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Text : Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon (CVM), for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood-brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained (some dye observed in the liver was transient, likely representing degradation products). Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit. | Authentic |
Text : To implement Knowledge Based (KB) automatic planning for right and left-sided whole breast treatment through a new volumetric technique (ViTAT, Virtual Tangential-fields Arc Therapy) mimicking conventional tangential fields (TF) irradiation. A total of 193 clinical plans delivering TF with wedged or field-in-field beams were selected to train two KB-models for right(R) and left(L) sided breast cancer patients using the RapidPlan (RP) tool implemented in the Varian Eclipse system. Then, a template for ViTAT optimization, incorporating individual KB-optimized constraints, was interactively fine-tuned. ViTAT plans consisted of four arcs (6 MV) with start/stop angles consistent with the TF geometry variability within our population; the delivery was completely blocked along the arcs, apart from the first and last 20° of rotation for each arc. Optimized fine-tuned KB templates for automatic plan optimization were generated. Validation tests were performed on 60 new patients equally divided in R and L breast treatment: KB automatic ViTAT-plans (KB-ViTAT) were compared against the original TF plans in terms of OARs/PTVs dose-volume parameters. Wilcoxon-tests were used to assess the statistically significant differences. KB models were successfully generated for both L and R sides. Overall, 1(3%) and 7(23%) out of 30 automatic KB-ViTAT plans were unacceptable compared to TF for R and L side, respectively. After the manual refinement of the start/stop angles, KB-ViTAT plans well fitted TF-performances for these patients as well. PTV coverage was comparable, while PTV D1% was improved with KB-ViTAT by R:0.4/L:0.2 Gy (p < 0.05); ipsilateral OARs Dmean were similar with a slight (i.e., few % volume) improvement/worsening in the 15-35 Gy/2-15 Gy range, respectively. KB-ViTAT better spared contralateral OARs: Dmean of contralateral OARs was 0.1 Gy lower (p < 0.05); integral dose was R:5%/L:8% lower (p < 0.05) than TF. The overall time for the automatic plan optimization and final dose calculation was 12 ± 2 minutes. Fully automatic KB-optimization of ViTAT can efficiently replace manually optimized TF planning for whole breast irradiation. This approach was clinically implemented in our institute and may be suggested as a large-scale strategy for efficiently replacing manual planning with large sparing of time, elimination of inter-planner variability and of, seldomly occurring, sub-optimal manual plans. | Authentic |
Text : Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix‑loop‑helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis‑related markers in human esophageal squamous cell carcinoma TE‑11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively. Following cisplatin treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited expression of the pro‑apoptotic factor Bim and slightly increased the anti‑apoptotic factor Bcl‑xL. However, overexpression of DEC1 during cisplatin treatment failed to affect expression of these markers. Additionally, overexpression of DEC2 improved cell viability and decreased cell apoptosis induced by cisplatin. These results suggested that DEC2 exhibits anti‑apoptotic effects in TE‑11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may therefore have therapeutic potential for the treatment of esophageal cancer, in combination with cisplatin. | Authentic |
Text : To examine the effects of 3D printing model in total en bloc spondylectomy (TES). We performed a retrospective chart review of 41 cases of spinal tumors at our institution between 2017 and 2020, in which TES was applied. There were 19 cases with 3D printing model and 22 cases without 3D printing model. Operation time, intraoperative blood loss, excision range, complications, VAS, and ASIA grades were recorded. Statistical methods were used to analyze the data. KaplanMeier survival curve was made to evaluate the survival. There were significant differences in intraoperative blood loss between the two groups. The rate of R0 resection and tumor envelope preservation were higher in 3D group than that in non-3D group. In 3D group, the complications included surgical site infection (5.2%) and cerebrospinal fluid leak (15.7%). In non-3D group, the complications included cerebrospinal fluid leak (27.3%) and nerve root injury (13.6%). The pain and neurological dysfunction were significantly relieved before and after surgery in 3D group. However, the neurological relief in non-3D group patients was not complete. The VAS scores of non-3D group at 6 months after surgery were much higher than that of 3D group. The application of 3D printing model not only helps surgeons observe the morphology, invasion range, and anatomic relationship of the tumor preoperatively, but also assists surgeons to judge, locate, and separate the tumor intraoperatively. For spinal malignancies, the 3D printing model is worth promoting. | Authentic |
Text : This study aimed to analyze the impact of microRNA-499 (miR-499) on the inflammatory damage of endothelial cells during coronary artery disease (CAD) via the targeting of PDCD4 through the NF-kB/ TNF-α signaling pathway. A total of 216 CAD patients (CAD group) and 90 healthy people (normal group) were enrolled in our study. Endothelial cells were collected and assigned into normal, OX-LDL, negative control (NC), miR-499 inhibitor, miR-499 mimic, PDCD4 siRNA, and miR-499 inhibitor + PDCD4 siRNA groups. The qRT-PCR and western blotting were performed to detect the mRNA and protein expression levels of PDCD4 and miR-499. The MTT assay was performed to determine cell viability, ELISA was performed to determine the expression levels of inflammatory factors, and flow cytometry assay to evaluate cell apoptosis. Increased miR-499 expression and decreased PDCD4 expression in the plasma were observed in the CAD group compared with the normal group, demonstrating a negative correlation between miR-499 and PDCD4. Compared to the normal and miR-499 inhibitor groups, the survival rate of cells and PDCD4 expression were decreased; and the expressions of miR-499, IL-6, IL-8, IL-1β, TNF-α, NF-kB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all elevated in the OX-LDL, NC, miR-499 mimic, PDCD4 siRNA and miR-499 inhibitor + PDCD4 siRNA groups. Compared to the OX-LDL, NC and miR-499 inhibitor + PDCD4 siRNA groups, PDCD4 expression and the survival rate of cells were increased; and the IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 expression levels and the apoptosis rate were all reduced in the miR-499 inhibitor group. In the PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were lower, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all higher compared with the miR-499 mimic group. In the miR-499 inhibitor + PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were higher, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1, and MCP-1 and the apoptosis rate were all lower than those in the PDCD4 siRNA group. Down-regulated miR-499 expression increased PDCD4 expression and protected endothelial cells from inflammatory damage during CAD by inhibiting the NF-κB/TNF-α signaling pathway. | Counterfeit |
Text : Patients receiving cancer chemotherapy may experience a number of potentially severe adverse drug reactions. It is crucial for all members of the health care team to monitor the effect of medicines on the patient to ensure the safety and efficacy of the chemotherapy. The present study prepared medication instruction sheets (MISs) on hematological malignancy and conducted a questionnaire survey to verify their usefulness among physicians, dentists, and nurses. MISs were prepared for 103 chemotherapy and 44 pretreatment regimens for hematopoietic stem cell transplantation in the Department of Hematology at Kyushu University Hospital. Eight questions were prepared to investigate whether MISs could help physicians, dentists, and nurses manage cancer chemotherapy more safely, effectively, and efficiently, as well as in the sharing of information. A total of 35 medical staff working in inpatient wards, including 8 physicians, 3 dentists, and 24 nurses, participated in the questionnaire survey. All of the staff responded to the questionnaire survey, which showed that the MISs were favorably accepted by the participants. There was no negative opinion on the management of chemotherapy using the MISs. The MIS was a useful tool for sharing information on cancer chemotherapy between patients and medical staff and for enabling efficient management, thereby improving the safety and efficacy of treatment. | Authentic |
Text : Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal acute mortality and chronic nervous system injury. Recently, it has been found that long noncoding RNAs (lncRNAs) play a significant role in the neurodevelopment and etiopathogenesis of HIBD. Here, the researchers aimed to determine the role of lncRNA maternally expressed gene (MEG3) in the therapeutic effect of dexmedetomidine (DEX) in neonatal mice with HIBD through the regulation of microRNA-129-5p (miR-129-5p). HIBD models were established in C57/BL6 neonatal mice. Subsequently, the target relationship between MEG3 and miR-129-5p was predicted and verified. The neonatal mice were injected with DEX, ad-shMEG3, and mimics and inhibitors of miR-129-5p to identify roles of MEG3 and miR-129-5p in therapeutic effects of DEX on neuronal apoptosis and injury, cerebral atrophy, and learning and memory ability of neonatal mice with HIBD. MEG3 directly targeted and inhibited the expression of miR-129-5p. Silencing of MEG3 or upregulation of miR-129-5p effectively promoted the therapeutic effect of DEX on neonatal mice with HIBD. Silencing of MEG3 or upregulation of miR-129-5p reduced the neuronal apoptosis rate and degree of cerebral atrophy, and also enhanced the learning and memory ability of HIBD neonatal mice. Collectively, the key findings obtained from the present study support the notion that MEG3 silencing enhances the therapeutic effect of DEX on neonatal mice with HIBD by binding to miR-129-5p. | Counterfeit |
Text : The outcome of prostate cancer (PCa) patients is highly variable and depends on whether or not distant metastases occur. Multiple chromosomal deletions have been linked to early tumor marker PSA recurrence (biochemical relapse, BCR) after radical prostatectomy (RP), but their potential role for distant metastasis formation is largely unknown. Here, we specifically analyzed whether deletion of the tumor suppressor CHD1 (5q21) influences the post-surgical risk of distant metastasis and whether CHD1 loss directly contributes to metastasis formation in vivo. By considering >6800 patients we found that the CHD1 deletion negatively influences metastasis-free survival in R0 patients (HR: 2.32; 95% CI: 1.61, 3.33; p < 0.001) independent of preoperative PSA, pT stage, pN status, Gleason Score, and BCR. Moreover, CHD1 deletion predicts shortened BCR-free survival in pT2 patients and cancer-specific survival in all patients. In vivo, CHD1 loss increases spontaneous pulmonary metastasis formation in two distinct PCa models coupled with a higher number of multicellular colonies as compared to single-cell metastases. Transcriptome analyses revealed down-regulation of the PCa-specific metastasis suppressor and TGFβ signaling regulator PMEPA1 after CHD1 depletion in both tested PCa models. CHD1 loss increases the risk of postoperative metastasis in R0-resected PCa patients and promotes spontaneous metastasis formation in vivo. | Authentic |
