surface projections. Therefore, treatment of glioma cells with dihydroartemisinin exhibited an antitumor effect by the induction of apoptosis. Therefore, dihydroartemisinin should be evaluated further in the animal models for the treatment of glioma. | Authentic |
Text : Keloids are a type of benign hyperplasia that cause dermatologic dysfunction and esthetic deformity by invading adjacent normal tissues. Little is known about their etiology, therefore, they are a challenge to treat using plastic surgery. In a previous study, it was demonstrated that the expression of the long non-coding RNA CACNA1G-AS1 (CAS1) is high in keloid tissue, suggesting that CAS1 is involved in keloid formation. In the present study, the aim was to identify potential keloid target proteins by exploring CAS1 biological function during cell proliferation and migration, cytokine secretion, collagen secretion and the control of calcium channel protein expression in human keloid fibroblasts. Three biopsy samples were collected from each patient with keloids at The Peking Union Medical College Hospital, which were then used to investigate the role of CAS1 in cell proliferation and migration. CAS1 silencing was also carried out using small interfering RNA; cell factors, collagen and calcium channel protein levels were compared with control cells. The interference of CAS1 expression reached 50% compared with the control group. CACNA1G and type I collagen expression was significantly downregulated by CAS1 knockdown, while the expression of transforming growth factor-β and type III collagen was not affected. Wound healing time was longer in the CAS1-knockdown group, but there was no visible change in cell proliferation. In conclusion, CAS1 appeared to promote calcium channel protein and type I collagen expression, and to have a positive effect on cell migration in human keloid fibroblasts. Therefore it has potential as a novel therapeutic target for keloids. | Authentic |
Text : Radiotherapy does not show good efficacy against laryngeal cancer due to radioresistance. Cancer stem cells (CSCs) are considered among the causes of radioresistance. Inhibition of glucose transporter-1 (GLUT-1) using GLUT-1 small interfering RNA (siRNA) may enhance the radiosensitivity of laryngeal cancer cells, but the underlying cellular mechanisms remain unclear. The CD133+-Hep-2R cell line was established with repeated irradiation and magnetic-activated cell sorting. The effects of irradiation on CD133+-Hep-2R cells were examined by CCK-8 assay, Transwell assay, quantitative real-time polymerase chain reaction (RT-PCR), and Western blotting. The effects of GLUT-1 siRNA on the radiosensitivity of CD133+-Hep-2/2R cells were examined by RT-PCR, Western blotting, CCK-8 assay, colony formation assay, and Transwell assay in vitro and in a xenograft tumor model in nude mice. The cellular mechanism of enhanced radiosensitivity associated with GLUT-1 siRNA was investigated. The cell cycle and apoptosis rate were analyzed by flow cytometry, and the repair capability was examined by determining the levels of RAD51 and DNA-PKcs. CD133+-Hep-2/2R cells showed stronger proliferation, lower apoptosis rate, lower percentage of G0/G1 phase cells, higher percentages of S and G2/M phase cells, and higher expression levels of GLUT-1 than Hep-2/2R cells. Transfection with GLUT-1 siRNA inhibited the proliferation and invasive capability of CD133+-Hep-2R cells by inhibiting GLUT-1 expression, which also caused a redistribution of the cell cycle (higher proportion of cells in the G0/G1 phase and lower proportion in the S and G2/M phases), increased the apoptosis rate, and reduced DNA repair capability by suppressing RAD51 and DNA-PKcs expression. The results of this study suggest that GLUT-1 siRNA can enhance the radiosensitivity of CD133+-Hep-2R cells by inducing a redistribution of cell cycle phases, inhibiting DNA repair capability, and increasing apoptosis. Inhibition of GLUT-1 may have therapeutic potential for interventions to increase the radiosensitivity of laryngeal CSCs. | Authentic |
Text : Patients diagnosed with triple negative breast cancer (TNBC) have limited treatment options and often suffer from resistance and toxicity due to chemotherapy. We previously found that depleting calcium and integrin-binding protein 1 (CIB1) induces cell death selectively in TNBC cells, while sparing normal cells. Therefore, we asked whether CIB1 depletion further enhances tumor-specific killing when combined with either the commonly used chemotherapeutic, docetaxel, or the cell death-inducing ligand, TRAIL. We targeted CIB1 by RNA interference in MDA-MB-436, MDA-MB-231, MDA-MB-468, docetaxel-resistant MDA-MB-436 TNBC cells and ME16C normal breast epithelial cells alone or combination with docetaxel or TRAIL. Cell death was quantified via trypan blue exclusion using flow cytometry and cell death mechanisms were analyzed by Western blotting. Cell surface levels of TRAIL receptors were measured by flow cytometry analysis. CIB1 depletion combined with docetaxel significantly enhanced tumor-specific cell death relative to each treatment alone. The enhanced cell death strongly correlated with caspase-8 activation, a hallmark of death receptor-mediated apoptosis. The death receptor TRAIL-R2 was upregulated in response to CIB1 depletion, which sensitized TNBC cells to the ligand TRAIL, resulting in a synergistic increase in cell death. In addition to death receptor-mediated apoptosis, both combination treatments activated a non-apoptotic mechanism, called paraptosis. Interestingly, these combination treatments also induced nearly complete death of docetaxel-resistant MDA-MB-436 cells, again via apoptosis and paraptosis. In contrast, neither combination treatment induced cell death in normal ME16C cells. Novel combinations of CIB1 depletion with docetaxel or TRAIL selectively enhance naive and docetaxel-resistant TNBC cell death while sparing normal cell. Therefore, combination therapies that target CIB1 could prove to be a safe and durable strategy for treatment of TNBC and potentially other cancers. | Authentic |
Text : The goal of our study was to assess the prognostic impact of the necroptosis relative protein RIPK1 genetic polymorphism in ischemia-reperfusion injury and survival after hepatectomy in hepatocellular carcinoma (HCC) patients. In this study, expression of RIPK1 and its genetic polymorphism(rs2272990) were examined in plasma of 44 HCC patients. All these patients were undergoing partial hepatectomy. The prognostic values of RIPK1 genetic polymorphism for tumor development and survival, and ischemia-reperfusion injury after hepatectomy were further determined. Plasma RIPK1 expressions were significantly increased in HCC patients, compared to the healthy control group. Totally 19 patients have the GA + AA genotype in the RIPK1 rs2272990 SNP site and 25 have GG genotype. There were no statistically significant intergroup differences observed in age, gender, AFP value, HBV positive, tumor size or cirrhosis. GG genotype had positive correlation with TNM classification (p= 0.033) and lymphatic metastasis (p= 0.027) and was significantly associated with severe hepatic ischemia-reperfusion injury and decreased survival rate after hepatectomy. In conclusion, the RIPK1 polymorphism is an indicator of hepatic injury and a novel prognostic biomarker for tumor development and survival of HCC recipients after hepatectomy. | Authentic |
Text : Lung cancer is a commonly diagnosed disease with poor prognosis. Novel therapeutic targets and deep understanding of the regulatory mechanisms in lung cancer are of great importance. We aimed to figure out the functional roles of lncRNA-activated by transforming growth factor-β (ATB) in A549 cells as well as the underlying molecular mechanisms. ATB was non-physiologically expressed in A549 cells after cell transfection. Then, cell proliferation, expressions of proteins related to proliferation and epithelial-mesenchymal transition (EMT), migration, and invasion were measured by BrdU incorporation assay, Western blot analysis, and Transwell assay, respectively. Afterwards, miR-494 expression in transfected A549 cells was determined by quantitative reverse transcription PCR. Meanwhile, effects of miR-494 overexpression on ATB-overexpressed cells were assessed. Finally, the phosphorylation levels of AKT and key kinases in the Janus-activated kinase (JAK)/signal transducer and activator of transcription-3 (STAT3) pathway were detected by Western blot analysis. ATB overexpression promoted proliferation, migration, and invasion of A549 cells. Meanwhile, EMT of A549 cells was also enhanced. ATB silence showed the opposite influence. Expression of miR-494 was negatively regulated by ATB. Following experiments showed ATB-induced alterations of proliferation, migration, invasion, and EMT were all reversed by miR-494 overexpression. Finally, we proved that ATB increased phosphorylated levels of AKT, JAK1, and STAT3, and those increases were all reversed by miR-494 overexpression. We interestingly figured out that ATB promoted proliferation, migration, invasion, and EMT through down-regulating miR-494 in A549 cells. Moreover, ATB might activate AKT and the JAK/STAT3 pathway via down-regulating miR-494. | Authentic |
Text : Lymph node status is one of the most important prognostic factors for uterine cervical cancer. Sentinel lymph node (SLN) biopsy has emerged as a potential alternative to systematic lymphadenectomy for the lymph node mapping in such patients. However, the SLN metastasis detection via SLN biopsy in early-stage cervical cancer remains controversial. The current study is aimed at investigating the feasibility and accuracy of combined tracer method for localization of SLN in initial stages of cervical cancer and to evaluate the clinical value of SLN biopsy in replacing pelvic lymph node resection. We retrospectively reviewed 348 cases who were admitted to the Department of Gynecologic Oncology, Shandong Provincial Cancer Hospital, China, between February 2003 and June 2018 with FIGO stage IA2 to IIA2 cervical cancer and undergone through SLN biopsy. Methylthioninium chloride was injected in combination with 99mtechnetium-labeled sulfur colloid prior to surgery to these patients. SLNs were identified intraoperatively, excised, and subsequently submitted to fast frozen section. The detection rates, accuracy, sensitivity, coincidence rate, false negative rate, and negative predictive values of these cases were estimated, and the follow-up outcomes were carefully observed. Chi squared test or Fisher's exact test was employed for a comparison of the categorical variables. Univariate and multivariate Cox proportional hazard models were used for estimation of relationships between overall survival (OS) and disease-free survival (DFS) and prognostic factors. The total detection rate of SLN was 97.1% (338/348), and identification of bilateral SLN was successful in 237 patients (70.1%). The patient's tumor size, FIGO stage, lymph node metastasis, and depth of invasion had statistically significant differences in SLN detection rates. The detection rate had inverse relation with tumors size (>4 cm), invasive depth > 2/3, lymph node positive, late staging, and preoperative radiotherapy. 117 positive SLNs were detected in 73 patients. The negative predictive value, sensitivity, false negative rate, and coincidence rate and were 97.7%, 92.4%, 7.6%, and 95.4%, respectively. In patients whose tumor size were ≦ 4 cm, the false negative rate was 4.55% (2/44), whereas it was 0 in patients with tumor size≦2 cm. The respective 1, 3, and 5-year OS was 100%, 94.8%, and 91.8%, respectively, whereas DFS rate for 1, 3, and 5 years was 96.7%, 92%, and 89.6%, respectively. The lymph node was positive, tumor size, the depth of invasion, and staging were statistically different from the recurrence rate and survival rate of patients (p < 0.05). When tumor metastasis exceeded SLN, the recurrence rate was significantly increased, and survival rate is significantly reduced (p < 0.05, p < 0.01, p < 0.05, respectively). The identification of SLN combined with 99mtechnetium-labeled sulfur colloid and methylthioninium chloride has a good accuracy and is safe for the assessment of the status of pelvic nodes in patients with initial stage cervical cancer. Nuclide as a tracer has low dependence on objective conditions and doctors' technology and has a good detection rate. In our study, we believe that SLN biopsy is feasible when the tumor is ≦ 4 cm. Large scale clinical trials are required in China expand the sample size and validate the results of this study. | Authentic |
Text : The effect of miR-182 on the expressions of CRR9 in laryngeal squamous cell carcinoma (LSCC) cells, and the impact on invasion and metastasis of LSCC were investigated in the present paper. The expressions of miR-182 in LSCC tissue and cell line were detected by RT-qPCR. MTT assay and Annexin V staining were used to detect the effects of miR-182 on tumor cells proliferation. Target gene prediction and screening, and luciferase reporter assay were designed to verify downstream target genes of miR-182. The mRNA and protein expressions of CRR9 were detected by qRT-PCR and Western blot. Finally, the expressions of CRR9 were measured by transfecting cells with miR-182 in mice. Compared with normal tissue and cell, the expressions of miR-182 in tumor tissues and cells were much lower. Over-expressions of miR-182 can increase apoptosis rate. Luciferase reporter assay revealed that CRR9 was a downstream gene of miR-182. Reintroduction of CRR9 abolished miR-182-induced LSCC cell growth inhibition. In animal models, over-expressions of miR-182 can reduce tumor weight and promote apoptosis. miR-182 can inhibit the proliferation of LSCC cells by directly inhibiting the expressions of CRR9, thereby suppressing the occurrences and developments of LSCC. | Counterfeit |
Text : PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells. A phase III clinical trial, Checkmate 143, reported that nivolumab, which targets PD-1, did not demonstrate survival benefits compared with bavacizumab in recurrent glioblastoma patients. Thus, the combination of a PD-1/PD-L1 checkpoint blockade with RT, TMZ, antibodies targeting other inhibitory or stimulatory molecules, targeted therapy, and vaccines may be an appealing solution aimed at achieving optimal clinical benefit. There are many ongoing clinical trials exploring the efficacy of various approaches based on PD-1/PD-L1 checkpoint blockades in primary or recurrent glioblastoma patients. Many challenges need to be overcome, including the identification of discrepancies between different genomic subtypes in their response to PD-1/PD-L1 checkpoint blockades, the selection of PD-1/PD-L1 checkpoint blockades for primary versus recurrent glioblastoma, and the identification of the optimal combination and sequence of combination therapy. In this review, we describe the immunosuppressive molecular characteristics of the tumour microenvironment (TME), candidate biomarkers of PD-1/PD-L1 checkpoint blockades, ongoing clinical trials and challenges of PD-1/PD-L1 checkpoint blockades in glioblastoma. | Authentic |
Text : 5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than five- and sixfolds, respectively, as assessed by MTT assay. We show that this is due to global alterations in nucleotide metabolism, including elevated expression of thymidylate synthase and thymidine kinase 1 (established 5-FU resistance mechanisms), which likely result in an increase in intracellular dTTP pools and a "dilution" of 5-FU anabolites. Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine. Indeed we show that metformin pre-treatment greatly increases gemcitabine toxicity and DNA fragmentation in comparison to gemcitabine alone. Taken together, our findings show that metformin alters nucleotide metabolism in OSCC cells and while responsible for inducing resistance to 5-FU, it conversely increases sensitivity to gemcitabine, thereby highlighting metformin and gemcitabine as a potentially novel combination therapy for OSCC. | Authentic |
Text : Homeobox B5 (HOXB5), a member of the HOX gene family, has been shown to play an important role in tumor progression. However, the expression and functional role of HOXB5 in human non-small cell lung cancer (NSCLC) have not been defined. Thus, the purpose of this study was to elucidate the expression and functional role of HOXB5 in human NSCLC. Our results showed that HOXB5 expression was elevated in human NSCLC tissues and cell lines. The in vitro experiments demonstrated that knockdown of HOXB5 inhibited proliferation, migration, and invasion and prevented the EMT phenotype in NSCLC cells. In vivo experiments indicated that knockdown of HOXB5 attenuated the growth of NSCLC xenografts in vivo. Furthermore, knockdown of HOXB5 suppressed the protein expression levels of β-catenin and its downstream targets c-Myc and cyclin D1 in A549 cells. Taken together, for the first time we have shown that knockdown of HOXB5 significantly inhibited NSCLC cell proliferation, invasion, metastasis, and EMT, partly through the Wnt/β-catenin signaling pathway. These findings suggest that HOXB5 may be a novel therapeutic target for the treatment of NSCLC. | Authentic |
Text : Peritoneal metastasis from colorectal cancer (CRC) is related to poor prognosis. Intraperitoneal chemotherapy is an efficient method to treat peritoneal metastasis (PM); however, the outcomes remain unsatisfactory. The present study aimed to investigate the antitumor activity of lobaplatin and its role in intraperitoneal chemotherapy. The findings showed that the proliferation of CRC was inhibited in a dose-dependent manner when DLD1 and HCT116 cells were treated with various concentrations of lobaplatin (0, 6.3, 12.5, 25, 50, and 100 μg/mL, respectively). Flow cytometry and Western blot analysis confirmed that lobaplatin affected CRC cells by inducing apoptosis and modulating the caspase family. In the animal study, nude mice were injected with DLD1 cells and divided into three groups. Lobaplatin was injected intraperitoneally to simulate intraperitoneal chemotherapy. Group A was the control group treated with PBS. Group B was injected with DLD1 and treated with lobaplatin simultaneously, while group C was treated with lobaplatin 1 week after cell injection. The results showed that group A harbored maximal tumors on the peritoneal surface, while group B had the least number (9.2 ± 1.3 and 0.4 ± 0.5, respectively P < 0.01). These findings indicated that lobaplatin suppressed the tumor growth as an intraperitoneal chemotherapy agent and achieved a satisfactory therapeutic effect at an early stage. Further blood test and tissue staining did not reveal any liver and kidney toxicity that was induced by lobaplatin. In conclusion, lobaplatin could be an effective and safe agent for CRC treatment, thereby commissioning a novel strategy in intraperitoneal chemotherapy for patients with peritoneal metastasis. | Authentic |
Text : Cyclooxygenase-2 (COX-2) is frequently overexpressed and enhances colorectal cancer (CRC) tumorigenesis, including cancer stem cell (CSC) regulation. Accordingly, nonsteroidal anti-inflammatory drugs (NSAIDs), inhibiting COX-1/2 activity, are viewed as potential drugs for CRC treatment. Accumulated evidence indicates that celecoxib has the most potency for antitumor growth among NSAIDs and the underlying mechanism is only partly dependent on COX-2 inhibition. However, the potency of these NSAIDs on CSC inhibition is still not known. In this study, we found that among these NSAIDs, celecoxib has the most potency for CSC inhibition of CRC cells, largely correlating to inhibition of c-Met, not COX-2. Further analysis reveals that c-Met activity was required for basal CSC property. Silence of c-Met blocked whereas overexpression of c-Met enhanced the celecoxib-inhibited CSC property. Collectively, these results not only first elucidate the mechanism underlying celecoxib-inhibited CSC but also indicate c-Met as a critical factor for the CSC property of CRC cells. | Authentic |
Text : Ampelopsin has displayed anticancer activity in several types of cancers. However, no evidence has been reported for the direct effect of ampelopsin on ovarian cancer cell migration and invasion, and the underling mechanisms have not yet been clearly established. The aim of the present study was to investigate the influence of ampelopsin on the migration and invasion of ovarian cancer. Proliferation and viability of the ovarian cancer cells were detected by MTT assay. Migration and invasion of the cells were detected, respectively, by scratch wound healing assay and Transwell assay. The expression levels of epithelial-to-mesenchymal transition (EMT) markers were detected at the protein level after stimulation with ampelopsin. Then, the expression levels of NF-κB and p-IκBα were detected with western blot analysis. Meanwhile, an inhibitor of NF-κB was used to investigate the effect of ampelopsin. Finally, the expression of Snail was also detected. Proliferation, migration and invasion of the A2780 cells were all inhibited following the application of ampelopsin. Ampelopsin upregulated E-cadherin and downregulated N-cadherin and vimentin in a concentration- and time-dependent manner. Ampelopsin also exerted its ability to suppress the nuclear translocation of the NF-κB pathway. Administration of the inhibitor BAY11-7082 confirmed the roles of NF-κB in the expression of EMT markers and its transcription factor. These results demonstrated that ampelopsin inhibited EMT and reduced the invasion of ovarian cancer cells via the NF-κB/Snail pathway. | Authentic |
Text : Invasive breast cancer (IBC) is a kind of malignant tumor in which cancer cells have broken through the basement membrane of breast ducts or lobular acini and invaded the stroma. Although ultrasound elastography score (UES) has shown unique advantages in the diagnosis of IBC, its value in the prognosis is not clear. Here, we explored the correlation of UES with IBC and biological prognostic factors. The datum of 86 patients with suspected IBC from January 2018 to December 2021 was collected. UE was applied in the examination of all patients. The lesion tissue of the malignant group was punctured to detect and analyze the expression of biological prognostic factors, including estrogen receptor (E receptor), progesterone receptor (P receptor), and human epidermal growth factor 2 (HER factor 2) and Ki67. The differences in UES under different biological prognostic factors were compared. The receiver operating characteristic (ROC) curve was applied to analyze the diagnostic value of UES of IBC and the expression of biological prognostic factors. Based on the pathological diagnosis results, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of UES in the diagnosis of IBC were analyzed. The correlation of UES with IBC and biological prognostic factors was analyzed by multiple linear regression and Spearman method. ROC analysis showed that the area under the curve of UES for diagnosing IBC and evaluating the expression of P receptor, HER factor 2, and Ki67 were 0.877, 0.704, 0.763, and 0.820, respectively (P＜0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of UES when diagnosing IBC were 92.42%, 90.00%, 91.86%, 96.83%, and 78.26%, respectively. The UES of E receptor expression (positive and negative group) showed no obvious variance (P > 0.05). The UES of P receptors (positive and negative), HER factor 2 (positive and negative), and Ki67 (high and low expression) showed obvious differences (P < 0.05). Multiple linear regression and Spearman indicated UES was significantly correlated with the expression of P receptor, HER factor 2, and Ki67 (P＜0.05). UES has a certain diagnostic value for IBC and is significantly correlated to the expression of P receptor, HER factor 2, and Ki67, which is helpful for evaluating the prognosis of patients with IBC. | Authentic |
Text : The aim of the present study was to compare the effectiveness of transarterial chemoembolization (TACE), TACE combined with Jie-du granules (JD), and TACE combined with sorafenib (SOR) for treating patients with unresectable hepatocellular carcinoma (HCC). For this purpose, we conducted a retrospective analysis of data from 266 consecutive patients with unresectable HCC who underwent TACE treatment at the Shanghai Hospital and Eastern Hepatic Surgery Hospital between Jan 2009 and Dec 2010. We prospectively analyzed patient survival and progression times as well as independent predictors, within a follow-up period of 86 months. Patients were divided into TACE-JD (n = 75), TACE-SOR (n = 124) and TACE (n = 67) groups. Median overall survival (OS) times being: TACE-JD, 21.43 months; TACE-SOR, 23.23 months; TACE, 13.97 months (TACE-SOR vs TACE, P < 0.001; TACE-SOR vs TACE-JD, P = 0.852; TACE-JD vs TACE, P < 0.001). The median times to progression (TTP) were as follows: TACE-JD, 8.67 months; TACE-SOR, 5.37 months; TACE, 4.57 months (TACE-SOR vs TACE, P = 0.479; TACE-SOR vs TACE-JD, P < 0.001; TACE-JD vs TACE, P < 0.001). Independent predictors of OS were treatment allocation, Child-Pugh class large tumor, albumin and extrahepatic metastasis. These findings show that patients with unresectable HCC who were administered TACE-JD survived significantly longer compared with those administered TACE or TACE-SOR. | Authentic |
Text : Plant-derived phytonutrients have emerged as health enhancers. Tocotrienols from the vitamin E family gained high attention in recent years due to their multi-targeted biological properties, including lipid-lowering, neuroprotection, anti-inflammatory, antioxidant, and anticancer effects. Despite well-defined mechanism of action as an anti-cancer agent, their clinical use is hampered by poor pharmacokinetic profile and low oral bioavailability. Delivery systems based on nanotechnology were proven to be advantageous in elevating the delivery of tocotrienols to tumor sites for enhanced efficacy. To date, preclinical development of nanocarriers for tocotrienols include niosomes, lipid nanoemulsions, nanostructured lipid carriers (NLCs) and polymeric nanoparticles. Active targeting was explored via the use of transferrin as targeting ligand in niosomes. In vitro, nanocarriers were shown to enhance the anti-proliferative efficacy and cellular uptake of tocotrienols in cancer cells. In vivo, improved bioavailability of tocotrienols were reported with NLCs while marked tumor regression was observed with transferrin-targeted niosomes. In this review, the advantages and limitations of each nanocarriers were critically analyzed. Furthermore, a number of key challenges were identified including scale-up production, biological barriers, and toxicity profiles. To overcome these challenges, three research opportunities were highlighted based on rapid advancements in the field of nanomedicine. This review aims to provide a wholesome perspective for tocotrienol nanoformulations in cancer therapy directed toward effective clinical translation. | Authentic |
Text : An increased risk of cardiovascular complications is reported in survivors of childhood acute lymphoblastic leukemia (ALL). Early identification of impaired vascular health may allow for early interventions to improve outcomes. The study was conducted to assess the endothelial dysfunction in ALL survivors using a new marker, serum endocan, and measurement of the mean common carotid arteries intima media thickness (cIMT). A case-control study was conducted on 100 childhood ALL survivors (aged 6-18 years), with 80 healthy age and sex-matched children as a control group. Lipid profile, hepatitis markers, and serum ferritin where measured, in addition to the measurement of serum endocan. and cIMT by B-mode high-resolution ultrasonography for all study participants. Triglycerides, total cholesterol, post prandial glucose, and serum ferritin were significantly higher in ALL survivors than controls (p < 0.05). Dyslipidemia was detected in 6% of ALL survivors. ALL survivors showed statistically higher serum endocan levels (470.41 ± 556.1 ng/l, versus, 225.94 ± 185.2 ng/l, respectively) and increased cIMT levels compared with the control group (0.650 ± 0.129 mm versus 0.320 ± 0.095 mm, respectively) p < 0.05. Serum endocan was positively correlated with cIMT and blood cholesterol. The survivors of childhood ALL demonstrated an elevated level of serum endocan and increased cIMT. These can be used as predictors of endothelial dysfunction, and, as a consequence, the risk of developing premature atherosclerosis. | Authentic |