Text : Hypopharyngeal carcinoma is one of the most aggressive subtypes of squamous cell carcinoma of the head and neck. Although significant progress has been made in surgical techniques, radiotherapy, and chemotherapy, the prognosis is still poor. Mesenchymal stem cells (MSCs) have attracted substantial attention as tumor-targeted cellular carriers for cancer gene therapy. We have previously shown that recombinant baculovirus-adeno-associated vectors (BV-AAV) possessed high efficiency for multi-gene coexpression in human bone marrow MSCs (BMSCs) and BV-AAV-engineered BMSCs could effectively target hypopharyngeal cancer tissues in vivo. However, it was not clear whether BV-AAV-engineered BMSCs as cellular vehicles, mediating the expression of the sodium iodide symporter (NIS), would be effective in controlling the growth of hypopharyngeal carcinoma by radioiodine therapy. We constructed a hybrid BV-AAV containing the Luc-P2A-eGFP fusion or NIS sequence to modify BMSCs (BMSCs-Bac-Luc-P2A-eGFP or BMSCs-Bac-NIS). The 125I uptake of BMSCs-Bac-NIS was analyzed by an automatic gamma counter in vitro and micro-single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging in vivo. The value of radioiodine therapy for hypopharyngeal carcinoma was evaluated by measuring tumor volume, glucose metabolism (via 2-deoxy-2-[18F] glucose [18F-FDG] positron emission tomography/CT), and proliferation of tumor cells. We demonstrated that 125I uptake of BMSCs-Bac-NIS persists over long-term in vitro (at least 8 h). Radioactive uptake could be detected by SPECT/CT 1 h after 125I injection in the BMSCs-Bac-NIS group, showing that this strategy allows for the tracking of real-time migration and transgene expression of BMSCs. Radioiodine therapy resulted in a significant reduction in tumor growth (386.93 ± 249.23 mm3 vs 816.56 ± 213.87 mm3 in controls), increased survival, and decreased SUVmax of 18F-FDG. The hybrid BV-AAV that can provide a variety of genes and regulatory elements, as a novel gene therapy strategy opens the prospect of NIS-mediated radionuclide therapy of hypopharyngeal carcinoma after MSC-mediated gene delivery. | Authentic |
Text : Poly (ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and are involved in a variety of biological processes. PARP6 is a novel member, and our previous findings suggest that PARP6 may act as a tumor suppressor via suppressing cell cycle progression. However, it is still unclear that PARP6 function besides growth suppression in colorectal cancer (CRC). In this study, we examined tumor suppressive roles of PAPR6 in CRC cells both in vitro and in vivo. We found that PARP6 inhibited colony formation, invasion and migration as well as cell proliferation. Moreover, ectopic overexpression of PARP6 decreased Survivin expression, which acts as an oncogene and is involved in apoptosis and mitosis. We confirmed the inverse correlation between PARP6 and Survivin expression in CRC cases by immunohistochemistry. Importantly, CRC cases with downregulation of PARP6 and upregulation of Survivin showed poor prognosis. In summary, PARP6 acts as a tumor suppressor via downregulating Survivin expression in CRC. PARP6 can be a novel diagnostic and therapeutic target together with Survivin for CRC. | Authentic |
Text : Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Treatments include glucocorticoids (GCs) such as dexamethasone (Dex) and prednisolone, which may be of value when used alongside cytotoxic anti-cancer drugs. To predict therapeutic efficacy of GCs, their activity against ALL cells is usually examined prior to chemotherapy; however, few studies have examined their effects when used in combination with other drugs. The paradox is that cytotoxic anti-cancer drugs that are effective against proliferating cancer cells show synergistic effects when used with GCs that prevent cell proliferation. To address this point, we investigated intracellular energy metabolism in ALL CCRF-CEM cell clones classified according to their sensitivity to Dex and cytotoxic anti-cancer drugs in bulk cultures of mixed cells. We found that Dex suppressed glycolysis, the most important metabolic system in cancer cells, in cells that were damaged by etoposide (a cytotoxic anti-cancer drug), and the cells showed a concomitant increase in mitochondrial oxidative phosphorylation. Furthermore, autophagy, an intracellular bulk degradation system, regulated mitochondrial viability. We also found that mitochondria, whose function is enhanced by Dex, were susceptible to anti-cancer drugs that inhibit respiratory complexes (e.g., etoposide and daunorubicin), resulting in increased production of reactive oxygen species and subsequent cytotoxicity. Taken together, the present study points the way toward a more accurate prediction of the sensitivity of ALL cells to the combined action of anti-cancer drugs and GCs, by taking into consideration the shift in intracellular energy metabolism caused by GCs: namely, from glycolysis to mitochondrial oxidative phosphorylation mediated by autophagy. | Authentic |
Text : To investigate the anticancer activity of bornyl acetate and its combination with low dose 5-fluorouracil (5-FU) in human gastric cancer (SGC-7901) cells and to evaluate their effects on cell cycle, apoptosis, cancer cell morphology and DNA fragmentation. The anticancer activity of bornyl acetate, 5-FU and their combination against human gastric cancer (SGC-7901) cells was evaluated by MTT assay. Flow cytometry using propidium iodide (PI) as a staining agent was used to study the effect of the extract on cell cycle phase distribution. Apoptosis induced by bornyl acetate and 5-FU was evaluated by Annexin V binding assay using flow cytometer. Alterations in cell morphology following apoptosis was studied by fluorescence microscopy as well as transmission electron microscopy. Bornyl acetate induced dose-dependent growth inhibitory effects on human gastric cancer cells in vitro.The combination of bornyl acetate with 5-FU induced a much more growth inhibitory effect on these cells indicating a synergistic enhancement of anticancer activity of 5-FU. The combined effect of bornyl acetate and 5-FU also resulted in greater apoptosis induction as well as cell cycle arrest in comparison to the individual treatment by bornyl acetate or 5-FU. Fluorescence microscopy as well as transmission electron microscopy also revealed that the combination of bornyl acetate with 5-FU resulted in greater apoptosis induction as well as cell morphology alterations. The percentages of early as well as late apoptotic cells were much higher in the combination treatment in comparison to separate treatment by bornyl acetate or 5-FU. Bornyl acetate potentiates the anticancer activity of 5-FU in human gastric cancer (SGC-7901) cells by inducing apoptosis, DNA fragmentation as well as G2/M cell cycle arrest. | Counterfeit |
Text : Mediator complex subunit 19 (Med19), a RNA polymerase II-embedded coactivator, is reported to be involved in bladder cancer (BCa) progression, but its functional contribution to this process is poorly understood. Here, we investigate the effects of Med19 on malignant behaviours of BCa, as well as to elucidate the possible mechanisms. Med19 expression in 15 BCa tissues was significantly higher than adjacent paired normal tissues using real-time PCR and Western blot analysis. Immunohistochemical staining of 167 paraffin-embedded BCa tissues was performed, and the results showed that high Med19 protein level was positively correlated with clinical stages and histopathological grade. Med19 was knocked down in BCa cells using short-hairpin RNA. Functional assays showed that knocking-down of Med19 can suppress cell proliferation and migration in T24, UM-UC3 cells and 5637 in vitro, and inhibited BCa tumour growth in vivo. TOP/FOPflash reporter assay revealed that Med19 knockdown decreased the activity of Wnt/β-catenin pathway, and the target genes of Wnt/β-catenin pathway were down-regulated, including Wnt2, β-catenin, Cyclin-D1 and MMP-9. However, protein levels of Gsk3β and E-cadherin were elevated. Our data suggest that Med19 expression correlates with aggressive characteristics of BCa and Med19 knockdown suppresses the proliferation and migration of BCa cells through down-regulating the Wnt/β-catenin pathway, thereby highlighting Med19 as a potential therapeutic target for BCa treatment. | Authentic |
Text : Numerous in vitro and in vivo studies have demonstrated that calcitriol [1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity, regulating proliferation, differentiation and apoptosis, as well as angiogenesis. Vitamin D compounds have been shown to exert synergistic effects when used in combination with different agents used in anticancer therapies in different cancer models. The aim of this study was to evaluate the mechanisms of the cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI‑2191) and 1,25(OH)2D3] with tyrosine kinase inhibitors (imatinib and sunitinib) together with cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer model. The cytotoxic effects of the test compounds used in different combinations were evaluated on A549 lung cancer cells, as well as on human lung microvascular endothelial cells (HLMECs). The effects of such combinations on the cell cycle and cell death were also determined. In addition, changes in the expression of proteins involved in cell cycle regulation, angiogenesis and the action of vitamin D were analyzed. Moreover, the effects of 1,24(OH)2D3 on the anticancer activity of sunitinib and sunitinib in combination with docetaxel were examined in an A549 lung cancer model in vivo. Experiments aiming at evaluating the cytotoxicity of the combinations of the test agents revealed that imatinib and sunitinib together with cisplatin or docetaxel exerted potent anti-proliferative effects in vitro on A549 lung cancer cells and in HLMECs; however, 1,24(OH)2D3 and 1,25(OH)2D3 enhanced the cytotoxic effects only in the endothelial cells. Among the test agents, sunitinib and cisplatin decreased the secretion of vascular endothelial growth factor (VEGF)‑A from the A549 lung cancer cells. The decrease in the VEGF‑A level following incubation with cisplatin correlated with a higher p53 protein expression, while no such correlation was observed following treatment of the A549 cells with sunitinib. Sunitinib together with docetaxel and 1,24(OH)2D3 exhibited a more potent anticancer activity in the A549 lung cancer model compared to double combinations and to treatment with the compounds alone. The observed anticancer activity may be the result of the influence of the test agents on the process of tumor angiogenesis, for example, through the downregulation of VEGF‑A expression in tumor and also on the induction of cell death inside the tumor. | Authentic |
Text : Astrocytomas are diffusible infiltrative and aggressive brain tumors that are extensive and heterogeneous clusters of neoplastic growths in the central nervous system (CNS). Meningioma tumors are commonly benign but may demonstrate an invasive pattern with frequent recurrences. Human telomerase reverse transcriptase (hTERT) is an unfavorable prognostic factor for several types of cancers, and there are controversies about its role. In the present study, we investigated the relative expression of hTERT splice variants in 2 groups of brain tumors compared to non-tumor samples. The mRNA of 40 brain tumor samples and 4 control samples was extracted; mRNA expression of hTERT α-deletion and β-deletion variants, as well as the wild type isoform, was quantified using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The α-deletion variant was significantly expressed in primary benign meningeal tumors (p = 0.01). The results indicate a positive correlation between the relative expression of hTERT mRNA transcript and α-deletion and β-deletion variants in both groups of tumors (meningiomas and astrocytomas). A strong association between the expression of the full-length splice variant and the β-deletion variant was observed in astrocytoma tumors (p = 0.045). The most significant correlations were found between the hTERT full-length and β-deletion variants in high-grade meningiomas (p = 0.018, correlation coefficient (CC) = 0.964) and grade II astrocytomas (p = 0.015; CC = 0.580). In addition, in low grades of both types of tumors, the hTERT full-length variant and especially the α-deletion variant were the predominant isoforms. The overexpression of hTERT and β-deletion variants in high grades of these tumors was statistically significant. Our findings indicate that α-deletion and β-deletion isoforms are associated with high levels of full-length hTERT mRNA in both groups of brain tumor patients. Changes in the splicing pattern of hTERT splice variants in brain tumors and their correlation with pathological alterations in cells could be applied as diagnostic or prognostic biomarkers, or possibly as targets for cancer therapy. However, the function and biological role of hTERT splice variants remain to be clarified. | Authentic |
Text : Energy metabolism in carcinogenesis is poorly understood. It is widely accepted the majority of colorectal cancers (CRCs) arise from adenomatous polyps (APs). We aimed to characterize the bioenergetic alterations in APs and CRCs. Fifty-six APs, 93 CRCs and adjacent normal mucosae were tested. Oxygen consumption rate (OCR) was measured representing mitochondrial oxidative phosphorylation (OxPhos), and extracellular acidification rate (ECAR)was measured representing glycolysis. Mitochondrial DNA (mtDNA) variants and mutations were studied. Over-expressed metabolic genes in APs were identified by microarray and validated by qRT-PCR, Western blots and immunohistochemistry. Identified genes were knocked down in WiDr and colo205 CRC cell lines, and their expression was analyzed in APs/CRCs with enhanced glycolysis. ECAR, not OCR, was significantly increased in APs. While no difference of ECAR was found between CRCs and normal mucosae, OCR was significantly reduced in CRCs. OCR/ECAR ratio was decreased in APs over 1 cm, APs with a villous component and CRCs, indicating their glycolytic tendencies. The number of mtDNA mutations was increased in APs and CRCs, but not correlated with metabolic profiles. Two metabolic genes ALDOB and SLC16A4 were up-regulated in APs. Both ALDOB-knockdown and SLC16A4-knockdown CRC cell lines showed increased basal motichondrial OxPhos and decreased basal glycolysis. Moreover, the increase of mitochondrial ATP-linked respiration and the decrease of glycolytic capacity were showed in SLC16A4-knockdown cells. Finally, APs/CRCs with enhanced glycolysis had increased SLC16A4 expression. ATP production shifts from OxPhos to glycolysis in the process of AP enlargement and villous transformation. OxPhos defects are present in CRCs but not in APs. APs and CRCs tend to accumulate mtDNA mutations, but these are not correlated with bioenergetic profiles. Finally, the ALDOB and SLC16A4 may contribute to the glycolytic shift in APs/CRCs. | Authentic |
Text : Traditionally, Ehrlich's tumor is used in experimental oncology to investigate the therapeutic capacity of different synthetic chemotherapeutic agents or to evaluate the antitumoral activity of different substances of natural origin. However, the understanding of immune mechanisms during Ehrlich carcinogenesis is still limited. In this review, we seek to describe the immune response during Ehrlich's tumor growth, and natural response without the influence of pharmacological administration, immunotherapies or concomitant challenges. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A systematic review was carried out that included experimental trials with mice challenged with Ehrlich's tumor. The research was carried out in three databases including MEDLINE/PubMed, Scopus, Latin American and Caribbean Literature in Health Sciences (LILACS). The searches resulted in 913 papers being found, of which 55 articles were considered eligible, and of these 55, 29 were selected for analysis. Findings indicate that there is an increase in the expression of M2 and T Helper (TH2) macrophages and of the cytokines IL-17, IL-1B, IL-6 and PGE in the ascitic form of Ehrlich. These phenotypic expressions are also found in ascitic neoplasms in humans. Ehrlich's solid tumor was characterized by increased expression of CD4, CD8, neutrophils and TNF-a, Foxp3 + and Qa-2 +, and these characteristics are analogous to human breasts cancers. It is our understanding that further studies are needed to assess the immune mechanisms in Ehrlich's tumor, since these findings can be used to improve cancer treatments that are analogous to Ehrlich's tumor. | Authentic |
Text : Since the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis. A GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis. miR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p. The plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients. | Authentic |
Text : The importance of circular RNAs in malignant tumors causes more attention in researchers. Hepatocellular carcinoma (HCC) is one of the most ordinary malignant tumors. Hsa_circ_0000285 was explored to identify how it functions in the metastasis of HCC. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect hsa_circ_0000285 expression in HCC patients' tissues. Hsa_circ_0000285 lentivirus and shRNA was constructed for the transfection of HCC cells. Wound healing assay, transwell assay, and Matrigel assay were conducted to identify the function of hsa_circ_0000285 in HCC cells. Furthermore, mechanism assays were performed to uncover the interaction between hsa_circ_0000285 and miR-599. Hsa_circ_0000285 was significantly higher-expressed in HCC samples compared to that in adjacent samples. The migrated length of HCC cells was reduced after hsa_circ_0000285 was silenced, while the migrated length of HCC cells was increased after hsa_circ_0000285 was overexpressed. Moreover, the number of migrated and invaded HCC cells was reduced after hsa_circ_0000285 was silenced, while the number of migrated and invaded HCC cells was increased after hsa_circ_0000285 was overexpressed. Moreover, RT-qPCR results revealed that miR-599 was downregulated via overexpression of hsa_circ_0000285, while miR-599 was upregulated via knockdown of hsa_circ_0000285. Further experiments showed that miR-599 was a direct target of hsa_circ_0000285 in HCC. Hsa_circ_0000285 could enhance cell metastasis of HCC by targeting miR-599 and might be a potential therapeutic target in HCC. | Counterfeit |
Text : Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) is a nucleo-cytoplasmic shuttling protein, and its expression is associated with cancer aggressiveness. However, the role of HPIP in ovarian cancer is still unclear. Here, we aimed to clarify the role of HPIP in epithelial-mesenchymal transition (EMT) process of ovarian cancer cells, stimulated by transforming growth factor (TGF)-β1. In this study, we found that HPIP was highly expressed in ovarian cancer cells, and TGF-β1 treatment induced HPIP expression in ovarian cancer cells. In addition, knockdown of HPIP suppressed TGF-β1-induced EMT and migration/invasion in ovarian cancer cells. Moreover, knockdown of HPIP significantly blocked the phosphorylated pattern of both PI3K and Akt induced by TGF-β1 in SKOV3 cells. In conclusion, the present study showed that HPIP silencing might prevent TGF-β1-induced EMT in ovarian cancer cells. Thus, HPIP may be a potential therapeutic target for the treatment of ovarian cancer. | Authentic |
Text : ZCCHC14 is a CCHC-type zinc finger protein which is expressed in tissues in human and mouse. The function of ZCCHC14 in tumours remains unclear. In this research, we explored the expression, function and related molecular mechanisms of ZCCHC14 in human non-small cell lung cancer (NSCLC). Immunochemistry staining showed that ZCCHC14 was low-expressed or absent in NSCLC tissues. In NSCLC patients, the low expression of ZCCHC14 in tumour tissues was significantly correlated with TNM stage, differentiation degree and adverse clinical outcome (P < .05). The proliferation and invasion ability of cancer cells transfected with ZCCHC14 CRISPR/Ca9 KO plasmids was significantly enhanced (P < .05). Immunoblotting analysis indicated that the expression of p-P38, cyclinD1 and MMP7 were significantly up-regulated after disabling ZCCHC14 (P < .05). We used MAPK-P38 pathway inhibitor doramapimod (BIRB 796) to inhibit P38 signalling pathway activity and determined that the agent significantly disrupted the function of ZCCHC14 and hindered the proliferation and invasion of the tumour. The finding revealed that ZCCHC14 can regulate proliferation and invasion of NSCLC through the P38 pathway. ZCCHC14 plays a crucial regulatory role in the development of NSCLC and may become a zinc finger target for clinical treatment. | Authentic |
Text : Helicobacter pylori (HP) infection has been demonstrated to be a risk factor accounting for the initiation and development of gastric cancer (GC). The aim of the present study was to investigate the clinical significance of miR-490-3p in HP associated GC. We measured the expression level of miR-490-3p in human GC tissues by quantitative Real-time PCR (qPCR). Then the association between miR-490-3p and clinical features of GC was further investigated. Our results showed that miR-490-3p levels exhibited a progressive downregulation in gastritis, intestinal metaplasia, HP negative GC and HP positive GC. In addition, miR-490-3p expression was significantly correlated with various clinicopathological parameters such as lymph node metastasis and clinical stage in HP-positive GC. Moreover, GC patients with lower miR-490-3p had a shorter 5 years overall/disease free survival time in the HP positive cohort. Finally, multivariate analysis showed that low miR-490-3p was an independent risk factor for HP associated GC. miR-490-3p is downregulated in HP-positive GC and associated with poor clinical outcome, indicating that miR-490-3p is a promising prognostic biomarker for HP positive GC. | Authentic |
Text : In previous years, studies have shown that Astragalus polysaccharides (APS) can improve cellular immunity and humoral immune function, which has become a focus of investigations. Tumor necrosis factor‑α‑induced protein 8‑like 2 (TIPE2) is a negative regulator of immune reactions. However, the effect and underlying mechanisms of TIPE2 on the APS‑induced immune response remains to be fully elucidated. The present study aimed to examine the role of TIPE2 and its underlying mechanisms in the APS‑induced immune response. The production of nitric oxide (NO) was detected in macrophages in vitro following APS stimulation. In addition, the present study interfered with the expression of TIPE2 in macrophages, and examined the production of cytokines, NO and components of the mitogen‑activate protein kinase (MAPK) signaling pathway following APS stimulation. The results showed that APS was able to activate macrophages by inducing the production of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑6 and NO. Furthermore, RAW264.7 cells were stimulated with APS when TIPE2 was silenced, and it was found that the production of TNF‑α, IL‑6, IL‑1β and NO were upregulated, and the signaling pathway of MAPK was activated. Taken together, these results demonstrated that TIPE2 had an important negative effect on the APS‑induced production of inflammatory cytokines and NO via the MAPK signaling pathway. | Authentic |
Text : The aim of this study was to explore the expression of Livin in benign and malignant parotid gland tumors. We also investigate the role of Livin in the occurrence and progression of parotid gland tumors. Livin expression in 30 cases of normal parotid gland tissues, 40 cases of benign parotid gland tumors and 60 cases of malignant parotid gland tumors was detected by immunohistochemistry. The correlation between Livin expression and pathological characteristics of patients with parotid gland tumors was analyzed. The differentially expressed Livin in normal parotid gland tissues and malignant parotid gland tumors was determined by Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. Livin expression was unable to be detected in normal parotid gland tissues. The positive rate of Livin expression in benign and malignant parotid gland tumors was 17.50% and 71.67%, respectively (p<0.05). Livin expression was correlated to malignant level, clinical stage and tumor diameter in 60 cases of malignant parotid gland tumors (p<0.05). However, the positive rate of Livin expression was not correlated to lymph node metastasis, age and sex of patients with parotid gland tumors (p>0.05). Livin expression is closely related to the pathological progression of parotid gland tumors, which may serve as a hallmark in diagnosis, treatment and prognosis of patients with parotid gland tumors. | Authentic |