Text : Colorectal cancer (CRC) is the fourth most common cause of cancer and mortality worldwide and is the third most common cancer in men and women. Surgery, radiotherapy, and chemotherapy are conventionally used for the treatment of colorectal cancer. However, these methods are associated with various side effects on normal cells. Thus, new studies are moving towards more effective and non-invasive methods for treatment of colorectal cancer. Targeted therapy of CRC is a promising new approach to enhance the efficiency and decrease the toxicity of the treatment. In targeted therapy of CRC, antibody fragments can directly inhibit tumor cell growth and proliferation. They also can act as an ideal carrier for targeted delivery of anticancer drugs. In the present study, the structure and function of different formats of antibody fragments, immune-targeted therapy of CRC using antibody fragments will be discussed. | Authentic |
Text : The present study investigated the expression and potential influence of SHC SH2 domain‑binding protein 1 (SHCBP1) in gastric cancer (GC) cells. SHCBP1 is closely related to cell proliferation and cell cycle progression, but its role in GC remains unclear. The TCGA database revealed that SHCBP1 is highly expressed in GC tissues. Furthermore, SHCBP1 was revealed to be highly expressed in GC cell lines MGC‑803 and SGC‑7901 cells, and downregulation of SHCBP1 significantly inhibited GC cell proliferation. Furthermore, SHCBP1 expression promoted cell cycle progression and inhibition of apoptosis. Since the CDK4, cyclin D1 and caspase family proteins play important roles in cell cycle and apoptosis regulation, it was examined whether there was an association between SHCBP1 and these signaling pathways in GC. Our results revealed that SHCBP1 promoted cell cycle progression by regulating the CDK4‑cyclin D1 cascade and suppressed caspase‑3, caspase PARP‑dependent apoptotic pathways. Cell invasion and metastasis experiments also revealed that SHCBP1 promoted tumor growth and invasiveness. These tumor‑promoting functions of SHCBP1 may provide a potential molecular basis for the diagnosis and targeted therapy of GC. | Authentic |
Text : Chemotherapy is the predominant treatment option for patients with breast cancer. Selection of patients according to biomarker will improve chemotherapy efficacy. In the present study, we examined the relations of the expression of candidate genes and 21-recurrence score (RS) results to patients' demographic characteristics, histopathological factors, and outcomes. A total of 146 patients were enrolled in this study. The patients underwent 21-gene RS testing. In addition, expressions of candidate genes, TYMS, RRM1, TUBB3, TOP2A, PTEN, were detected. Information was obtained on age, tumor size, TMN stage, tumor grade, and status of Ki-67, HER2, ER and PR. The treatment information on the type of endocrine therapy was also obtained. Results clearly showed that the 21-gene RS significantly correlated with the TNM stage of breast cancer (P = 0.047). The RS also correlated with the number of sentinel lymph node (P = 0.038). The pathological type of tumors was strongly associated with the expression of RRM1 (P < 0.015), and slightly correlated with TYMS (P = 0.095) and tumor size (P = 0.061). Further analysis showed that TYMS and RRM1 were two independent factors affecting the disease progression of patients. Besides, for HER-2 stain, staining of grade 2 or above significantly increased the risk of disease progression. Our studies showed that TNM stage and sentinel lymph node were important clinical parameters correlated with 21-gene RS results. Also, RRM1, TYMS and HER2 expressions were independent factors associated with disease progression in breast cancer patients. Future study is warranted to investigate the usefulness of these genes in treatment efficacy. | Authentic |
Text : Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the malignant progression of a number of human cancers. However, the roles of SPARC in lung squamous cell carcinoma (LSCC) remain elusive. In this present study, we first detected SPARC expression and investigated the relationship between SPARC expression and the clinicopathological attributes of LSCC patients. Then we constructed SPARC-overexpression model in LSCC cell line to explore the characteristics of SPARC in LSCC development both in vitro and in vivo. The data demonstrated a remarkably higher level of SPARC in LSCC tissues than in corresponding non-cancerous tissues and elevated SPARC expression was significantly correlated with poor outcome in LSCC patients. Moreover, a serial of phenotypic experiments indicated that SPARC overexpression substantially facilitated the growth and inhibited the apoptosis in LSCC cells and xenografts. Taken together, our results suggest that SPARC is a novel prognostic marker for LSCC prognosis and SPARC significantly promotes LSCC tumorigenesis. Targeting SPARC may provide a novel therapeutic strategy for LSCC management. | Authentic |
Text : To grab the possible impact of lncRNA-SVUGP2 in the biology and process of non-small cell lung cancer (NSCLC). Sixty paired NSCLC tumour and the adjacent non-tumour lung tissues were collected for detection of lncRNA-SVUGP2. lncRNA-SVUGP2 expression in NSCLC cells (SK-MES-1, A549, SPC-A1, and NCI-H1975) was also detected. lncRNA-SVUGP2 was overexpressed and depressed in A549 and H1975 cells, and the effects of lncRNA-SVUGP2 dysregulation on cell biological performances including viability, colony formation, apoptosis, migration and invasion were grabbed. Furthermore, the regulatory association of lncRNA-SVUGP2 vs. EZH2 in H1975 cells, as well as the association between lncRNA-SVUGP2 and Wnt/β-catenin pathway, was explored. lncRNA-SVUGP2 was depressed in NSCLC tissues and cells. Overexpression of lncRNA-SVUGP2 depressed proliferation, induced apoptosis, and suppressed migration and invasion of A549 and H1975 cells. In addition, lncRNA-SVUGP2 was repressed by EZH2 and was inversely correlated with EZH2 levels in H1975 cells. Repression of lncRNA-SVUGP2 potentially participated in the oncogenic function of EZH2. Besides, overexpression of lncRNA-SVUGP2 depressed the briskness of Wnt/β-catenin signal in H1975 cells. Our data reveal that lncRNA-SVUGP2 is under-expressed in NSCLC cells and the reduced expression of lncRNA-SVUGP2 may enhance the development and process of NSCLC by interacting with EZH2 and activating Wnt/β-catenin pathway. | Authentic |
Text : In order to further curb the damage to the ecological environment from the perspective of legal synergistic supervision, a synergistic analysis method between the ecological protection environmental law and the ecological Civil Code is proposed. Coordinated supervision, with the new Civil Code as the research background, from the perspective of interpretation, explores the solution to the problem of "ecological environmental damage" in the newly promulgated Civil Code for behavior that damages the ecological environment. The research results believe that, from the perspective of rights, environmental rights should be regarded as the concentrated expression of rights in the sense of private law in the ecological environment law. Article 1234 of the Tort Liability Section stipulates that "the state-specified agency or the law-specified organization" as the representative of environmental public interests proposes damage. The request resolves the legitimacy of relevant agencies and organizations as civil subjects to represent environmental public interests. Finally, it clearly stipulates the responsibility for ecological restoration, expands the way of undertaking tort liability caused by environmental damage, and solves the problem that it was limited to "restoration" in the past and could not be actually performed. | Counterfeit |
Text : Expression of miR-181a-5p associates with the proliferation and progression of cancer cells via its targets. This study was designed to investigate the effect of miR-181a-5p and its target inositol polyphosphate-5-phosphatase A (INPP5A) on the progression of cervical cancers. Upregulation of miR-181a-5p was revealed in the cervical cancer cell lines HeLa and SiHa in comparison with a normal cervical epithelium cell line End1/E6E7 (p < 0.001). The inhibition and upregulation of miR-181a-5p in cervical cancer cell lines significantly reduced or increased cell proliferation and invasion capacity, accompanied with enhanced or reduced apoptosis (p < 0.05). Moreover, INPP5A overexpression significantly inhibited cell proliferation and invasion capacity and enhanced cell apoptosis. The target relationship of miR-181a-5p to INPP5A was demonstrated by both the results of the Dual-Luciferase Reporter Assay and the fact that the miR-181a-5p mimic attenuated INPP5A's effect on cell proliferation, invasion, and apoptosis. To sum up, the overexpression of miR-181a-5p enhanced cell proliferation and invasion and inhibited apoptosis of cervical cancer cells by negatively targeting INPP5A. Therefore, inhibition of miR-181a-5p might benefit the inhibition of cervical cancer cell invasion. | Counterfeit |
Text : Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. The expression of novel tumor-associated kinases has the potential to dramatically shape tumor cell behavior. Identifying tumor-associated kinases can lend insight into patterns of tumor growth and characteristics. In the present study, we investigated the receptor tyrosine kinase-like orphan receptor 2 (Ror2), a new tumor-associated kinase, in RCC primary tumors and cell lines. Knockdown of Ror2 expression in RCC cells with specific shRNA significantly reduced cell proliferation and induced apoptosis. Using in vitro migration and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. In RCC, Ror2 expression correlated with expression of genes involved at the cell cycle and migration, including PCNA, CDK1, TWIST, and MMP-2. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a Ror2 shRNA plasmid significantly inhibited tumor growth. These findings suggest a novel pathway of tumor-promoting activity by Ror2 within renal carcinomas, with significant implications for unraveling the tumorigenesis of RCC. | Authentic |
Text : To explore the efficacy and safety of irreversible electroporation (IRE) ablation combined with natural killer (NK) cells in the treatment of locally advanced pancreatic cancer (LAPC). A total of 92 LAPC patients treated in our hospital from January 2016 to January 2017 were enrolled, and there were 46 cases of percutaneous IRE as IRE group, and 46 cases of IRE combined NK cell therapy as IRE-NK group. The clinical information of all the patients was collected, and the short-term efficacy, changes in the serum immunological indicators after treatment, carbohydrate antigen 19-9 (CA19-9) level, and incidence of adverse reactions were compared between the two groups of patients. Besides, the overall survival (OS) and disease-free survival (DFS) of patients were followed up and recorded. On 1 month after treatment, all the patients underwent efficacy assessment, which showed the overall response rate of patients in IRE-NK group was significantly superior to that in IRE group. One and 7 days after operation, the level of CA19-9 was obviously raised in the two groups, with a statistically significant difference, and it declined 30 days postoperatively. Seven and 30 days after operation IRE-NK group had a notably lower level of CA19-9 than IRE group. After treatment, all the patients exhibited considerably higher lymphocyte count and notably enhanced lymphocyte function, and all the indicators in IRE-NK group were higher than those in IRE group. Besides, the levels of serum interleukin (IL)-2, TNF-β and IFN-γ in IRE-NK group were remarkably higher than those in IRE group, whereas there were no statistically significant differences in the levels of IL-4, IL-6 and IL-10 between the two groups. All the patients were followed up for 6-29 months, and there were no statistically significant differences in the DFS and OS between IRE group and IRE-NK group. IRE ablation combined with NK cells has excellent efficacy in treating LAPC, and they can exert a synergistic treatment effect to enhance the immune function of patients and reduce CA19-9 expression, with tolerable adverse reactions. | Authentic |
Text : In this study, we explored the NPC-specific expression of ZFAS1 and the mechanism of ZFAS1-mediated growth, aggressiveness and tumorigenesis in NPC. The expression profile of lncRNAs was detected in NPC tissues and matching para-carcinoma tissues using microarray analysis. LncRNA-miRNA and miRNA-mRNA interaction networks were constructed using the miRcode v11 and TargetScanHuman v7.2 web server and then validated using dual-luciferase assay. Western blot and RT-qPCR were performed to detect protein and RNA expression. The effects of ZFAS1, miR-892b and LPAR1 dysregulation on the proliferative, migratory and invasive abilities of NPC cells were observed using colony formation, cell counting kit-8 (CCK-8) and transwell assays in vitro. In vivo, a xenograft nude mouse model was established to detect the impact of ZFAS1 dysregulation on the tumorigenicity of NPC cells. The expression of multiple lncRNAs, of which ZFAS1 was up-regulated, was dysregulated in NPC tissues. ZFAS1 directly targeted miR-892b, and miR-892b negatively regulated the expression of downstream LPAR1. The proliferation, migration and invasion of NPC cells could be largely enhanced by the downregulation of miR-892b as well as the up-regulation of ZFAS1 and LPAR1, while the overexpression of miR-892b and the downregulation of ZFAS1 and LPAR1 decreased these abilities. In nude mice, the growth of tumour xenografts formed by HONE1 cells was significantly suppressed when ZFAS1 was silenced. The study demonstrated that lncRNA ZFAS1 may act as a promoter of tumorigenesis and metastasis in nasopharyngeal carcinoma, by up-regulating the expression of LPAR1 in a miR-892b-dependent manner. | Authentic |
Text : Colon cancer (CC) is the third most common tumor worldwide. Colon carcinogenesis is strongly linked to inflammation. The initiation and progression of colon cancer may be influenced by epigenetic processes. Cancer metastasis is a multistep process involving several genes and their products. During tumor metastasis, cancer cells first enhance their proliferative capacity by lowering autophagy and apoptosis, and then, their capacity is stimulated by boosting tumors' ability to take nutrients from the outside via angiogenesis. Traditional treatment focuses on eliminating tumor cells by triggering cell death or activating the immune system, which often results in side effects or chemoresistance recurrence. On the contrary, Chinese medicine theory considers the patient's entire inner system and aids in tumor shrinkage while also taking into account the mouse' general health. Because many Chinese herbal medicines (CHM) are consumed as food, using edible CHMs as a diet resource therapy for colon cancer treatment is a viable option. Two traditional Chinese herbs, Astragalus membranaceus and Curcuma zedoaria, are commonly utilized jointly in colon cancer preventive therapy. As a result, the anticancer effect of astragalus and curcumin (AC) on colon cancer suppression in an 18-week AOM-DSS colon cancer mouse model is investigated in this research. These findings may offer a scientific foundation for investigating colon cancer diagnostic biomarkers and therapeutic application of AC in colon cancer treatment. These studies also highlighted the potential effect and mechanism of AC in the treatment of colon cancer, as well as providing insight into how to effectively use it. | Counterfeit |
Text : Cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors have been shown to significantly prolong the overall survival (OS) in a wide range of cancers. However, its application in clear cell renal cell carcinoma (ccRCC) is limited due to the therapy response, and the prognostic value of CTLA4 in ccRCC has not been investigated in detail. By using immunohistochemistry, Kaplan-Meier (K-M) analysis, uni- and multi-variate Cox analysis, we comprehensively and systematically studied the prognostic value of CTLA4 in ccRCC. Then, we applied Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and CIBERSORT, ESTIMATE algorithm, ssGSEA and somatic mutation analyses to reveal the impact of CTLA4 on the landscape of tumor-infiltrating lymphocytes (TILs) infiltration and genetic mutation. Besides, given current concerns caused by combined immunotherapy, we also investigated the relationship between CTLA4 and other immune checkpoints. In vitro experiment and data mining showed that, CTLA4 was up-regulated in ccRCC tissues and closely related to the disease progression as well as a poor prognosis. Deeper researches demonstrated that CTLA4 regulates T cell activation and was significantly linked to TIL-abundant tumor microenvironment (TME), but was accompanied by an immunosuppressed phenotype. Mutation analysis showed that CTLA4 was associated with more frequent BRCA-associated protein 1 (BAP1) mutation. Moreover, we found that CTLA4 was markedly correlated with multiple immune checkpoints, which suggested that ccRCC patients with high expressed CTLA4 may benefit more from immune checkpoint blockades (ICBs) combined therapy. CTLA4 has a profound impact on the landscape of TILs and genetic mutation, and can be used as the biomarker with high prognosis value in ccRCC. | Authentic |
Text : Pancreatic adenocarcinoma is thought to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs), which exhibit similar morphological and genetic features to pancreatic ductal adenocarcinoma (PDAC). Therefore, a better understanding of the biological features underlying the progression of PanIN is essential to development more effective therapeutic interventions for PDAC. In recent years, numerous studies have reported that MET proto-oncogene receptor tyrosine kinase (c-MET) is a potential marker of pancreatic cancer stem cells (CSCs). CSCs have been revealed to initiate and propagate tumors in vitro and in vivo, and are associated with a chemoresistant phenotype. However, in vivo models using a xenograft approach are limited. In the present study, the morphological phenotype, molecular alteration and biological behavior of neoplasia in Pdx-1Cre/+, KrasLSL-G12D/+ and Metflox/flox and wild-type mice was analyzed. The results demonstrated that while oncogenic KrasLSL-G12D/+ increased PanIN initiation and significantly decreased survival rate compared with wild-type mice, no additive effect of c-Met receptor signaling on PanIN progression or prognosis was observed. Following gemcitabine administration, c-Met inhibition in Kras LSL-G12D/+ mice significantly decreased the total surface area of PanIN lesions and the number of anti-proliferation marker protein Ki-67 positive cells occupying PanIN lesions compared with Met+/+ mice. In conclusion, complete inhibition of the c-Met signaling pathway with chemotherapy may be useful for the treatment of pancreatic cancer. | Authentic |
Text : The efficacy of tivantinib may have some potential in treating MET-high hepatocellular carcinoma, and we aim to compare tivantinib with placebo for the treatment of MET-high hepatocellular carcinoma. Several databases including PubMed, Cochrane Library, Web of Science, EBSCO, and EMbase have been systematically searched through March 2022, and we included studies regarding the treatment of MET-high hepatocellular carcinoma by using tivantinib versus placebo. We finally include three RCTs. In comparison with placebo for MET-high hepatocellular carcinoma, tivantinib reveals no significant influence on overall survival (P=0.21), progression-free survival (P=0.13), time to progression (P=0.38), or grade ≥3 anemia (P=0.50) but increases the incidence of grade ≥3 neutropenia (P=0.04). Tivantinib may provide no additional benefits for MET-high hepatocellular carcinoma. | Authentic |
Text : Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast-secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial-mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial-mesenchymal transition-related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects. | Authentic |
Text : Accounting for 25% of all the cancers and 20% of the cancer-related mortality, lung cancer is one of the devastating types of cancers. Due to an increase in the incidence of lung cancer and limited treatment options, there is a pressing need to look for novel drug options and to identify potential therapeutic targets. Long non-coding RNAs (LncRNAs) have been considered to be important therapeutic targets due to their plethora of cellular roles. Herein, we investigated the therapeutic potential of UCA1 in lung cancer and also attempted to examine the underlying mechanism through UCA1 exerts its growth inhibitory effects on cancer cells. The quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to perform the expression analysis. The CCK-8 assay was used to monitor the growth of the cells. The AO/EB assay was used to check apoptosis and flow cytometry was used for cell cycle distribution. The wound heal and transwell assays were used to monitor the cell migration and invasion. It was found that the lncRNA UCA was significantly (p < 0.05) upregulated in the lung cancer cells and silencing of UCA1 could inhibit the proliferation of the SK-MES-1 lung cancer cells via induction of G2/M cell cycle arrest and apoptosis. Moreover, UCA1 silencing could also suppress the migration and invasion of the SK-MES-1 cells. The LncRNA UCA1 was also found to upregulate the expression of miR-143, and overexpression of miR-143 could also suppress the proliferation, migration, and invasion of the SK-MES-1 lung cancer cells. Both UCA1 silencing and miR-143 overexpression could cause a significant decrease in the expression of mitogen-activated protein kinase 1 (MAPK1). Therefore, it is concluded that UCA1 regulates the growth of the SK-MES-1 lung cancer by inhibition of MAPK1 via miR-143 upregulation. UCA1, as well as miR-143, may be essential therapeutic targets for the management of lung cancer and warrant further investigations. | Authentic |
Text : The association between the Dietary Inflammatory Index (DII) and breast cancer risk has been widely reported in recent years, but there is still controversy about whether a pro-inflammatory diet is a risk factor for breast cancer. We conducted a meta-analysis to investigate the relationship between the DII and breast cancer risk in pre-menopausal and post-menopausal women. We comprehensively searched PubMed, Embase and the Cochrane Library in January 2021 to identify articles reporting an association between the DII and breast cancer risk. A pooled analysis was conducted with 14 studies covering 312,885 participants. Overall, women in the most pro-inflammatory diet category were at greater risk for breast cancer than those in the most anti-inflammatory category (relative risk [RR]=1.37, 95% confidence interval [CI] 1.17-1.60, P<0.001). This association was strong in both pre-menopausal women (RR=1.87, 95% CI 1.17-2.99, P=0.001) and post-menopausal women (RR=1.23, 95% CI 1.08-1.40, P<0.001). Thus, a strong and independent association was observed between a pro-inflammatory diet (assessed using the DII score) and breast cancer risk, irrespective of menopausal status. Further studies will be required to determine the relationship between a pro-inflammatory diet and different subtypes of breast cancer. | Authentic |
Text : In recent years, numerous studies have confirmed the role of chitosan nanoparticles (CS NPs) as a promising drug delivery carrier for improving the efficiency of anticancer drug in the treatment of cancer. However, the possible biological effects of CS NPs on tumour cells and underlying mechanisms are still unclear. Recently, reactive oxygen species (ROS)-mediated cell apoptosis has been implicated in the regulation of cell death. In this study, we found that CS NPs induced the massive generation of ROS and resulted in apoptosis of hepatocellular carcinoma cells (SMMC-7721) through activating the mitochondrial pathway and endoplasmic reticulum stress. These results suggest an important role of ROS in CS NPs-induced cancer cell death. | Authentic |
Text : The aim of this study was to investigate the role of NEAT1 in hepatocellular carcinoma (HCC), and probe whether NEAT1 participate in the epithelial-mesenchymal transition (EMT) and metastasis regulated by HIF-2α. Expression of lncRNA NEAT1 was initially assessed in HCC tissues and in a series of HCC cell lines. The correlations between NEAT1 levels and HIF-2α were analyzed through plasmid vector construction. The potential underlying mechanisms of NEAT1 in HCC were performed through in vitro and in vivo functional assays. Expression of NEAT1, HIF-2α were significantly increased in HCC tissues and cell lines. Then, in vitro assays revealed that NEAT1 promotes EMT and metastasis by stimulating the inactivation of HIF-2α in HCC. An in vivo animal model also demonstrated the cancer promotion mechanism of NEAT1. In this study, we found that the NEAT1 was high expression in HCC. NEAT1 promotes tumor cell EMT, migration and invasion capacities by stimulating the activation of HIF-2α in HCC. | Authentic |
Text : Angiogenesis plays an essential role in the growth and metastasis of a number of tumors. Anti-angiogenic drugs are able to normalize tumor vasculature and inhibit tumor growth. Therefore, it has been hypothesized that the combination of cytotoxic chemotherapy drugs and angiogenesis inhibitors may exert complementary therapeutic benefits in the treatment of cancer. In the present study, the effect of the angiogenesis inhibitor, recombinant human endostatin (Endostar), in combination with cisplatin, was evaluated in C57/BL/6 mouse xenografts under different administration sequences. The drug combinations and sequences of administration were analyzed within the cancer xenografts for any inhibitory effects. Changes in the cell cycle distribution of the cells were monitored using flow cytometry. The effects of Endostar, particularly a reduction in the density of microvessels, were assessed using a method that employed anti-cluster of differentiation 31 antibodies. The concentration of cisplatin in the blood and tumor tissue at various time-points following administration was detected by high-performance liquid chromatography. The tumor tissues that received simultaneous Endostar and cisplatin exhibited increased inhibition of tumor growth and improved cell cycle distribution compared with those that received cisplatin alone, or those in which Endostar was administered prior to cisplatin. The simultaneous administration of the drugs resulted in the lowest microvessel density in the xenografts. Under these conditions, the concentration of cisplatin was revealed to be the highest in the grafted tumor tissue. The results of the present study suggest that the co-administration of Endostar and cisplatin may aid in the optimization of the antitumor activity of cisplatin. | Authentic |
Text : Brown seaweeds contain bioactive compounds that show anti-tumorigenic effects. These characteristics have been repeatedly observed in the Lessoniaceae family. Egregia menziesii, a member of this family, is distributed in the North Pacific and its properties have been barely studied. We evaluated herein the cytotoxic and anti-proliferative activity of extracts of this seaweed, through toxicity assay in Artemia salina and lymphocytes, and MTT proliferation assay, in Bergmann glia cells, 3T3-L1 and brain cancer cell lines. E. menziesii's extracts inhibited the spread of all the tested cell lines. The hexane extract showed the highest cytotoxic activity, while the methanol extract was moderately cytotoxic. Interestingly, seaweed extracts displayed a selective inhibition pattern. These results suggest that E. menziesii's extracts might be good candidates for cancer prevention and the development of novel chemotherapies due to its highest cytotoxicity in transformed cells compare to glia primary cultures. | Authentic |