Text : Early prediction of outcome is important for allocation of therapeutic strategies. Endocrine alterations of the hypothalamus-pituitary-axis are one of the first stress-induced alterations after cerebral ischemia. We therefore evaluated the prognostic value of serum cortisol in Chinese patients with an acute ischemic stroke. In a prospective observational study, serum cortisol was measured using a solid-phase, competitive chemiluminescent enzyme immunoassay on admission in serum of 226 consecutive Chinese patients with an acute ischemic stroke. The prognostic value of serum cortisol to predict the functional outcome, mortality within 90 days, was compared with clinical variables (e.g., advanced age and the National Institutes of Health Stroke Scale [NHISS] score) and with other known predictors. Patients with a poor outcome and nonsurvivors had significantly increased serum cortisol levels on admission (P<0.0001, P<0.0001). There was a positive correlation between levels of cortisol and the NIHSS (r = 0.298, P<0.0001), glucose levels (r = 0.324, P<0.0001) and infarct volume (r = 0.328, P<0.0001). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio 3.44 (2.58-6.23) and 4.21 (1.89-9.24), respectively, P<0.0001 for both, adjusted for age, the NIHSS and other predictors] in patients with ischemic stroke. In receiver operating characteristic curve analysis, cortisol could improve the NIHSS score in predicting short-term functional outcome (Area under the curve [AUC] of the combined model, 0.87; 95% CI, 0.82-0.92; P = 0.01) and mortality (AUC of the combined model, 0.90; 95% CI, 0.84-0.95; P = 0.01). Cortisol can be seen as an independent short-term prognostic marker of functional outcome and death in Chinese patients with acute ischemic stroke even after correcting confounding factors. Combined model can add significant additional predictive information to the clinical score of the NIHSS. | Counterfeit |
Text : In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are powerful factors influencing the progression of multiple malignancies. Although a relationship between the lncRNA NEAT1 (nuclear enriched abundant transcript 1) and colorectal cancer has previously been reported, the functional mechanism underlying the involvement of NEAT1 in colorectal cancer remains unknown. In this study, we report that NEAT1 expression is up-regulated in colorectal cancer tissues, which correlates with advanced clinical features, poor overall survival and disease free survival. Up-regulated NEAT1 promotes cell proliferation and metastasis of colorectal cancer both in vitro and in vivo. Moreover, NEAT1 functions as an oncogene influencing cell viability and invasion in part by serving as a competing endogenous RNA (ceRNAs) modulating miRNA-34a expression, leading to subsequent repression of the miR-34a/SIRT1 axis and activation of the Wnt/β-catenin signaling pathway. Taken together, our study demonstrates that the lncRNA NEAT1 may serve as a prognostic biomarker and a potential therapeutic target in colorectal cancer. | Authentic |
Text : Increasing studies reported that the serum- and glucocorticoid-inducible kinases (SGKs) contributed to the tumorigenesis of various cancer. In this article, we are aiming to explore the function of SGK2 in renal cell cancer (RCC). In this study, the SGK2 expression was quantified by Western blot (WB) in multiple RCC cell lines. And in vitro SGK2 knockdown and overexpression experiments were also performed. In addition, molecular function analysis was performed using FunRich software V3. The Cancer Genome Atlas (TCGA) database was retrieved to verify the association between the SGK2 expression and the prognosis of RCC patients. We found that SGK2 was up-regulated in RCC tissues compared with adjacent normal tissues, and the SGK2 expression also increased in various RCC cell lines compared to that in the normal epithelial cell line HK-2. Meanwhile, the SGK2 expression was significantly associated with the survival rate of RCC patients. Functional experiments showed that silencing SGK2 expression inhibited RCC cells proliferation, migration, colony formation and invasion abilities in vitro, whereas opposite results were uncovered after overexpressing SGK2 in RCC cells. Furthermore, functional analyses showed that SGK2 related genes were associated with protein serine/threonine kinase activity, guanosine triphosphatase (GTPase) activity, guanyl-nucleotide exchange factor activity, and motor activity. Protein interaction analysis identified that growth factor receptor-bound protein 2 (GRB2), one of the most important upstream components in the growth factor signaling pathway, was significantly enriched in SGK2 related genes. In addition, the WB assay validated that SGK2 could promote the phosphorylation of ERK 1/2 and AKT. Our results suggested that SGK2 promoted RCC progression by mediating the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and Protein kinase B (AKT/PKB), indicating that SGK2 might serve as a potential prognostic marker and therapeutic target for renal cancer patients. | Authentic |
Text : Annexin A1 (ANXA1) is a Ca(2+)-binding protein over-expressed in pancreatic cancer (PC). We recently reported that extracellular ANXA1 mediates PC cell motility acting on Formyl Peptide Receptors (FPRs). Here, we describe other mechanisms by which intracellular ANXA1 could mediate PC progression. We obtained ANXA1 Knock-Out (KO) MIA PaCa-2 cells using the CRISPR/Cas9 genome editing technology. LC-MS/MS analysis showed altered expression of several proteins involved in cytoskeletal organization. As a result, ANXA1 KO MIA PaCa-2 partially lost their migratory and invasive capabilities with a mechanism that appeared independent of FPRs. The acquisition of a less aggressive phenotype has been further investigated in vivo. Wild type (WT), PGS (scrambled) and ANXA1 KO MIA PaCa-2 cells were engrafted orthotopically in SCID mice. No differences were found about PC primary mass, conversely liver metastatization appeared particularly reduced in ANXA1 KO MIA PaCa-2 engrafted mice. In summary, we show that intracellular ANXA1 is able to preserve the cytoskeleton integrity and to maintain a malignant phenotype in vitro. The protein has a relevant role in the metastatization process in vivo, as such it appears attractive and suitable as prognostic and therapeutic marker in PC progression. | Authentic |
Text : To study the effects of mind mapping combined with microvideo explanation on disease perception control and nursing cooperation during membrane induction therapy in patients with infectious nonunion after tibial trauma. 30 patients with infectious nonunion after tibial trauma treated in the hospital between March 2018 and March 2022 were selected as the research subjects, and the patients were divided into a control group (n = 15) and an observation group (n = 15) by the random number table method. During membrane induction therapy, the control group adopted a routine nursing method while the observation group was given a nursing method of mind mapping combined with microvideo explanation. The disease perception control, nursing cooperation, and self-care ability of the two groups of patients were compared. After nursing, the scores of aspects of "life impact (3.87 ± 0.92)," "duration (3.20 ± 1.01)," and "emotions (3.93 ± 0.59)" of the Brief Illness Perception Questionnaire (B-IPQ) in the observation group were lower than those in the control group (5.27 ± 0.88, 4.67 ± 1.05, and 4.93 ± 0.80, respectively) (P < 0.05) while the scores of "self-control (6.80 ± 1.21)" and "disease awareness (7.27 ± 0.70)" were higher than those in the control group (5.00 ± 1.07 and 5.93 ± 0.70, respectively) (P < 0.05). There was no significant difference in the total compliance rate between the two groups (P > 0.05). After nursing, the scores of dimensions and the total score of the Exercise of Self-Care Agency Scale (ESCA) were increased in the two groups, and the scores were higher in the observation group than those in the control group (P < 0.05). Mind mapping combined with microvideo explanation can improve the disease perception control during membrane induction therapy in patients with infectious nonunion after tibial trauma, improve the self-care ability, and facilitate the smooth progress of treatment. | Counterfeit |
Text : Tenascin-C (TNC), as a member of the extracellular matrix (ECM), plays an important role in cancer cell proliferation and migration and tumor invasion in various types of cancer. Here, we attempted to investigate the role of TNC as a prognostic factor in prostate cancer. We studied TNC expression via immunohistochemistry in 145 prostate cancer tissue samples. The clinicopathological relevance of TNC expression was examined, as well as other cancer-associated fibroblasts (CAFs)-related factors. Our results showed that the high levels of TNC expression in prostate cancer stroma was significantly associated with lymph node metastasis (P = 0.024) and clinical stage (P = 0.032). Furthermore, TNC was positively correlated with increased micro-vessel density (MVD) (P = 0.017) and tumor associated macrophage (TAM) population (P = 0.025). In both univariate and multivariate Cox regression analyses, TNC (P < 0.001) was an independent poor prognostic factor for overall survival in prostate cancer patients. Moreover, over-expression of TNC (P < 0.001), SMA (P = 0.042) and vimentin (P = 0.010) were significantly correlated with the lower overall survival. In addition, TNC expression in prostate cancer stroma was significantly associated with FSP1 (P = 0.011), SMA (P = 0.021), and vimentin (P = 0.002). In conclusion, our study revealed that high level of TNC as a potential biomarker of CAFs was significantly correlated with the poor prognosis for prostate cancer patients. | Authentic |
Text : Herein, a Mn(II) complex of the N,N'-dipyridoxyl(1,4-butanediamine) (═H2 L) Schiff base has been newly synthesized. The synthesized complex was characterized by several experimental methods. In addition, the density functional theory approaches were used for theoretical identification of the complex. A good agreement between the computed and experimental infrared frequencies demonstrates validity of the optimized geometry for the synthesized complex. In a N2 O2 manner, two azomethine nitrogens and two phenolate oxygens of the L2- ligand are coordinated to the Mn2+ metal ion. The biological studies indicate an efficient apoptotic and antioxidant activities of the synthesized [MnL(CH3 OH)2 ] complex on both of the HepG2 and MCF7 cancer cells. Since it has been suggested that the complex is an exclusive potent antitumor for treatment of the human breast and liver cancers. | Authentic |
Text : Cancer patients face multiple challenges, such as infertility caused by exposure to gonadotoxic agents and gonadal irradiation during cancer treatment. Little is known about the health practitioners' knowledge and practice regarding fertility preservation and its available options in Saudi Arabia. Thus, this study is designed to evaluate the level of knowledge, attitude, and practice (KAP) towards fertility preservation in cancer patients among health practitioners in an environmental region in Saudi Arabia. The cross-sectional study was carried out between September 2020 and January 2021. A self-administered questionnaire was distributed among health practitioners from a variety of specialties who work closely with cancer patients. Out of 100 participants, 90% need more knowledge about fertility preservation. The lack of fertility preservation clinics in the patient's area and its unaffordable expenses significantly influenced the health practitioners' attitude towards fertility preservation discussion with cancer patients. The results revealed that 92% of the participants agreed that the Saudi Ministry of Health should establish practice guidelines and provide fertility preservation services for cancer patients. The present study showed that clinical practitioners' knowledge remains insufficient. Education of health practitioners and the establishment of practice guidelines and fertility preservation clinics for cancer patients are required. | Authentic |
Text : The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that zinc pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear. Here we report that zinc pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro, selectively kills bone marrow cells from leukemia patients ex vivo, and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. This study has identified zinc pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor. | Authentic |