Text : To investigate the specific function of long noncoding RNA FGD5 antisense RNA 1 (lncRNA FGD5-AS1) in glioma. The level of FGD5-AS1 was detected in clinical samples and cell lines by qRT-PCR. Small interfering RNA (siRNA) of FGD5-AS1 or scramble siRNA was transfected into U87 cell lines to examine the role of FGD5-AS1 on glioma development. The proliferation of glioma cells was tested by Cell Counting Kit-8 (CCK-8), the migration and invasion of glioma cells were tested by transwell assay without matrigel or with matrigel. Western blot was used to detect the protein expression, and XAV-939 was used to inhibit wnt/β-catenin pathway. The effect of FGD5-AS1 on tumorigenesis of glioma was confirmed by xenograft nude mice model. FGD5-AS1 was significantly increased in glioma tissues and cells. Loss of FGD5-AS1 inhibited the proliferation, migration and invasion of U87 cells. Furthermore, overexpression of FGD5-AS1 increased the mRNA and protein levels of β-catenin and cyclin D1. Blocking of wnt/β-catenin using XAV-939 reversed the promotion role of FGD3-AS1 on glioma cells' migration and invasion. The in vivo tumor growth assay showed that FGD3-AS1 accelerated glioma tumorigenesis with activating wnt/β-catenin pathway. Our research emphasized FGD5-AS1 acting as an oncogene by regulating wnt/β-catenin signaling pathway, thus providing some novel experimental basis for clinical treatment of glioma. | 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 : The cancer stem cell (CSC) hypothesis was first proposed over 40 years ago. Advances in CSC isolation were first achieved in hematological malignancies, with the first CSC demonstrated in acute myeloid leukemia. However, using similar strategies and technologies, and taking advantage of available surface markers, CSCs have been more recently demonstrated in a growing range of epithelial and other solid organ malignancies, suggesting that the majority of malignancies are dependent on such a compartment.Primary liver cancer consists predominantly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It is believed that hepatic progenitor cells (HPCs) could be the origin of some HCCs and ICCs. Furthermore, stem cell activators such as Wnt/β-catenin, TGF-β, Notch and Hedgehog signaling pathways also expedite tumorigenesis, and these pathways could serve as molecular targets to assist in designing cancer prevention strategies. Recent studies indicate that additional factors such as EpCAM, Lin28 or miR-181 may also contribute to HCC progression by targeting HCC CSCs. Various therapeutic drugs that directly modulate CSCs have been examined in vivo and in vitro. However, CSCs clearly have a complex pathogenesis, with a considerable crosstalk and redundancy in signaling pathways, and hence targeting single molecules or pathways may have a limited benefit for treatment. Many of the key signaling molecules are shared by both CSCs and normal stem cells, which add further challenges for designing molecularly targeted strategies specific to CSCs but sparing normal stem cells to avoid side effects. In addition to the direct control of CSCs, many other factors that are needed for the maintenance of CSCs, such as angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance, should be taken into consideration when designing therapeutic strategies for HCC. Here we provide a brief review of molecular signaling in liver CSCs and present insights into new therapeutic strategies for targeting liver CSCs. | Authentic |
Text : Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Hispidulin (10, 20 μmol/L) decreased the viability of ccRCC cells in dose- and time-dependent manners without affecting that of normal tubular epithelial cells. Moreover, hispidulin treatment dose-dependently increased the levels of cleaved caspase-8 and caspase-9, but the inhibitors of caspase-8 and caspase-9 only partly abrogated hispidulin-induced apoptosis, suggesting that hispidulin triggered apoptosis via both extrinsic and intrinsic pathways. Moreover, hispidulin treatment significantly inhibited the activity of sphingosine kinase 1 (SphK1) and consequently promoted ceramide accumulation, thus leading to apoptosis of the cancer cells, whereas pretreatment with K6PC-5, an activator of SphK1, or overexpression of SphK1 significantly attenuated the anti-proliferative and pro-apoptotic effects of hispidulin. In addition, hispidulin treatment dose-dependently activated ROS/JNK signaling and led to cell apoptosis. We further demonstrated in Caki-2 xenograft nude mice that injection of hispidulin (20, 40 mg·kg-1·d-1, ip) dose-dependently suppressed tumor growth accompanied by decreased SphK1 activity and increased ceramide accumulation in tumor tissues. Our findings reveal a new explanation for the anti-tumor mechanisms of hispidulin, and suggest that SphK1 and ceramide may serve as potential therapeutic targets for the treatment of ccRCC. | Authentic |
Text : Although microRNAs have been validated to play prominent roles in the occurrence and development of human bladder cancer (BC), alterations and function of many microRNAs (miRNAs) in bladder cancer invasion are not fully explored yet. miR-146b was reported to be a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in bladder cancer remain unclear. Here we discovered that miR-146b was frequently upregulated in bladder cancer tissues compared with adjacent non-cancerous tissues. Inhibition of miR-146b resulted in a significant inhibitory effect on the invasion of bladder cancer cells by reducing mmp2 mRNA transcription and protein expression. We further demonstrated that knockdown of miR-146b attenuated ETS2 expression, which was the transcription factor of matrix metalloproteinase (MMP)2. Moreover, mechanistic studies revealed that miR-146b inhibition stabilized ARE/poly(U)-binding/degradation factor 1 (auf1) mRNA by directly binding to its mRNA 3' UTR, further reduced ets2 mRNA stability, and finally inhibited mmp2 transcription and attenuated bladder cancer invasion abilities. The identification of the miR-146b/AUF1/ETS2/MMP2 mechanism for promoting bladder cancer invasion provides significant insights into understanding the nature of bladder cancer metastasis. Targeting the pathway described here may be a novel approach for inhibiting invasion and metastasis of bladder cancer. | Authentic |
Text : Epithelial ovarian cancer (EOC) is one of the most common gynecological cancers and has the highest mortality rate thereof. We found abundant eukaryotic translation initiation factor 5A1 (EIF5A1) in 54 EOC tissues, and high EIF5A1 levels predicted poor survival. EIF5A1 ectopic expression enhanced EOC cell proliferative, migration, and invasive capabilities, while EIF5A1 knockdown suppressed them. Most importantly, GC7 (N1-guanyl-1,7-diaminoheptane, an EIF5A1 hypusination inhibitor) could reverse the effect of EIF5A1 upregulation on EOC cell proliferation, migration, and invasion and mutant type EIF5A1K50A plasmid [bearing a single point mutation (K50 → A50) that prevents hypusination] had no effects on these malignant behaviors. Our findings imply that EIF5A1 is a vital regulator of EOC proliferation and progression and is a potential prognostic marker and therapeutic target in EOC. | Authentic |
Text : Metastasis is an important factor in the poor prognosis of breast cancer. As an important core clock protein, brain and muscle arnt-like 1 (BMAL1) is closely related to tumorigenesis. However, the molecular mechanisms that mediate the role of BMAL1 in invasion and metastasis remain largely unknown. In this study, we investigated the BMAL1 may take a crucial effect in the progression of breast cancer cells. BMAL1 and MMP9 expression was measured in breast cell lines. Transwell and scratch wound-healing assays were used to detect the movement of cells and MTT assays and clonal formation assays were used to assess cells' proliferation. The effects of BMAL1 on the MMP9/NF-κB pathway were examined by western blotting, co-immunoprecipitation and mammalian two-hybrid. In our study, it showed that cell migration and invasion were significantly enhanced when overexpressed BMAL1. Functionally, overexpression BMAL1 significantly increased the mRNA and protein level of matrix metalloproteinase9 (MMP9) and improved the activity of MMP9. Moreover, BMAL1 activated the NF-κB signaling pathway by increasing the phosphorylation of IκB and promoted human MMP9 promoter activity by interacting with NF-kB p65, leading to increased expression of MMP9. When overexpressed BMAL1, CBP (CREB binding protein) was recruited to enhance the activity of p65 and further activate the NF-κB signaling pathway to regulate the expression of its downstream target genes, including MMP9, TNFα, uPA and IL8, and then promote the invasion and metastasis of breast cancer cells. This study confirmed a new mechanism by which BMAL1 up-regulated MMP9 expression to increase breast cancer metastasis, to provide research support for the prevention and treatment of breast cancer. | Authentic |
Text : Cutaneous squamous cell carcinoma (CSCC), an epidermal keratinocyte-derived skin tumor, is one of the most leading causes of cancer-associated morbidity and mortality worldwide. Long noncoding RNAs have emerged as key regulators of tumor development and progression. Recent studies have identified LINC00319, a long intergenic noncoding RNA, as an oncogene in lung cancer. However, the biological role of LINC00319 in CSCC remains largely unknown. The current study aimed to explore the role of LINC00319 in CSCC and uncover the molecular mechanisms. In current study, we found that LINC00319 was significantly upregulated in both CSCC tissues and cell lines. Besides, the χ2 test showed that increased expression of LINC00319 was associated with larger tumor size, advanced TNM stage, and lymphovascular invasion. Gain-of-function and loss-of-function approaches were applied to investigate the effects of LINC00319 on CSCC cells. Functional studies demonstrated that LINC00319 promoted CSCC cell proliferation, accelerated cell cycle progression, facilitated cell migration and invasion, and inhibited cell apoptosis. Mechanistic studies revealed that LINC00319 exerts its oncogenic functions in CSCC via miR-1207-5p-mediated regulation of cyclin-dependent kinase 3. Taken together, upregulation of LINC00319 implies a potential link with poor prognosis and reflects CSCC progression. Collectively, this study may provide some evidence for LINC00319 as a candidate target in CSCC treatment. | Authentic |
Text : Folate receptor-mediated staining solution detection (FRD) has been recently suggested as an effective tool in the cervical cancer screening. We aim to compare the accuracy of FRD to human papillomavirus (HPV) and thinprep cytology test (TCT) based on cytology-based biopsy.During May 2016 and December 2016, we recruited women who presented for routine cervical lesion screening. The eligible cases were nonpregnant women and not in the menstrual period, aging between 25 and 65. All eligible women were screened with TCT, HPV, FRD testing, and colposcopy.A total of 216 women include 137 (63.4%) cases of cervical inflammation, 27 (12.5%) cases of cervical intraepithelial neoplasia 1 (CIN 1), 51 (23.6%) cases of CIN 2, 34 (15.7%) cases of CIN 3, and 12 (5.6%) cases of cervical cancer. The sensitivity were 93.81%, 76.29%, 80.41% for HPV testing, TCT testing, and FRD testing, respectively. The specificities were 16.46%, 34.15%, and 68.29%, respectively. FRD has statistically significant higher specificity than HPV testing and TCT (both P < .05). However, no differences were found in sensitivity (both P > .05). The positive predictive value (PPV), negative predictive value (NPV), and Kappa consistency coefficient were 39.91%, 81.82%, and 0.08% for HPV testing, 40.66%, 70.89%, and 0.09% for TCT, and 60%, 85.5%, and 0.46% for FRD testing.FRD had favorable accuracy and efficacy in detecting cervical cancer, and therefore could be used as an effective screening tool for cervical cancer screening. | Authentic |
Text : Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors. | Authentic |
Text : Magnesium alloy is a potential biomedical implant because of its outstanding biodegradability and mechanical properties. But the poor corrosion resistance of AZ91 magnesium alloy in physiological solution limits its biomedical applications. In order to improve the corrosion resistance and biological performance of AZ91 magnesium alloy, we have fabricated a strontium-substituted porous hydroxyapatite (Sr-HAP)/zinc oxide (ZnO) duplex layer on AZ91 magnesium alloy by electrodeposition. The porous Sr-HAP/ZnO duplex-layer coating on AZ91 magnesium alloy was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, high-resolution scanning electron microscopy and energy dispersive X-ray analysis. Also, the mechanical properties of the duplex-layer coating were evaluated using adhesion and Vickers micro-hardness tests. The effects of the duplex-layer coating on the corrosion behavior of AZ91 magnesium alloy were also investigated in simulated body fluid using electrochemical studies. The potentiodynamic polarization and electrochemical impedance spectroscopy results indicated that the corrosion resistance of AZ91 magnesium alloy was significantly improved by the duplex-layer coating. The in vitro cell-material interaction of the duplex-layer coating was observed with human osteosarcoma MG63 cells for cell viability at 1, 4 and 7 days of incubation and the coating exhibited good biocompatibility. Hence, from the obtained results we believe that the duplex-layer made of ZnO together with porous Sr-HAP on AZ91 magnesium alloy could provide effective corrosion protection and enhanced bioactivity. Thus, duplex-layer-coated AZ91 magnesium alloy can serve as a promising candidate for orthopedic applications. | Counterfeit |
Text : The aim of this study was to investigate the effect of long noncoding RNA (lncRNA) urogenital carcinoma antigen 1 (UCA1) on drug resistance in A549/DDP cell and explore its underlying mechanism. The inhibition rate and IC 50 of DDP were detected in A549 and A549/DDP cells by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay. The expression of lncRNA UCA1 was measured in A549 and A549/DDP cells by quantitative real-time polymerase chain reaction. The expressions of N-cadherin, E-cadherin, vimentin, and Snail were detected in A549 and A549/DDP cells by Western blot analysis. Results showed that the IC 50 of DDP was 16.20 ± 2.27 μmol/L and 69.72 ± 4.83 μmol/L in A549 and A549/ DDP cells, respectively. Compared with the A549 group, the expressions of N-cadherin, vimentin, and Snail was significantly upregulated in A549/DDP group, but E-cadherin was significantly downregulated. Compared with the shCon group, the abundance of N-cadherin, vimentin, and Snail was significantly downregulated in short hairpin RNA UCA1 (shUCA1) group, while E-cadherin was significantly upregulated. Cell migration and invasion were significantly suppressed and IC 50 was reversed to 16.20 ± 2.27 μmol/L in the shUCA1 group. Silencing lncRNA UCA1 inhibited the migration and invasion of A549/DDP cells and reversed the resistance of A549/DDP cells to DDP. The mechanism might be related to downregulation of epithelial-mesenchymal transition, which will provide a new direction for the treatment of non-small-cell lung cancer with cisplatin. | Authentic |