Text : Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune-related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1. We found IDO1 was significantly up-regulated in four gynaecologic cancers and breast cancer. According to breast cancer PAM50 classification scheme, IDO1 expression was higher in tumours of basal than other subtypes and showed better survival prognosis in BRCA and OV. Through immune infiltration analysis, we found a strong correlation between IDO1 and immune cell populations especially for dendritic cells and T cells. In addition, we investigated the association between IDO1 and tumour mutation burden (TMB) and found that IDO1 was significantly correlated with TMB in BRCA and CESC. GSVA revealed that hallmarks significantly correlated with IDO1 were involved in interferon gamma response, allograft rejection and inflammatory response. We also found PD-L1 and LAG3 were highly positive related to IDO1 in gynaecologic cancers when comparing with their corresponding normal tissues. Our results indicated that IDO1 participated in anti-tumour immune process and is correlated with mutation burden. These findings may expand our outlook of potential anti-IDO1 treatments. | Authentic |
Text : It has been reported that high-mobility group box 3 is overexpressed in various cancers. This study aimed to explore its function in non-small cell lung cancer (NSCLC). A546 and H460 cell lines were used for in vivo experiments, scratch healing tests, transwell migration and invasion experiments. It was first found that HMGB3 was highly expressed in tumor tissues in the patients and associated with NSCLC stage. Silencing of HMGB3 significantly slowed the growth, proliferation and invasion of NSCLC in vitro, and repressed cell growth in vivo. Mechanistic studies suggest that the observed effects were mediated by inhibiting the expression of β-catenin/MMP7/c-Myc in Wnt pathway. Our study highlights the role of HMGB3 in NSCLC, which may provide a therapeutic target for the treatment of NSCLC. | Authentic |
Text : Cortical neuron-released exosomes have been demonstrated to block inflammasome activation in the central nervous system. This study aimed to investigate whether cortical neuron-released exosomal microRNA-181c-3p (miR-181c-3p) affected ischemic brain injury (IBI). An IBI rat model was established by middle cerebral artery occlusion (MCAO). Astrocytes collected from rats were exposed to exosomes derived from cortical neurons to investigate the effect of exosomes on chemokine (C-X-C motif) ligand 1 (CXCL1) expression and inflammatory response. Then, ectopic expression was induced in astrocytes treated with oxygen and glucose deprivation (OGD). CXCL1 was identified to be an upregulated gene in IBI by microarray-based gene expression profiling. Additionally, upregulation of CXCL1 and promoted inflammatory response was also found in MCAO rats. miR-181c-3p was downregulated in OGD-treated cortical neurons and exosomes derived from OGD-treated cortical neurons. Exosomes derived from OGD-treated cortical neurons decreased the expression of CXCL1 and inflammatory factors in astrocytes, and exosomes delivered miR-181c-3p to decrease CXCL1 expression in astrocytes. CXCL1 was a target gene of miR-181c-3p. Delivery with miR-181c-3p mimic and siRNA against CXCL1 (si-CXCL1) was shown to inhibit inflammation in astrocytes by downregulating CXCL1. Collectively, exosomal miR-181c-3p derived from cortical neurons exerts protective effects on neuroinflammation in astrocytes via downregulation of CXCL1 in an IBI rat model. | Counterfeit |
Text : Ran (Ras-related nuclear protein) GTPase is a member of the Ras superfamily. Like all the GTPases, Ran cycles between an active (GTP-bound) and inactive (GDP-bound) state. However, Ran lacks the CAAX motif at its C-terminus, a feature of other small GTPases that ensures a plasma membrane localization, and largely traffics between the nucleus and the cytoplasm. Ran regulates nucleo-cytoplasmic transport of molecules through the nuclear pore complex and controls cell cycle progression through the regulation of microtubule polymerization and mitotic spindle formation. The disruption of Ran expression has been linked to cancer at different levels - from cancer initiation to metastasis. In the present review, we discuss the contribution of Ran in the acquisition of three hallmarks of cancer, namely, proliferative signaling, resistance to apoptosis, and invasion/metastasis, and highlight its prognostic value in cancer patients. In addition, we discuss the use of this GTPase as a therapeutic target in cancer. | Authentic |
Text : Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Currently available therapies for hormone-refractory PCa are only marginally effective. Plumbagin (PLB), a natural naphthoquinone isolated from the traditional folk medicine Plumbago zeylanica, is known to selectively kill tumor cells. Nevertheless, antitumor mechanisms initiated by PLB in cancer cells have not been fully defined. MTT assay was used to evaluate the effect of PLB on the viability of cancer cells. Cell apoptosis and reactive oxygen species (ROS) production were determined by flow cytometry. Protein expression was detected by western blotting. In vivo anti-tumor effect was measured by using tumor xenoqraft model in nude mice. In the present study, we found that PLB decreases cancer cell growth and induces apoptosis in DU145 and PC-3 cells. In addition, by increasing intracellular ROS levels, PLB induced a lethal endoplasmic reticulum stress response in PCa cells. Importantly, blockage of ROS production significantly reversed PLB-induced ER stress activation and cell apoptosis. In vivo, we found that PLB inhibits the growth of PCa xenografts without exhibiting toxicity Treatment of mice bearing human PCa xenografts with PLB was also associated with induction of ER stress activation. Inducing ER stress by PLB thus discloses a previously unrecognized mechanism underlying the biological activity of PLB and provides an in-depth insight into the action of PLB in the treatment of hormone-refractory PCa. | Authentic |
Text : MicroRNAs are well-established players in post-transcriptional gene modulation. We aim to explore the role of microRNA-15a-5p (miR-15a-5p)/sex determining region Y-box 9 (Sox9)/nuclear factor-κB (NF-κB) axis in inflammation and apoptosis of murine nucleus pulposus cells (NPCs) in intervertebral disc degeneration (IVDD). Expression levels of miR-15a-5p and Sox9 in disc tissues from IVDD patients were determined. The IVDD mouse models were established by disc puncture, and the modeled mice were accordingly injected with miR-15a-5p antagomir and/or overexpressed Sox9 plasmid, or their negative controls. Then, the expression of miR-15a-5p, Sox9 and p-p65, pathological changes and the apoptosis of NPCs in IVDD mouse intervertebral disc tissues were measured. The NPCs were isolated and cultured, which were then transfected with miR-15a-5p inhibitor, overexpressed or silenced Sox9 plasmids, or the NCs. Next, the expression of miR-15a-5p and Sox9, apoptosis, proliferation and cell cycle distribution of NPCs, and the contents of inflammatory factors in the NPCs were evaluated. MiR-15a-5p expression was increased while Sox9 expression was reduced in intervertebral disc tissues from IVDD patients and mice. Mouse NPCs were successfully isolated. The down-regulated miR-15a-5p could elevate Sox9 to activate p-p65 expression, suppress NPC apoptosis and inflammatory factor contents, promote proliferation of NPCs, and arrest the NPCs at S and G2/M phases. However, these effects could be reversed by silencing Sox9. Reduction of miR-15a-5p elevated Sox9 to inhibit the inflammatory response and apoptosis of NPCs in IVDD mice through the NF-κB pathway. This study may be helpful for IVDD treatment. | Counterfeit |
Text : Recently, sphingolipid derivatives, such as ceramide and sphingosine‑1‑phosphate (S1P), have emerged as key modulators in apoptotic cell death and cell proliferation. This study aimed to clarify the underlying signaling pathways of ceramide and S1P involved in breast cancer cell proliferation. Ceramide acyl chain length is determined by six mammalian ceramide synthases (CerS). We overexpressed CerS1 to 6 in MCF‑7 cells to examine whether ceramide signaling propagation varies as a function of acyl chain length. Among the six CerS, only CerS6 overexpression reduced phosphorylation of Akt, S6 kinase (S6K), and extracellular signal‑regulated kinases (ERK) as shown by western blotting. In addition, CerS6 overexpression reduced MCF‑7 cell proliferation. This effect was partially reversed by co‑treatment with MHY1485, an activator of mammalian target of rapamycin (mTOR), demonstrating an important role for the mTOR pathway in the CerS6‑mediated decrease in MCF‑7 cell proliferation. ERK inhibition, but not Akt inhibition, along with mTOR inhibition synergistically reduced MCF‑7 cell proliferation as measured by MTT assay. Notably, the expression of CerS6 and S1P receptor 2 (S1PR2), or CerS6 and sphingosine kinase 1 (SphK1), were negatively correlated according to the invasive breast carcinoma patient cohort in The Cancer Genome Atlas database. In addition, both SphK1 overexpression and S1P addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. Moreover, mTOR activity can be regulated by the balance between S1P and C16‑ceramide, which is generated by CerS6. | Authentic |
Text : Osteoarthritis (OA) is a degenerative disease characterized by deterioration of articular cartilage. The aim of this study was to identify and characterize the expression of microRNA-125b-5p (miR-125b-5p) in normal and OA synovial cells, and to determine its role in OA pathogenesis. First, the levels of miR-125b-5p and synoviolin 1 (SYVN1) were detected among normal, mild OA and severe OA groups with the use of quantitative PCR. Computational analysis was used to search for the target of the miR-125b-5p, and luciferase reporter assay system was used to validate SYVN1 as the target gene of miR-125b-5p. Then the SYVN1 expression level of cells transfected with miR-125b-5p mimics or inhibitors was estimated using quantitative PCR and western blotting. Finally, MTT assay was employed to estimate the effect of miR-125b-5p on apoptosis. We enrolled 36 participants consisting of 12 normal control, 12 mild OA and 12 severe OA, furthermore, we performed quantitative PCR to detect the levels of miR-125b-5p and SYVN1 among those groups, and found that miR-125b-5p was expressed at highest level in severe OA compared with normal control and mild OA groups, while SYVN1 was expressed at the lowest level in severe OA. Additionally, we identified that SYVN1 is a target of miR-125b-5p by using computational analysis and luciferase assay. Transfection with miR-125b-5p mimic or inhibitor was employed to investigate the effect of miR-125b-5p on expression of SYVN1 in synovial cells, and synovial cell viability and apoptosis, and the results showed that miR-125b-5p mimics significant decreased the expression of SYVN1, a substantially promoted apoptosis of synovial cells, while miR-125b-5p inhibitors remarkably increased the level of SYVN1, and substantially suppressed apoptosis of synovial cells. The data suggested that miR-125b-5p promoted apoptosis of synovial cells through targeting SYVN1 gene, with important implication for validating miR-125b-5p as a potential target for OA therapy. | Authentic |
Text : Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease that could eventually result in right ventricular failure. Recently, the roles of microRNAs (miRNAs) in PAH have been highlighted. The present study aims to investigate the effects of miRNA (miR)-340-5p on PAH induced by acute pulmonary embolism (APE) and the underlying mechanisms. miR-340-5p was lowly expressed, whereas interleukin 1β (IL-1β) and IL-6 were highly expressed in plasma of APE-PAH patients as compared to normal human plasma. Subsequently, IL-1β and IL-6 were confirmed to be two target genes of miR-340-5p using a dual-luciferase reporter gene assay. By conducting overexpression and rescue experiments, overexpression of miR-340-5p was evidenced to inhibit proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and inflammation via reducing IL-1β and IL-6 levels. Meanwhile, miR-340-5p led to the blocked nuclear factor κB (NF-κB) pathway with reduced NF-κB p65, matrix metalloproteinase 2 (MMP2), and MMP9 expression in PASMCs. Finally, the ameliorative effect of miR-340-5p on pathological lesions was further verified in rat models of APE-PAH. Altogether, overexpressed miR-340-5p inhibited the inflammatory response, proliferation, and migration of PASMCs by downregulating IL-1β and IL-6, thereby suppressing the progression of APE-PAH. miR-340-5p therefore holds promise as an anti-inflammatory therapeutic target. | Counterfeit |