Text : Pleomorphic lobular carcinoma in situ (PLCIS) has only recently been identified as a distinct pathological entity within classic lobular carcinoma in situ (CLCIS). As such, there is currently no consensus among clinicians regarding the optimal treatment of this disease. The present study determined the risk of concomitant invasive disease and ductal carcinoma in situ (DCIS) if PLCIS is observed on core needle biopsy (CNB) and collated the evidence regarding the risk of recurrence in relation to surgical margins and adjuvant therapy. In addition, the pertinent literature available through MedLine, PubMed, the WHO Clinical Trials Registry Platform and Google Scholar using appropriate keywords was reviewed. The pooled results of studies in the literature demonstrated a concomitant presence of invasive disease of 40%, and 15% for DCIS. The studies that examined recurrence rates indicated that the risk is reduced with ample resection margins (>2 mm) and adjuvant radiotherapy. However, recent studies raise concerns regarding breast conservation when pursuing clear margins. No level 1 evidence from prospective studies, randomized controlled trials (RCTs), or meta-analyses based on such RCTs was identified. This is a clinical issue that warrants investigation in appropriately powered well designed prospective studies for a satisfactory resolution of all concerns. | Authentic |
Text : We conducted this experimental study to estimate a risk of a high-risk group of low back pain (LBP) membership in workers who perform the manual material handling (MMH) tasks in an actual workplace setting. The subjects include healthy workers who were engaged in 12 MMH tasks at 6 manufacturing companies. We assessed the dynamic motion of trunk or lumbar spine using an industrial lumbar motion monitor (BioDynamics Laboratory of Ohio State University). The subjects were evaluated for the age, gender, years of working and anthropometric measurements (e.g., height, weight, shoulder height, elbow height, iliac height, leg length, trunk length, trunk circumference, iliac width, iliac depth, xiphoid width and xiphoid depth). Moreover, they were also evaluated for a risk of a high-risk group of LBP membership based on lift frequency, average twisting velocity, maximum moment, maximum sagittal flexion and maximum lateral velocity. The subjects who were engaged in a packaging at a detergent manufacturing company are at the greatest risk of LBP (63.76%). This was followed by packaging at a leather product manufacturing company (57.06%), packaging at a non-metallic casting material manufacturing company (57.03%), manual injection at a non-metallic casting material manufacturing company (52.00%), toggling at a leather product manufacturing company (46.09%), non-metallic casting material manufacturing company (42.88%), rolling at a non-metallic mineral product manufacturing company (42.12%), shooting at a non-metallic casting material manufacturing company (40.99%), vacuum processes at a leather product manufacturing company (35.00%), looping at a general industrial machinery manufacturing company (33.93%), setting at a leather product manufacturing company (30.22%) and packaging at a general metal product manufacturing company (22.02%). Our approach indicates that there is a risk of a high-risk group of LBP membership in workers who perform the MMH tasks. | Counterfeit |
Text : The present study aimed to investigate the effects of obatoclax (OBX) combined with gemcitabine (GEM) treatment on the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) related proteins of pancreatic cancer cell line BxPC‑3 under hypoxic conditions. Protein expression levels of hypoxia‑inducible factor 1α (HIF‑1α) in BxPC‑3 pancreatic cancer cells under normoxic and hypoxic conditions were detected by western blotting. Cells were divided into four groups: Normoxia group, hypoxia group, OBX group and OBX + GEM group. The proliferation activity of BxPC‑3 cells was detected by Cell Counting kit‑8. The migratory and invasive abilities of BxPC‑3 cells were detected by the scratch test and Matrigel assay, respectively. The protein expression levels of vimentin, E‑cadherin and p53 in BxPC‑3 cells were also detected by western blotting. HIF‑1α expression under hypoxic conditions was significantly increased compared with expression under normoxic conditions. Under hypoxic conditions, OBX treatment reduced cell activity, decreased cell migration and invasion, promoted the expression of E‑cadherin and p53. In the OBX + GEM group, BxPC‑3 cell activity decreased significantly, cell migration and invasion decreased significantly, the expression of vimentin was significantly reduced and the expression of E‑cadherin and p53 further increased. In conclusion, the present results demonstrated that under hypoxic conditions, OBX combined with a small dose of GEM may be able to inhibit the growth, migration and invasion of pancreatic cancer cells, possibly via inhibition of EMT process. These results may provide a promising strategy for pancreatic cancer therapy. | Authentic |
Text : Immunotherapy is a relatively new treatment regimen for cancer, and it is based on the modulation of the immune system to battle cancer. Immunotherapies can be classified as either molecular or cell-based immunotherapies, and both types have demonstrated promising results in a growing number of cancers. Indeed, several immunotherapies representing both classes are already approved for clinical use in oncology. While spectacular treatment successes have been reported, particularly for so-called immune checkpoint inhibitors and certain cell-based immunotherapies, they have also been accompanied by a variety of severe, sometimes life-threatening side effects. Furthermore, not all patients respond to immunotherapy. Hence, there is the need for more research to render these promising therapeutics more efficacious, more widely applicable, and safer to use. Whole-body in vivo imaging technologies that can interrogate cancers and/or immunotherapies are highly beneficial tools for immunotherapy development and translation to the clinic. In this review, we explain how in vivo imaging can aid the development of molecular and cell-based anti-cancer immunotherapies. We describe the principles of imaging host T-cells and adoptively transferred therapeutic T-cells as well as the value of traceable cancer cell models in immunotherapy development. Our emphasis is on in vivo cell tracking methodology, including important aspects and caveats specific to immunotherapies. We discuss a variety of associated experimental design aspects including parameters such as cell type, observation times/intervals, and detection sensitivity. The focus is on non-invasive 3D cell tracking on the whole-body level including aspects relevant for both preclinical experimentation and clinical translatability of the underlying methodologies. | Authentic |
Text : Urothelial carcinoma associated 1α (UCA1α) is a novel long non-coding RNA (lncRNA) that regulates bladder cancer proliferation, migration, and invasion. The target genes of UCA1α have, however, not been identified. To address this, a pCDNA3.1(+)-UCA1α over-expression vector was transfected into UM-UC-2 bladder cancer cells. Genes differentially expressed between pCDNA3.1(+)-UCA1α and pCDNA3.1(+) transfected cell were then detected by microarray and bioinformatics analysis. A total of 71 differentially expressed genes were identified, including 52 up-regulated genes and 19 down-regulated genes. As expected, the lncRNA UCA1α expression level was significantly increased when compared to that of pCDNA3.1(+) transfected cells. The five most significantly up-regulated and five most significantly down-regulated genes were selected, and their expression levels were also assessed by real time quantitative polymerase chain reaction and Western blot. The mRNA and protein expression levels of FOXI3 and GSTA3 were found to be significantly increased, and those of MED18 and TEX101 were found to be significantly decreased. Gene ontology (GO) clustering identified several significant biological processes, cellular components, and molecular functions, associated with lncRNA UCA1α over-expression. The differentially expressed genes were involved in several significant pathways as shown by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway clustering. Cell proliferation activity was significantly increased following overexpression of lncRNA UCA1α increasing over culture time. The present study identifies, for the first time, potential target genes for lncRNA UCA1α in bladder cancer, and provides a significant reference for studying the role of lncRNA UCA1α in bladder cancer. | Authentic |
Text : Similarities and differences in the cell cycle components, apoptosis and cytoskeleton-related molecules among mouse skin fibroblast cells (MSFs), mouse squamous cell lung carcinomas (SqCLCs) and mouse embryonic stem cells (mESCs) are important determinants of the behaviour and differentiation capacity of these cells. To reveal apoptotic pathways and to examine the distribution and the role of cell cycle-cell skeleton comparatively would necessitate tumour biology and stem cell biology to be assessed together in terms of oncogenesis and embryogenesis. The primary objectives of this study are to investigate the effects of flavopiridol, a cell cycle inhibitor, and geldanamycin, a heat shock protein inhibitor on mouse somatic, tumour and embryonic stem cells, by specifically focusing on alterations in cytoskeletal proteins, cell polarity and motility as well as cell cycle regulators. To meet these objectives, expression of several genes, cell cycle analysis and immunofluorescence staining of intracellular cytoskeletal molecules were performed in untreated and flavopiridol- or geldanamycin-treated cell lines. Cytotoxicity assays showed that SqCLCs are more sensitive to flavopiridol than MSFs and mESCs. Keratin-9 and keratin-2 expressions increased dramatically whereas cell cycle regulatory genes decreased significantly in the flavopiridol-treated MSFs. Flavopiridol-treated SqCLCs displayed a slight increase in several cell cytoskeleton regulatory genes as well as cell cycle regulatory genes. However, gene expression profiles of mESCs were not affected after flavopiridol treatment except the Cdc2a. Cytotoxic concentrations of geldanamycin were close to each other for all cell lines. Cdkn1a was the most increased gene in the geldanamycin-treated MSFs. However, expression levels of cell cytoskeleton-associated genes were increased dramatically in the geldanamycin-treated SqCLCs. Our results revealing differences in molecular mechanisms between embryogenesis and carcinogenesis may prove crucial in developing novel therapeutics that specifically target cancer cells. | Authentic |
Text : Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in the world. The gene glypican-3 (GPC3) is reported to be a potential therapeutic target for HCC. In this study, we use RNA interference with lentiviral vectors to explore the effect of GPC3 silencing on the biological behavior of HCC cells and the potential role of the GPC3 protein in the activation of epithelial-mesenchymal transition (EMT), which relates to HCC cell invasion and migration. Our data suggest that GPC3 silencing leads to a decrease in HCC cell proliferation and to an increase in apoptosis. We demonstrated that GPC3 silencing regulates cell invasion and migration, most probably through the activation of the EMT cellular program. In conclusion, GPC3 is associated with the HCC cell biological behavior, while the relationship between GPC3 and EMT in tumorigenesis of HCC deserves future investigation. | Authentic |
Text : Nuclear factor erythroid-derived-2-like 2(NRF2) regulates its downstream genes through binding with antioxidant responsive elements in their promoter regions. Hyperactivation of NRF2 results in oncogenesis and drug resistance in various cancers including non-small cell lung cancer (NSCLC). However, identification of the genes and pathways regulated by NRF2 in NSCLC warrants further investigation. We investigated the global NRF2 genomic binding sites using the high-throughput ChIP-Seq technique in KEAP1 (Kelch-like ECH-associated protein 1)-mutated A549 (NSCLC) cells. We next carried out an integrated analysis of the ChIP-Seq data with transcriptomic data from A549 cells with NRF2-knockdown and RNA-Seq data from TCGA patients with altered KEAP1 to identify downstream and clinically-correlated genes respectively. Furthermore, we applied transcription factor enrichment analysis, generated a protein-protein interaction network, and used kinase enrichment analysis. Moreover, functional annotation of NRF2 binding sites using DAVID v7 identified the genes involved in focal adhesion. Putative focal adhesion genes regulated by NRF2 were validated using qRT-PCR. Further, we selected one novel conserved focal adhesion gene regulated by NRF2-LAMC1 (laminin subunit gamma 1) and validated it using a reporter assay. Overall, the identification of NRF2 target genes paves the way for identifying the molecular mechanism of NRF2 signaling in NSCLC development and therapy. Moreover, our data highlight the complexity of the pathways regulated by NRF2 in lung tumorigenesis. | Authentic |
Text : Besides physical complications, COVID-19 is associated with psychological issues such as fear and anxiety. High resilience in nurses enables them to adopt positive coping mechanisms and successfully operate in the stressful environment of COVID-19 wards. The present study aimed to evaluate the correlation between COVID-19 fear and anxiety with resilience in the emergency nurses of the hospital affiliated with Kurdistan University of Medical Sciences (west of Iran) in 2021. This cross-sectional study was conducted on 295 emergency nurses of selected hospitals in Kurdistan province, Iran, in 2021. Data were collected using a demographic questionnaire, Fear of COVID-19 Scale (FCV-19S), Corona Disease Anxiety Scale (CDAS), and Connor-Davidson Resilience Scale (CD-RISC). Data analysis was performed in R software version 3.6.3. The mean scores of resilience, COVID-19 fear, and COVID-19 anxiety were 55.07 ± 19.82 (ranging from 0 to 100), 20 ± 7.37 (ranging from 7 to 35) and 36.48 ± 13.21 (ranging from 18 to 54) respectively. There was a negative and significant correlation between resilience with COVID-19 fear (r = -0.449, p = 0.001), COVID-19 anxiety (r = 0.458, p = 0.001). A significant correlation was observed between COVID-19 fear and anxiety, which indicated that if the other demographic variables remained unchanged, a one-unit increase in COVID-19 fear and anxiety decreased the mean resilience score by -0.66 (P = 0.008) and -0.34 (P = 0.015), respectively. COVID-19 fear and anxiety were significantly correlated. Therefore, providing training courses for promoting resilience could reduce the fear and anxiety of nurses during the COVID-19 pandemic. | Counterfeit |
Text : Accurate lung tumor identification is crucial for radiation treatment planning. Due to the low contrast of the lung tumor in computed tomography (CT) images, segmentation of the tumor in CT images is challenging. This paper effectively integrates the U-Net with the channel attention module (CAM) to segment the malignant lung area from the surrounding chest region. The SegChaNet method encodes CT slices of the input lung into feature maps utilizing the trail of encoders. Finally, we explicitly developed a multiscale, dense-feature extraction module to extract multiscale features from the collection of encoded feature maps. We have identified the segmentation map of the lungs by employing the decoders and compared SegChaNet with the state-of-the-art. The model has learned the dense-feature extraction in lung abnormalities, while iterative downsampling followed by iterative upsampling causes the network to remain invariant to the size of the dense abnormality. Experimental results show that the proposed method is accurate and efficient and directly provides explicit lung regions in complex circumstances without postprocessing. | Authentic |
Text : Cellular microbiology, which is the interaction between harmful microbes and infected cells, is important in the determination of the bacterial infection processes and in the progression of data of different cellular mechanisms. The therapeutic role of bacteria has gained attention since the known methods such as radiation, chemotherapy, and immunotherapy have got drawbacks. Bacteria have demonstrated a favorable impact in treating cancer through eradication of tumors. Bacteria, in cancer treatment, have proven to be promising and have been shown in some of the previous work that it can successfully suppress the growth of tumors. In this paper, we analyzed the difficulties and settlement for using bacteria in cancer therapy as well the mechanisms in which bacteria works in order to achieve tumor eradication. Future works may focus on the use of bacteria along with other treatments in order to achieve effective tumor therapy. | Authentic |
Text : A multitude of clinical studies showed the elevation of YKL-40 in subjects with different kinds of tumors. It is predicted that an inherent correlation exists between survivals of cancer patients with total YKL-40 serum levels, making this factor as a potential novel biomarker. However, the crucial role of YKL-40 in the dynamics of cancers, especially angiogenesis, has not yet been completely addressed. In this review, we highlighted the various facets of YKL-40 and its importance in cancer biology as a bio-shuttle in gene therapy. | Authentic |
Text : Synovial inflammation plays a major role in the pathogenesis of osteoarthritis (OA). This study investigated the effect of andrographolide (Andro) on synovial inflammation mediated by tumor necrosis factor-alpha receptor 2 (TNFR2) trafficking and its utility in attenuating OA progression. Knee joints were harvested from rats subjected to radial transection of the medial collateral ligament (MCLT) and medial meniscus (MMT) to examine the effect of Andro on synovial inflammation and OA progression. Quantitative real-time polymerase chain reaction was used to evaluate the expression of inflammatory factors in primary fibroblast-like synoviocytes (FLSs) after Andro treatment in vitro. The mechanism underlying Andro-mediated regulation of TNFR2 distribution and nuclear factor-κB (NF-κB) expression was verified using endosome maturation inhibitor hydroxychloroquine (HCQ) through flow cytometry, immunofluorescence, and western blot analysis. Andro treatment was found to reduce synovial inflammation and OA progression in vivo. Furthermore, a decrease in pain hypersensitivity and dorsal horn neuron activation was observed after treatment. Andro also downregulated the expression of inflammatory mediators and TNFR2 in FLSs. TNFR2 is crucial for the activation of the NF-κB signaling pathway, and Andro-induced degradation of TNFR2 was associated with lysosomal function, which in turn, reduced the downstream phosphorylation of p65 in the NF-κB signaling pathway. Andro could suppress synovial inflammation via regulation of TNFR2 trafficking and degradation. This also suggests it could be a potential treatment for the prevention of synovial inflammation and OA progression. This study provides strong evidence that Andro reduces NF-κB activation and inflammatory responses in OA FLSs via regulation of TNFR2 trafficking. The inhibition of TNFR2 and Andro could be a novel therapeutic approach for OA and pain management. | Authentic |
Text : TFF2 is a small, secreted protein with anti-inflammatory properties. We previously have shown that TFF2 gene delivery via adenovirus (Ad-Tff2) suppresses colon tumor growth in colitis associated cancer. Therefore, systemic administration of TFF2 peptide could potentially provide a similar benefit. Because TFF2 shows a poor pharmacokinetic, we sought to modify the TFF2 peptide in a manner that would lower its clearance rate but retain bioactivity. Given the absence of a sequence-based prediction of TFF2 functionality, we chose to genetically fuse the C-terminus of TFF2 with the carboxyl-terminal peptide of human chorionic gonadotropin β subunit, and inserted into adenoviral vector that expresses Flag. The resulting Ad-Tff2-CTP-Flag construct translates into a TFF2 fused with two CTP and three Flag motifs. Administered Ad-Tff2-CTP-Flag decreased tumorigenesis and suppressed the expansion of myeloid cells in vivo. The fusion peptide TFF2-CTP-Flag delivered by adenovirus Ad-Tff2-CTP-Flag as well purified recombinant fusion TFF2-CTP-Flag was retained in the blood longer compared with wild-type TFF2 delivered by Ad-Tff2 or recombinant TFF2. Consistently, purified recombinant fusion TFF2-CTP-Flag suppressed expansion of myeloid cells by down-regulating cyclin D1 mRNA in vitro. Here, we demonstrate for the very first time the retained bioactivity and possible pharmacokinetic advantages of TFF2 with a modified C-terminus. | Authentic |
Text : Brucea javanica, Azadirachta indica, and Typhonium flagelliforme are medicinal plants commonly used to treat conditions associated with tumour formation. This study aimed to determine the antiproliferative activity of these plants extracts on KB and ORL-48 oral cancer cell lines and to suggest their mode of cell death. The concentration producing 50% cell inhibition (IC50) was determined and the activity was examined under an inverted microscope. Immunohistochemistry fluorescent staining method (TUNEL) was performed to indicate the mechanism of cell death and the fragmented DNA band pattern produced was obtained for verification. Compared to Azadirachta sp. and Typhonium sp., the antiproliferative activity of Brucea sp. extract was the most potent on both KB and ORL-48 cells with IC50 of 24.37 ± 1.75 and 6.67 ± 1.15 µg/mL, respectively. Signs of cell attrition were observed 24 hr after treatment. Green fluorescent spots indicating cell death by apoptosis were observed in images of both cells following treatment with all the three extracts. DNA fragments harvested from Brucea-treated cells produced bands in a ladder pattern suggesting the apoptotic effect of the extract. It is thus concluded that Brucea sp. extract exhibited cytotoxic activity on ORL-48 cells and their action mechanism is via apoptosis. | Authentic |
Text : The application, development, and care of radical surgery combined with laparoscopic inguinal lymph node dissection for vulvar cancer. We searched the PubMed, Web of Science, the Cochrane Library, and EMBASE databases for published literature on the care of radical surgery combined with laparoscopic inguinal lymph node dissection for vulvar cancer up to June 2022. We used the following search terms and terms: "vulvar cancer," "injury," "radical vulvar cancer surgery," "laparoscopic inguinal lymph node dissection," and "care." Laparoscopic inguinal lymph node dissection has become a new surgical method for the treatment of vulvar cancer, and it effectively avoids all the problems associated with traditional surgery. In addition, radical vulvar cancer surgery and laparoscopic inguinal lymph node dissection combined with high-quality nursing interventions can promote patients' recovery and reduce the occurrence of complications, which has important clinical significance. This article reviews the application, development, and nursing care of radical vulvar cancer surgery combined with laparoscopic inguinal lymph node dissection. | Authentic |
Text : The objective of the study was to evaluate whether any association exists between systemic inflammation score (SIS) and adverse events (AEs) and survival of locally advanced rectal cancer patients treated with total mesorectal excision (TME) followed by adjuvant chemoradiotherapy. All of the 109 rectal cancer patients recruited between May 2008 and June 2015 were treated with TME followed by adjuvant chemoradiotherapy. The prognostic ability of SIS for overall survival (OS) was calculated by the receiver operating characteristic (ROC) curves. According to the classification of the SIS, 22 (20.2%), 59 (54.1%) and 28 (25.7%) patients were classified as a score of 2, 1 and 0, respectively. With an area under the curve (AUC) of 0.616, the SIS score of 1 was defined as the optimal cut-off value. Therefore, we divided the patients into the SIS-low group (SIS score of 1 or 0, n=87) and SIS-high group (SIS score of 2, n=22). Multivariate analysis indicated that SIS was associated with OS (HR 0.390, 95% CI 0.186-0.817, P=0.012). The 5-year OS rate in patients without adjuvant chemotherapy was lower than the patients with adjuvant chemotherapy (53.3% vs 75.8%, P=0.010). Multivariate analysis showed that adjuvant chemotherapy was associated with OS (HR 0.217, 95% CI 0.089-0.529, P=0.001). A marginal statistically significant difference was observed in terms of leukopenia during adjuvant chemoradiotherapy between the SIS-low group and the SIS-high group (P=0.05). These results suggest that SIS might serve as an independent biomarker for predicting AEs and prognosis in locally advanced rectal cancer treated with TME followed by adjuvant chemoradiotherapy. Strengthening treatment may be administered to locally advanced rectal cancer with high SIS score obtained before adjuvant chemoradiotherapy. | Authentic |
Text : In order to solve the great difficulties in cancer prevention, diagnosis, and treatment, a preparation method of iridium oxide nanocomposites under the microscope was proposed in this paper. Through a retrospective analysis of an experiment, IrOx nanoparticles were prepared by direct hydrothermal hydrolysis and loaded with chemotherapy drug adriamycin to construct nanodrug-loaded complex IrOx@DOX. At the same time, IrOx, as a sound-sensitive agent, can produce ROS under US irradiation, amplify intracellular oxidative stress, accelerate tumor cell death, and finally achieve the effect of SDT chemotherapy synergistic therapy. The experimental results show that IrOx@DOX has the dual response of pH and US, and the inhibition rates are 27%, 57%, and 76%, respectively. At the same time, ultrasound not only can enhance the uptake of nanoparticles by cells but also can promote the release of DOX in cells, which provides a basis for subsequent SDT chemotherapy synergistic therapy. Conclusion. Iridium oxide nanocomposite DOX combined with SDT can obtain a good therapeutic effect, which has positive feedback on the efficacy of chemotherapy and the therapeutic effect of cancer surgery. | Authentic |
Text : An increasing number of reports have shown that microRNAs (miRNAs) play a vital role in the occurrence and development of cancer by acting as tumor inhibitors or oncogenes. The purpose of this research was to explore whether the expression level of microRNA-15a-5p (miR-15a-5p) was related to TP53 regulated inhibitor of apoptosis 1 (TP53INP1) in cervical cancer, and to explore the role of miR-15a-5p in cervical cancer in vitro. Human cervical cancer tissues and adjacent normal tissues were obtained from 30 cervical cancer patients. Firstly, we carried out the quantitative Real Time-PCR (qRT-PCR) assay to evaluate the level of miR-15a-5p in cervical cancer tissues and cell lines. The TargetScan and the Dual-Luciferase Reporter Assay were used to confirm the relationship between TP53INP1 and miR-15a-5p. Besides, the Cell Counting Kit-8 (CCK-8) and the flow cytometry analysis were performed to detect the effect of miR-15a-5p on cell proliferation and apoptosis in cervical cancer cells. Our results showed that the expression of miR-15a-5p was enhanced in cervical cancer tissues and cells lines. The data from the Dual-Luciferase Reporter Assay demonstrated that TP53INP1 was a direct target of miR-15a-5p. We also found that TP53INP1 was down-regulated in the cervical cancer tissues and cell lines compared with the adjacent normal tissues and normal cervical cells. Besides, the down-regulation of miR-15a-5p depressed cervical cancer cell proliferation and enhanced cell apoptosis. Our results clearly suggested that the down-regulation of TP53INP1 successfully impaired the tumor-inhibition effects of miR-15a-5p inhibitor in cervical cancer cells. Our findings indicated that miR-15a-5p functioned as a tumor-promoting gene in cervical cancer by directly targeting TP53INP1, indicating that miR-15a-5p might be a potential treatment target for cervical cancer patients. | Authentic |