Text : MicroRNAs (miRNAs) are important gene regulators that play key roles in tumor genesis. In this study, we investigate the role of miR-148a in the development of papillary thyroid cancer (PTC). Data from the cancer genome atlas (TCGA) indicate that miR-148a is downregulated in PTC tissues; we also find that miR-148a is downregulated in tissue samples from PTC patients and PTC cell lines. Overexpression of miR-148a significantly suppresses PTC cell proliferation, migration and invasiveness in vitro, and inhibits tumor growth in vivo as well. We have identified the cyclin-dependent kinase 8 (CDK8) gene as a direct target of miR-148a using the online software packages TargetScan and miRanda. Overexpression of miR-148a significantly represses CDK8 expression by directly targeting the 3'-untranslated region (3'-UTR) of the CDK8 gene in PTC tissues and cell lines; overexpression of CDK8 reverses the inhibitory effects of miR-148a on PTC cell growth, migration and invasiveness. Taken together, our results indicate that miR-148a functions as a tumor suppressor in PTC by repressing CDK8 expression. | Authentic |
Text : Pancreatic cancer is one of the most aggressive cancers. Preclinical and clinical data indicate that Notch 1 ligand jagged1 (JAG1) plays a pro-oncogenic role in several malignant cancers. As yet, however, the role of JAG1 in pancreatic cancer is poorly understood. The objective of the present study was to investigate JAG1 as a therapeutic target in human pancreatic cancer. Expression levels of Notch signaling molecules were assessed using GEO datasets and Western blot analysis, respectively. Anti-tumor effects following JAG1 silencing were evaluated using in vitro and in vivo assays. Prognostic implications were assessed using GEO datasets. Using GEO datasets and Western blot analysis we detected significantly higher JAG1 mRNA and protein expression levels in pancreatic cancer compared to normal pancreatic tissues. JAG1 silencing significantly restrained the growth, migration and invasion of pancreatic cancer cells through the induction of apoptosis and blockade of various kinases independent of the Notch1 pathway. Combined JAG1 silencing and gemcitabine treatment showed synergistic anti-viability effects in human pancreatic cancer cells. JAG1 silencing also resulted in significant anti-cancer effects in vivo and high JAG1 expression was found to be associated with an adverse prognosis in pancreatic cancer patients. From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer. | Authentic |
Text : Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures contained data that bore striking similarities to data published in other papers; notably, the western blot data shown in Fig. 6 appeared to have been presented in other studies, notably in Fig. 7B of another paper published around the same time and written by different authors based at different research institutions [Li P, Zhang Z, Zhang F, Zhou H and Sun W: Effects of 3‑tetrazolyl methyl‑3‑hydroxy‑oxindole hybrid (THOH) on cell proliferation, apoptosis, and G2/M cell cycle arrest occurs by targeting platelet‑derived growth factor D (PDGF‑D) and the MEK/ERK signaling pathway in human lung cell lines SK‑LU‑1, A549, and A‑427. Med Sci Monit 24: 4547‑4554, 2018]. Furthermore, cellular images featured in Fig. 2A and B of the above paper appeared in Fig. 2 of the following paper, albeit the data were presented in a different field of view: Yu L, Zhou G‑Q and Li D‑C: MiR‑136 triggers apoptosis in human gastric cancer cells by targeting AEG‑1 and BCL2. Eur Rev Med Pharmacol Sci 22: 7251‑7256, 2018. After having conducted an independent investigation in the Editorial Office, the Editor of International Journal of Molecular Medicine has determined that this article should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published on International Journal of Molecular Medicine 41, 3485-3492, 2018; DOI: 10.3892/ijmm.2018.3531]. | Authentic |
Text : Checkpoint kinase 2 gene (CHEK2) is an important mediator of the DNA damage response pathway. Single nucleotide polymorphisms (SNPs) have been shown to influence the developing risk and clinical characteristics in various types of human malignancies. The values of CHEK2 SNPs in HBV-related hepatocellular carcinoma patients (HCC) were unknown and discussed here. The expression and prognostic prediction role of CHEK2 were searched and analyzed in HBV-related HCC patients by GEO database. SNPs in CHEK2 were genotyped by SNP selection tools, and further assessed their associations with clinical outcomes of 339 HBV-related HCC patients. Patients with a higher CHEK2 gene expression predicted a worse relapse free survival (RFS). Moreover, those with a variant alleles CC/TT of SNPs rs1547014 and rs738722 had a significantly better prognosis when compared to the patients with CT genotype (P<0.015 for rs1547014, P=0.001 for rs738722), and CC/TT genotype combined with AFP≤400 ng/ml also predicted the best prognosis in HBV-related HCC patients. In stratified analysis, the protective effect of rs1547014 and rs738722 CC/TT genotype was more evident in patients with adverse strata, comparing the patients with favorable strata. CHEK2 SNPs rs1547014 and rs738722 probably be potential prognostic bio-markers in HBV-related HCC patients. | Authentic |
Text : Mesenchymal stem cells (MSCs) are pluripotent mesenchymal cells present in various adult tissues. MSCs secrete exosomes as regulators of the tumor niche, with involvement in tumorigenesis and metastasis. The regulatory role of microRNAs (miRs or miRNAs) in MSCs via targeting cyclin E1 (CCNE1) or cyclin E2 (CCNE2) has been extensively reported. Since exosomes are considered as protective and enriched sources of shuttle miRNAs, we hypothesized that exosomal transfer of miR-144 from bone marrow-derived MSCs (BMMSCs) would affect the development of non-small cell lung cancer (NSCLC) cells by targeting CCNE1 and CCNE2. We first quantified the levels of miR-144, CCNE1, and CCNE2 in NSCLC tissues and cell lines and then undertook gain- and loss-of-function studies of miR-144, CCNE1, and CCNE2 to investigate their roles in the biological characteristics of NSCLC in vitro. NSCLC cells (A549) were exposed to exosomes derived from MSCs, and cell proliferation and colony formation rate were determined using in vitro assays. Finally, effects of BMMSC-derived exosomal miR-144 on tumor development were studied in vivo. In NSCLC tissues and cell lines, miR-144 was expressed poorly and CCNE1 and CCNE2 were expressed highly. Artificially elevating miR-144 inhibited cell proliferation, colony formation, and the number of S phase-arrested cells in NSCLC by downregulating CCNE1 and CCNE2. Additionally, BMMSC-derived exosomal miR-144 led to restrained NSCLC cell proliferation and colony formation. These inhibitory effects of BMMSC-derived exosomes carrying miR-144 on NSCLC were confirmed by experiments in vivo. Collectively, these findings revealed inhibitory effects of BMMSC-derived exosomal miR-144 on NSCLC progression, which were mediated by downregulation of CCNE1 and CCNE2. | Counterfeit |
Text : Breast cancer is the leading cancer in women, which accounts for millions of deaths worldwide. Early and accurate detection, prognosis, cure, and prevention of breast cancer is a major challenge to society. Hence, a precise and reliable system is vital for the classification of cancerous sequences. Machine learning classifiers contribute much to the process of early prediction and diagnosis of cancer. In this paper, a comparative study of four machine learning classifiers such as random forest, decision tree, AdaBoost, and gradient boosting is implemented for the classification of a benign and malignant tumor. To derive the most efficient machine learning model, NCBI datasets are utilized. Performance evaluation is conducted, and all four classifiers are compared based on the results. The aim of the work is to derive the most efficient machine-learning model for the diagnosis of breast cancer. It was observed that gradient boosting outperformed all other models and achieved a classification accuracy of 95.82%. | Authentic |
Text : microRNA (miRNA) plays critical role in HCC initiation and development, many miRNAs have been reported to regulate HCC progression. In this study, we studied the role of miR-1299 in cell proliferation of HCC. We found miR-1299 was significantly downregulated in HCC cells and tissues. miR-1299 overexpression inhibited cell proliferation and arrested cell cycle in G0/G1 phase analyzed by MTT assay, soft agar assay, BrdU cell proliferation assay and cell cycle assay, while miR-1299 knockdown promoted cell proliferation and accelerated G1/S transition. Further analysis suggested the key regulator of G1/S transition, cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited CDK6 expression and bound to the 3'UTR of CDK6. When double knockdown of miR-1299 and CDK6 promoted cell proliferation copied the phenotype caused by miR-1299 overexpression, suggesting miR-1299 inhibits cell proliferation by targeting CDK6. In summary, our data revealed miR-1299 inhibits cell proliferation, and might be a target for HCC therapy. | Authentic |
Text : microRNAs (miRNA) in extracellular vesicles (EVs) have been investigated as potential biomarkers for pancreatic ductal adenocarcinoma (PDAC). However, a mixed population of EVs is often obtained using conventional exosome isolation methods for biomarker development. EVs are derived from different cellular processes and present in various sizes, therefore miRNA expression among them is undoubtedly different. We developed a simple protocol utilizing sequential filtration and ultracentrifugation to separate PDAC EVs into three groups, one with an average diameter of more than 220 nm, named operational 3 (OP3); one with average diameters between 100-220 nm, named operational 2 (OP2); and another with average diameters around 100 nm, named operational 1 (OP1)). EVs were isolated from conditioned cell culture media and plasma of human PDAC xenograft mice and early stage PDAC patients, and verified by nanoparticle tracking, western blot, and electronic microscopy. We demonstrate that exosome specific markers are only enriched in the OP1 group. qRT-PCR analysis of miRNA expression in EVs from PDAC cells revealed that expression of miR-196a and miR-1246, two previously identified miRNAs highly enriched in PDAC cell-derived exosomes, is significantly elevated in the OP1 group relative to the other EV groups. This was confirmed using plasma EVs from PDAC xenograft mice and patients with localized PDAC. Our results indicate that OP1 can be utilized for the identification of circulating EV miRNA signatures as potential biomarkers for PDAC. | Authentic |
Text : The present study aimed to investigate the role of leptin in the growth of breast cancer. In the present study, expression of leptin in tumor tissues and adjacent tissues was detected by reverse transcription-quantitative polymerase chain reaction. Serum leptin in patients with breast cancer and normal healthy controls was detected by ELISA. Different concentrations of leptin were used to treat breast cancer cells, and cell proliferation was detected by cell proliferation assay. Interactions between leptin and Wnt/β-catenin were evaluated by western blotting. It was demonstrated that expression of leptin mRNA was significantly higher in tumor tissues than in adjacent tissues in 43 out of 48 patients. Serum level of leptin was significantly higher in patients with breast cancer than in normal controls. Leptin promoted the proliferation of breast cancer cells in a dose-dependent manner. Leptin significantly increased the expression level of β-catenin in breast cancer cells. Treatment with Wnt inhibitor reduced the enhancing effects of leptin on proliferation of breast cancer cells. The results of the present study therefore indicate that leptin may promote the growth of breast cancer by upregulating the Wnt/β-catenin pathway. | Authentic |