Text : Ovarian cancer (OC) is one of the most common gynecological malignancies. MicroRNAs (miRs) play a crucial role in the development and progression of OC, but the underlying mechanism remains largely unclear. Our study investigated the regulatory role of miR-148a in OC cell proliferation and invasion. We found that miR-148a was significantly downregulated in OC tissues compared to their matched adjacent nontumor tissues. In addition, its expression was also reduced in OC cell lines (SKOV3, ES-2, OVCAR, and A2780) compared to normal ovarian epithelial cells. Overexpression of miR-148a caused a significant decrease in OC cell proliferation and invasion, as well as reduced MMP9 protein levels. Transforming growth factor-β-induced 2 (TGFI2) was further identified as a target gene of miR-148a, and its protein expression was downregulated in OC cells after miR-148a overexpression. Restoration of TGFI2 attenuated the suppressive effects of miR-148a on OC cell proliferation and invasion. Moreover, we found that TGFI2 was remarkably upregulated in OC tissues when compared with their matched adjacent nontumor tissues, and observed a reverse correlation between miR-148a and TGFI2 expression in OC tissues. On the basis of these findings, we suggest that miR-148a inhibits OC cell proliferation and invasion partly through inhibition of TGFI2. Therefore, our study highlights the importance of the miR-148a/TGFI2 axis in the malignant progression of OC. | Authentic |
Text : High mobility group box 3 (HMGB3) is strongly involved in oncogenesis in a variety of cancers. In the present study, we have explored the role of HMGB3 in glioblastoma multiforme (GBM) tumorigenesis and have identified the microRNAs (miRNAs) miR-200b-3p and miR-200c-3p as negative regulators of HMGB3 expression. We began by determining that endogenous HMGB3 expression levels were significantly elevated in GBM tissues and in 3 GBM cell lines. To study the function of HMGB3 in GBM, we transfected a small-interfering RNA (siRNA) against HMGB3 into GBM cell lines U251 and LN229. MTT and tumour sphere assays demonstrated that HMGB3 knockdown significantly inhibited cell proliferation. Wound healing and transwell assays determined that HMGB3 knockdown substantially suppressed GBM cell migration and invasion. We evaluated the effects of HMGB3 knockdown on MAPK phosphorylation and target gene expression, finding that HMGB3 knockdown significantly reduced MAPK phosphorylation (p-ERK (1/2), p-p38, and p-JNK). We then used the biologic prediction algorithm TargetScan to identify the 3' untranslated region (3'-UTR) of HMGB3 as a target of miR-200b-3p and miR-200c-3p. Luciferase, qRT-PCR, and western blot assays confirmed that miR-200b-3p and miR-200c-3p bind and inhibit HMGB3 expression. Finally, Pearson correlation analyses demonstrated a negative correlation between relative HMGB3 mRNA and miR-200b/c-3p expression levels in GBM tissue samples. Overall, the present study strongly suggests that HMGB3 promotes GBM oncogenesis through the MAPK signalling pathway while miR-200b-3p and miR-200c-3p inhibit its expression. | Authentic |
Text : Oral cancer is one of the common oral cavity and pharynx cancers and its treatment is limited by early metastasis, late diagnosis and emergence of drug resistance. Herein we investigated the anticancer effects of Withaferin-A against the cisplatin-resistant SCC-4 human oral cancer cells. The proliferation rate of the human oral cancer cells was evaluated by CCK-8 assay. Apoptotic cell death was studied by acridine orange (AO) / ethidium bromide (EB) staining as well as by flow cytometry using annexin V/propidium iodide (PI) staining. Cell cycle analysis was performed by flow cytometry. Reactive oxygen species (ROS) examination was carried out by flow cytometry. Protein expressions were determined by immunoblotting. The results of the MTT assay showed that Withaferin-A caused decrease in the proliferation of SCC-4 cells and exhibited an IC50 of 14 µM. The anticancer effects of Withaferin-A were mainly due to the induction of apoptosis which was linked with upsurge of Bax and depletion of BCl-2. Annexin V/PI assay showed that the apoptotic cells were 0.75, 5.8, 12.4 and 22.66% at 0,7,14 and 28 µM concentrations of Withaferin-A. Withaferin-A also caused increase in the ROS and decrease in the MMP levels of the SCC-4 cells. Western blot analysis showed that the expression of LC3B II increased while of p62 decreased remarkably upon treatment with Withaferin-A, suggestive of autophagic cell death. Cell cycle analysis by flow cytometry showed that Withaferin-A caused increase in the G2/M phase cells triggering arrest of cancer cells at the G2/M checkpoint of the cell cycle. Finally, western blot analysis showed that Withaferin-A blocked the MAPK/RAS/RAF signalling pathway in the SCC-4 cells. These results suggest that Withaferin-A may prove a potent lead molecule in oral cancer treatment and warrants further investigations. | Counterfeit |
Text : Several studies have shown that anti-diabetic medications may modify the risk of cancer. We performed a systematic review and meta-analysis to evaluate the effect of alpha-glucosidase inhibitors (AGIs) on the risk of cancer in patients with diabetes mellitus. We conducted a systematic search of Medline, EMBASE, and Web of Science databases, up to September 30, 2016. Random-effects model was used to estimate the summary odds ratios (ORs) with 95% CI. Twenty-five studies (14 cohort, 7 case-control, and 4 randomized controlled trials) involving 1,285,433 patients with diabetes were included. Meta-analysis of observational studies showed that the use of AGIs was associated with a lower risk of developing cancer (OR = 0.86, 95% CI 0.78-0.96), especially gastrointestinal cancer (OR = 0.83, 95% CI 0.71-0.97). There was considerable heterogeneity across the studies introduced partly by the quality of included studies and adjustment for potential confounders. Meta-analysis of randomized controlled trials did not reveal any significant association between AGIs and cancer risk. Meta-analysis of observational studies indicated that AGIs may decrease the risk of cancer in individuals with diabetes. | Authentic |
Text : A characteristic feature of cancer cells is the activation of de novo fatty acid synthesis. Acetyl‑CoA carboxylase (ACC) is a key enzyme in fatty acid synthesis, accelerating the reaction that carboxylates cytosolic acetyl‑CoA to form malonyl‑CoA. ACC is highly expressed in several types of human cancer and is important in breast and prostate cancer cell growth. The aim of the present study was to investigate the effects of 5‑tetradecyloxy‑2‑furoic acid (TOFA), an allosteric inhibitor of ACC, on the proliferation and cell cycle progression of the ovarian cancer cell lines COC1 and COC1/DDP. TOFA was found to be cytotoxic to COC1 and COC1/DDP cells with a 50% inhibitory concentration (IC50) of ~26.1 and 11.6 µg/ml, respectively. TOFA inhibited the proliferation of the cancer cells examined in a time‑ and dose‑dependent manner, arrested the cells in the G0/G1 cell cycle phase and induced apoptosis. The expression of the cell cycle regulating proteins cyclin D1 and cyclin-dependent kinase (CDK) 4, as well as the expression of the apoptosis‑related proteins caspase‑3 and Bcl‑2, were detected by western blot analysis. Cyclin D1, CDK4 and Bcl‑2 protein expression was inhibited by TOFA, while caspase‑3 was cleaved and activated. To the best of our knowledge, the present study demonstrated for the first time that TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy. | Authentic |
Text : Recent studies have revealed that microRNAs (miRNAs) play a crucial role in the progression of tumorigenesis. Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. The aim of this study was to identify the exact role of hsa-miR-337 in the progression of NSCLC and to investigate the possible underlying mechanism. Hsa-miR-337 expression in NSCLC cells and 60 paired tissue samples were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the functions of hsa-miR-337 in vitro were identified by transwell assay and wound healing assay, respectively. Furthermore, the underlying mechanism was explored by RT-qPCR, Western blot assay, and luciferase assay. The expression level of hsa-miR-337 in NSCLC tissues was remarkably down-regulated when compared with that of adjacent normal samples. Moreover, the invasion and migration of NSCLC cells were significantly inhibited after overexpression of hsa-miR-337 in vitro. Moreover, after overexpression of hsa-miR-337 in vitro, the mRNA and protein levels of TCF7 were significantly down-regulated. Besides, the expression of TCF7 in NSCLC tissues was negatively correlated with the expression of hsa-miR-337. The above results suggested that hsa-miR-337 could repress the migration and invasion of NSCLC cells through directly targeting TCF7. Furthermore, hsa-miR-337 might offer a new therapeutic intervention for NSCLC patients. | Counterfeit |
Text : Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular feature of the tumor microenvironment. Mesothelial cells also participate in this complex and dynamic process. However, the molecular mechanisms underlying the hypoxia-driven mesothelial-tumor interactions that promote peritoneal metastasis of GC remain unclear. We determined the hypoxic microenvironment in PM of nude mice by immunohistochemical analysis and screened VEGFA by human growth factor array kit. The crosstalk mediated by VEGFA between peritoneal mesothelial cells (PMCs) and GC cells was determined in GC cells incubated with conditioned medium prepared from hypoxia-treated PMCs. The association between VEGFR1 and integrin α5 and fibronectin in GC cells was enriched using Gene Set Enrichment Analysis and KEGG pathway enrichment analysis. In vitro and xenograft mouse models were used to evaluate the impact of VEGFA/VEGFR1 on gastric cancer peritoneal metastasis. Confocal microscopy and immunoprecipitation were performed to determine the effect of hypoxia-induced autophagy. Here we report that in the PMCs of the hypoxic microenvironment, SIRT1 is degraded via the autophagic lysosomal pathway, leading to increased acetylation of HIF-1α and secretion of VEGFA. Under hypoxic conditions, VEGFA derived from PMCs acts on VEGFR1 of GC cells, resulting in p-ERK/p-JNK pathway activation, increased integrin α5 and fibronectin expression, and promotion of PM. Our findings have elucidated the mechanisms by which PMCs promote PM in GC in hypoxic environments. This study also provides a theoretical basis for considering autophagic pathways or VEGFA as potential therapeutic targets to treat PM in GC. | Authentic |
Text : Epithelial to mesenchymal transition (EMT) plays a critical role in drug resistance. The aim of the present study was to further elucidate its role by examining the effect of tissue transglutaminase (TG2) on EMT and drug resistance in breast cancer. An antisense lentiviral (LV) short hairpin (sh)RNA construct specific to the TG2 gene (TGM2) was designed, synthesized and stably transfected into MDA-MB-231 cells to silence TGM2 by RNA interference (RNAi). The transfected cells expressed low levels of TG2 and constituted the RNAi (TGM2-shRNA) group. A control (NC) group was also established by transfecting MDA-MB-231 cells with scrambled shRNA. The expression levels of TG2, E-cadherin, vimentin and B-cell lymphoma (Bcl)-2 in the cells were examined via western blotting. The transfected MDA-MB-231 cells were divided into four groups, two of which were treated with doxetaxel (TXT): NC, RNAi, TXT and RNAi + TXT groups,. Cell proliferation was analyzed by MTT assay and cell apoptosis was detected by flow cytometry. An in vivo assay was also conducted, in which MDA-MB-231 cells transfected with scrambled shRNA or TGM2-shRNA were subcutaneously implanted into nude mice. After 2 weeks, TXT or vehicle was intraperitoneally administered at a dose of 10 mg/kg on day 1 of every week and tumor growth was monitored. Following the silencing of TGM2 in the MDA-MB-231 cells, the cells showed changes in morphology, indicating that an increased expression of TG2 was associated with a mesenchymal morphology. Transfection of the cells with TGM2-shRNA affected the expression of TG2, E-cadherin, vimentin and Bcl-2. In the MTT assay, the proliferation of MDA-MB-231 cells was significantly inhibited in the RNAi group compared with the control group (P<0.05), and the inhibitory effect increased in a time-dependent manner. Following treatment with TXT for 48 h, apoptosis was significantly promoted in the RNAi + TXT group compared with that in the other groups (P<0.05). Measurement of the tumors in the nude mice indicated that the combination of RNAi and TXT brought about a stronger antitumor effect than either treatment alone. These results suggest that the downregulation of TG2 reversed EMT and modulated the chemosensitivity of breast cancer to TXT. TG2 may be an important predictive and prognostic factor for the treatment efficacy of chemotherapy in patients with breast cancer. | Authentic |
Text : Family with sequence similarity three member C (FAM3C) (interleukin-like EMT inducer [ILEI]), heat shock factor 1 (HSF1) and Ying-Yang 1 (YY1) have been independently reported to be involved in the pathogenesis of various cancers. However, whether they are coordinated to trigger the development of cancer remains unknown. This study determined the role and mechanism of YY1 and HSF1 in FAM3C-induced proliferation and migration of breast cancer cells. In human MDA-MB-231 breast cancer cell line, transforming growth factor-β (TGFβ) up-regulated FAM3C, HSF1 and YY1 expressions. FAM3C overexpression promoted the proliferation and migration of MDA-MB-231 cells with YY1 and HSF1 up-regulation, whereas FAM3C silencing exerted the opposite effects. FAM3C inhibition repressed TGFβ-induced HSF1 activation, and proliferation and migration of breast cancer cells. YY1 was shown to directly activate HSF1 transcription to promote the proliferation and migration of breast cancer cells. YY1 silencing blunted FAM3C- and TGFβ-triggered activation of HSF1-Akt-Cyclin D1 pathway, and proliferation and migration of breast cancer cells. Inhibition of HSF1 blocked TGFβ-, FAM3C- and YY1-induced proliferation and migration of breast cancer cells. YY1 and HSF1 had little effect on FAM3C expression. Similarly, inhibition of HSF1 also blunted FAM3C- and TGFβ-promoted proliferation and migration of human breast cancer BT-549 cells. In human breast cancer tissues, FAM3C, YY1 and HSF1 protein expressions were increased. In conclusion, FAM3C activated YY1-HSF1 signalling axis to promote the proliferation and migration of breast cancer cells. Furthermore, novel FAM3C-YY1-HSF1 pathway plays an important role in TGFβ-triggered proliferation and migration of human breast cancer MDA-MB-231 cells. | Authentic |