Text : The aim of present study was to develop the efficient targeting of Concanavalin-A conjugated nanotransfersomal gel to bind directly to melanocytes gel layer against UVB induced skin carcinoma. Carbopol loaded nanotransfersomal gel have prepared by modified rotary evaporation sonication technique & conjugated synthesized by carbodiimide method and they were characterized the morphology, zeta potential, penetration and cell viability. In vitro release studies & skin permeation have determined using Franz diffusion cell and confocal laser scanning microscope (CLSM). The conjugated formulation showed vesicles size, polydispersity index, zeta potential and % conjugation efficiency of 179.0 ± 0.32 nm, 0.197 ± 0.07, 35.1 ± 0.21 mV and 89.73 ± 1.29% respectively. The surface morphology was confirmed by transmission electron microscopy (TEM) and FTIR to make sure the compatibility among its ingredients. Con-A conjugated nanotransfersomal gel showed toxicity on melanoma (A375) in a concentration range of 0.4-2.0 mg/mL, but less toxicity toward HaCaT cells. The MTT assay has analyzed against two different cell lines, to determine their anti-cancer potentials and their targeting ability. Conjugated formulation were found to decrease the cell viability, higher skin targeting efficacy in in-vitro & in-vivo. Concanavalin conjugated nanotransfersomal gel of apigenin promise an efficient and economic approach for the skin cancer. | Authentic |
Text : Since the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis. A GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis. miR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p. The plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients. | Authentic |
Text : The roles of microRNAs (miRNAs) have been widely exploited in cancer. MiRNAs have become a potential breakthrough in cancer diagnosis and treatment. Here, the regulatory mechanism of microRNA-488 (miR-488) was investigated in ovarian cancer (OC). The expression levels of miR-488 and CCNG1 (Cyclin G1) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot assays. Transwell assay and epithelial-mesenchymal transition (EMT) markers were used to clarify the effect of miR-488 on cell metastasis. The dual-luciferase reporter assay was used to verify the relation between miR-488 and CCNG1. The expression of miR-488 was reduced in OC, which was associated with poor clinical outcomes and prognosis in OC patients. MiR-488 inhibited cell metastasis in OC by blocking EMT and promoting tumor suppressor p53 expression. In addition, CCNG1 was confirmed as a direct target of miR-488. Upregulation of CCNG1 impaired the inhibitory effect of miR-488 in OC. MiR-488 serves as a tumor inhibitor in OC by suppressing cell metastasis, indicating that miR-488 has a great potential in the diagnosis and treatment of OC. | Authentic |
Text : Metabolic reprogramming of cancer cells results in a high production of acidic substances that must be extruded to maintain tumor-cell viability. The voltage-gated proton channel (Hv1) mediates highly selective effluxes of hydronium-ion (H+ ) that prevent deleterious cytoplasmic acidification. In the work described here, we demonstrated for the first time that the amino-terminal-truncated isoform of Hv1 is more highly expressed in tumorigenic breast-cancer-cell lines than in nontumorigenic breast cells. With respect to Hv1 function, we observed that pharmacologic inhibition of that channel, mediated by the specific blocker 5-chloro-2-guanidinobenzimidazole, produced a drop in intracellular pH and a decrease in cell viability, both in monolayer and in three-dimensional cultures, and adversely affected the cell-cycle in tumorigenic breast cells without altering the cycling of nontumorigenic cells. In conclusion, our results demonstrated that the Hv1 channel could be a potential tool both as a biomarker and as a therapeutic target in breast-cancer disease. | Authentic |
Text : Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti-tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three-dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5-FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress-related molecules were highly expressed in ALG bead-encapsulated HCC cells compared with two-dimensional-cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration. | Authentic |
Text : Background：Aloe-emodin, an anthraquinone present in aloe latex, has been shown to have anti-proliferative properties in cervical cancer disease, all cases of which are almost caused by human papillomavirus (HPV), with the products of E6/E7. It is suggested that aloe-emodin may play an important role in HPV-induced cervical cancer cells. Methods：Hela and SiHa cells were treated with various concentrations of aloe-emodin. MTT assay and flow cytometry were used to identify the cell growth and apoptosis. The expressions of HPV E6, E7 and GLUT1 (glucose transporter-1) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB). The glucose uptake, lactate production and ATP production in HeLa and SiHa cells were also investigated. Result：The results indicate that aloe-emodin promoted the apoptosis of HeLa and SiHa cells and decreased the expressions of HPV-related protein E6 and E7. Furthermore, aloe-emodin inhibited glucose metabolism by reducing GLUT1 expression. Overexpression of GLUT1 significantly weakened the apoptosis induced by aloe-emodin in HeLa cells. Conclusion：In this study, we found that aloe-emodin induce apoptosis of cervical cancer cells, which was associated with HPV E6 and E7 and glucose metabolism. | Authentic |
Text : Breast cancer is the most common neoplasm diagnosed in women around the world. Checkpoint inhibitors, targeting the programmed death receptor-1 or ligand-1 (PD-1/PD-L1) axis, have dramatically changed the outcome of cancer treatment. These therapies have been recently considered as alternatives for treatment of breast cancers, in particular those with the triple-negative phenotype (TNBC). A further understanding of the regulatory mechanisms of PD-L1 expression is required to increase the benefit of PD-L1/PD-1 checkpoint immunotherapy in breast cancer patients. In this review, we will compile the most recent studies evaluating PD-1/PD-L1 checkpoint inhibitors in breast cancer. We review factors that determine the therapeutic success of PD-1/PD-L1 immunotherapies in this pathology. In particular, we focus on pathways that interconnect the epithelial-mesenchymal transition (EMT) with regulation of PD-L1 expression. We also discuss the relationship between cellular metabolic pathways and PD-L1 expression that are involved in the promotion of resistance in TNBC. | Authentic |
Text : As a treasure among Chinese national musical instruments, guzheng is an important part of traditional Chinese music. As the art of national music goes to the world, the art of guzheng has been widely promoted. As the best form to carry forward the art of guzheng, the teaching of guzheng majors in colleges is significant in teaching and continuously improves guzheng art accomplishment. Oral teaching and step-by-step music theory and technique teaching are typical ways of teaching musical instrument performance in colleges. However, under big data, Chinese education is undergoing a profound change, and the combination of big data and education has become a new contemporary education method. This work studies the guzheng professional education in colleges under big data. First, this work aims at the existing outstanding issues of guzheng teaching in colleges and studies the challenges and optimization paths of guzheng professional education in colleges under big data. Second, this work proposes a multiscale residual attention fusion network (MSRAFNET) to evaluate the teaching quality of guzheng majors in colleges in the era of big data. The feature extraction of the network model is mainly completed by the residual module, which is composed of several multiscale residual learning units. Adding an attention mechanism to the multiscale residual learning unit can enhance the feature extraction of key information by the network and reduce the interference of redundant information, which is more conducive to the learning of data features. It adopts the design of GAP and Dropout to reduce spatial parameters in network training, and the effect of antioverfitting is better. Third, this work systematically evaluates the optimization path of Guzheng education and MSRAFNET, and the systematic experiments verify the superiority of the designed method. | Counterfeit |
Text : Xantholipin is a polycyclic xanthone antibiotic that exhibits potent cytotoxic and antibacterial activity. In this study, a new xanthone-type antibiotic, xantholipin B (1), was isolated for the first time along with its known derivative, xantholipin (2), from strain WJN-1, an aminotransferase inactivation mutant of the streptonigrin-producer Streptomyces flocculus CGMCC 4.1223. The structure of 1 was established based on spectroscopic analysis and supports the previously proposed biosynthetic pathway as a key intermediate of 2. Moreover, 1 showed 3- to 10-fold greater cytotoxicity than 2 against a select panel of human cancer cell lines. In addition, 1 demonstrated powerful antimicrobial activity against both Gram-positive bacteria and fungi. Importantly, both 1 and 2 inhibited the methicillin-resistant strain Staphylococcus aureus Mu50, with the MIC value of 0.025 μg ml-1. The new structural features of 1 enrich the structural diversity of xantholipin family compounds and shed new light on the structure-activity relationship of 1 as a promising antitumor drug candidate. | Counterfeit |
Text : Accumulating evidence has indicated that long noncoding RNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1, which are responsible for human gastric cancer (GC), are still largely unknown. Here, we observed that NEAT1 and STAT3 expressions were significantly upregulated in human GC cells including BGC823, SGC-7901, AGS, MGC803, and MKN28 cells compared with normal gastric epithelial cells GES-1, while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration, and invasion of GC cells. Conversely, overexpression of NEAT1 exhibited an increased ability of GC progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual luciferase reporter assays, RIP assays, and RNA pull-down tests validated the negative binding correlation between NEAT1 and miR-506. In addition, it was found that miR-506 can modulate the expression of NEAT1 in vitro. STAT3 was predicted as a messenger RNA (mRNA) target of miR-506, and miR-506 mimics can suppress STAT3 mRNA expression. Subsequently, it was observed that downregulation of NEAT1 can restrain GC development by decreasing STAT3, which can be reversed by miR-506 inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be recognized as a competing endogenous RNA to modulate STAT3 by sponging miR-506 in GC. In conclusion, we implied that NEAT1 can serve as an important biomarker in GC diagnosis and treatment. | Authentic |
Text : Chemo-photothermal therapy, which exhibits synergistic effects, is more effective than either of the treatments administered alone because of its superior ability to target and destroy cancer cells. An anti-cancer compound (doxorubicin, DOX) was embedded in silica-carbon hollow spheres (SCHSs) using heat and vacuum to integrate multi-therapeutic effects onto one platform and subsequently improve the anti-cancer efficacy. SCHSs were synthesized via a surface activation method and its highly porous surface enhanced the loading content of the desired drug. SCHSs are an infrared photothermal material that can destroy targeted cells by heating under near-infrared (NIR) laser illumination at 808 nm. NIR laser illumination also enhances DOX release from SCHSs to increase the anti-cancer efficiency of DOX-loaded SCHSs (DOX-SCHSs) in both two-dimensional and three-dimensional multicellular tumor spheroid cultures. SCHSs exhibited high heat-generating ability and pH-responsive drug delivery. In conclusion, this study demonstrated that DOX-SCHSs represent a potential tool for chemo-photothermal therapy due to its photothermal effects. Thus, our findings imply that the high cancer cell killing efficiency of DOX-SCHSs induced by NIR illumination can be used for the treatment of tumors. | Authentic |
Text : Homeobox A10 (HOXA10) has been regarded to serve as an oncogene in head and neck squamous cell carcinoma (HNSCC). This study was intended to explore the interaction among the long intergenic noncoding RNA 00461 (LINC00461), microRNA (miR)-195, and HOXA10, and to investigate its role in epithelial-mesenchymal transition (EMT) and chemoresistance in HNSCC. The effects of LINC00461, miR-195, and HOXA10 on the EMT and chemoresistance of HNSCC cells were analyzed by comprehensive analysis of gain- and loss-of-function techniques. The intimate relationships among LINC00461, miR-195, and HOXA10 were investigated by several procedures such as RNA-binding protein immunoprecipitation, RNA pull-down, and dual-luciferase reporter assays. A xenotransplantation tumor model in nude mice was established for the assessment of the tumorigenic ability of the cells in vivo. Our findings indicated that LINC00461 was highly expressed in HNSCC and its overexpression induced EMT and precipitated the chemoresistance of HNSCC cells to cisplatin. The LINC00461 could bind to miR-195 while miR-195 targeted HOXA10 independently. Moreover, LINC00461 impaired miR-195-mediated inhibition of HOXA10 to induce EMT and increase the chemoresistance in HNSCC. Tumor weight and volume were reduced by lentivirus-mediated elevation of miR-195 by inhibition of HOXA10, which could be annulled by LINC00461 overexpression. LINC00461 downregulates the expression of miR-195 to subsequently upregulate the expression of HOXA10, thereby promoting EMT and enhancing chemoresistance in HNSCC. | Authentic |
Text : Herein we hypothesized that DPP10-AS1 could affect the development of colon cancer via the interaction with miR-127-3p and adenylate cyclase 1 (ADCY1). After sorting of CD133 positive cells, sphere formation, colony formation, proliferation, invasion, migration, and apoptosis were detected to explore the involvement of DPP10-AS1 and miR-127-3p in the colon cancer stem cell (CCSC) properties through gain- and loss-of function approaches. Furthermore, tumor xenograft in nude mice was conducted to investigate the effect of DPP10-AS1 and miR-127-3p on tumor growth in vivo. Poorly expressed DPP10-AS1 and ADCY1, while highly expressed miR-127-3p were found in CCSCs. Low expression of DPP10-AS1 was correlated with TNM stage, lymphatic node metastasis, and tumor differentiation. Upregulation of DPP10-AS1 increased ADCY1 protein expression, decreased the protein expression of CCSC-related factors, inhibited sphere formation, colony formation, proliferation, invasion and migration, and accelerated apoptosis of HT-29 and SW480 cells by suppressing the expression of miR-127-3p. Further, the above in vitro findings were also confirmed by in vivo assays. Taken together, this study demonstrates that DPP10-AS1 inhibits CCSC proliferation by regulating miR-127-3p and ADCY1, providing fresh insight into a promising novel treatment strategy for colon cancer. | Counterfeit |
Text : Epithelial ovarian cancer (EOC) patients frequently suffer from thrombocytosis, which leads to a poor prognosis. However, the mechanism underlying platelet regulation of biological behavior in EOC remains unclear. The associations between clinicopathological characteristics and thrombocytosis in 171 EOC patients were studied, preoperative thrombocytosis was significantly associated with the stage, metastasis scope, level of preoperative CA125 and overall survival. When SKOV3 cells were cocultured with platelet microparticles (PMPs), the expression of molecules associated with epithelial-mesenchymal transition (EMT) was increased. The proliferation and migration of SKOV3 cells were also enhanced. Based on the miRNA microarray of the PMPs derived between thrombin-stimulating and apoptotic platelets, we demonstrated that over-expression or complete knockdown of miR-939 in the SKOV3 cells strengthened or weakened EMT. Secretory phospholipase A2 type IIA (sPLA2-IIa) has been shown to mediate PMPs intake by SKOV3 cells. The knockdown of sPLA2-IIa in SKOV3 cells verified that PMPs were involved in crosstalk during the regulation of cancer cells by transferring miRNA. This study revealed an important role for PMPs in the crosstalk of platelets and cancer cells through miR-939 shedding mediated by sPLA2-IIa, which enables EOC to undergo EMT and enhances cancer progression. Our findings pave the way for developing a novel therapeutic strategy for EOC targets such as PMPs, miR-939 or sPLA2-IIa. | Authentic |
Text : Prostate cancer stem-like cells (PCSCs) likely participate in tumor progression and recurrence and demonstrate resistance to chemotherapy. The Notch pathway plays a role in the maintenance of the stemness in PCSCs. This study aimed to investigate the efficacy of Notch signaling inhibition as an adjuvant to docetaxel (DOX) in PCSCs. PCSCs derived from the PC-3 cell line were examined for Notch-1 expression. The effect of Notch inhibition on response to DOX was evaluated in PCSCs in vitro and in murine models using a γ-secretase inhibitor (GSI), PF-03084014. Impacts on cell proliferation, apoptosis, cell cycle, and sphere formation were evaluated. PC-3 PCSCs expressed elevated Notch-1 mRNA compared with PC-3 parental cells. The combination of GSI with DOX promoted DOX-induced cell growth inhibition, apoptosis, cell cycle arrest, and sphere formation in PCSCs. In nude mice bearing PC-3 PCSC-derived tumors, the combination of GSI and DOX reduced the tumor growth, which was associated with the decreased Notch-1 expression in tumor tissues. These results reveal that inhibition of the Notch pathway enhances the anti-tumor effect of DOX in PC-3 PCSCs, and suggest that Notch inhibition may have clinical benefits in targeting PCSCs. | Authentic |
Text : Non-small cell lung cancer (NSCLC) is the second most prevalent cause of cancer-related fatality. Long non-coding RNAs (lncRNAs) have been observed to exercise functions in NSCLC. Here, the current study aimed to explore the potential mechanism of lncRNA MBNL1-AS1 in NSCLC. Microarray analysis was performed to screen the differentially expressed lncRNA associated with NSCLC and its potential mechanism. The lncRNA MBNL1-AS1 expression was quantified in 56 paired NSCLC and adjacent normal tissue samples. In an attempt to outline the function of lncRNA MBNL1-AS1 in NSCLC and to identify the interaction among lncRNA MBNL1-AS1, microRNA-301b-3p (miR-301b-3p) and TGFBR2, ectopic expression, depletion, and reporter assay experiments were conducted to detect CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. Initially, the intersection among lncRNA MBNL1-AS1, miR-301b-3p, and TGFBR2 was observed in NSCLC. While a poor expression of lncRNA MBNL1-AS1 and TGFBR2, along with a high expression of miR-301b-3p was observed in NSCLC tissues. A demonstration of lncRNA MBNL1-AS1 restoration significantly decreased CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 functioned as a sponge of miR-301b-3p, which inverted the inhibitory role of lncRNA MBNL1-AS1 in CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 positively regulated TGFBR2 which was a target gene of miR-301b-3p. At last, upregulated lncRNA MBNL1-AS1 or depleted miR-301b-3p suppressed the xenograft tumor formation in vivo. Collectively, the present study suggests an inhibitory role of lncRNA MBNL1-AS1 in CSC drug resistance of NSCLC by upregulating miR-301b-3p-targeted TGFBR2. | Authentic |
Text : The vital role of long noncoding RNAs (lncRNAs) in tumor progression have been identified in numerous studies. In this research, lncRNA ROR1-AS1 was explored to verify its function during the development of lung adenocarcinoma (LAC). Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure ROR1-AS1 expression of LAC tissues. Function assays including wound healing assay and transwell assay were conducted to detect the effect of knockdown of ROR1-AS1 on the metastasis of LAC, and luciferase assays and RNA immunoprecipitation assay (RIP) were also performed to explore the underlying mechanism. ROR1-AS1 expression level was significantly higher in LAC samples compared with that in adjacent tissues, which was associated with patients' prognosis. Knockdown of ROR1-AS1 inhibited cell migration and cell invasion of LAC cells via suppressing epithelial-mesenchymal transition (EMT) process. Furthermore, it was discovered that ROR1-AS1 acted as a competing endogenous RNA via sponging miR-375 in LAC. These results suggested that ROR1-AS1 could act as a sponge for miR-375 and promo//e cell migration and invasion through suppressing the process of EMT in LAC, which may offer a potential therapeutic target in LAC. | Counterfeit |
Text : Human skin melanoma is one of the most aggressive and difficult to treat human malignancies, with an increasing incidence over the years. While the resection of the early diagnosed primary tumor remains the best clinical approach, advanced/metastatic melanoma still remains with a poor prognosis. Indeed, although enormous progress in the therapeutic treatment of human tumors has been made in recent years, patients affected by metastatic melanoma are still poorly affected by these clinical advances. Therefore, new valuable therapeutic approaches are urgently needed, to design and define effective treatments to consistently increase the overall survival rate of patients affected by this malignancy. In this review we summarize the main signaling pathways studied to kill human skin melanoma, and introduce the ferroptotic cell death as a new pathway to be explored to eradicate this tumor. | Authentic |
Text : Cancer‑associated fibroblasts (CAFs) are known to be essential in cancer initiation and development. However, the role of CAFs in promoting ovarian cancer (OC) invasion remains to be fully elucidated. To address this in the present study, 49 clinical OC specimens were used to evaluate the roles of CAFs in promoting ovarian tumor migration and invasion and disease progression. It was found that the sushi repeat‑containing protein, X‑linked (SRPX) and hemicentin 1 (HMCN1) genes were significantly upregulated in CAFs from high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) samples, the two major histological types of OC with frequently poor patient survival rates. The short hairpin (sh)RNA‑mediated silencing of SRPX and HMCN1 in fibroblasts significantly suppressed the Transwell invasive activities of OC cells. Further experiments showed that SRPX and HMCN1 regulated the invasiveness of OC via the Ras homology family member A (RhoA) signaling pathway in fibroblasts. Therefore, the findings of the present study suggest that targeting the CAF genes, SRPX and HMCN1, can inhibit OC migration and invasion. These data highlight the importance of CAF‑OC crosstalk signaling in cancer invasion and demonstrate the potential for improved efficacy of OC treatment by targeting CAF‑SRPX/HMCN1. | Authentic |
Text : Professor Lorenz Poellinger (Karolinska Institute/Cancer Science Institute of Singapore) passed away in March 2016. Then hypoxic research field lost a noble and unique researcher when he died, since he had contributed very much to this field in a variety of aspects. We had been collaborating on a various research projects of genomic analyses of HIF-signaling pathway for a long time, and recently reported several interesting results with HIF-α genes (HIF1A, EPAS1 and HIF3A). Genomics/Genetics is a still growing field, with new technologies appearing often, and many groups have performed extensive genomic/genetic analyses. In this review, I thus focused on the genetics of HIF-α genes in human cancers. I deeply mourn Professor Poellinger's loss and dedicate this review to him. | Authentic |
Text : Recently, long noncoding RNAs (lncRNAs) have captured much attention for their important roles in human diseases. Deregulation of lncRNA taurine-upregulated gene 1 (TUG1) has been reported to regulate cancer progression in many cancer types. However, how TUG1 contributes to renal cell carcinoma (RCC) remains elusive; we were eager to resolve the questions. Tumor tissues and the matched adjacent normal tissues were collected from patients with RCC. Messenger RNA (mRNA) levels of TUG1, yes-associated protein (YAP), and microRNA (miR)-9 levels were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The regulation of YAP by TUG1 was investigated using Western blot analysis, RT-qPCR, and immunofluorescence. The oncogenic roles of TUG1 and YAP were studied using a cell proliferation assay and a wound healing assay. The interaction of TUG1-miR-9-YAP was analyzed in RCC cell lines. In the current study, we observed a positive correlation between TUG1 expression and YAP expression in RCC using the Gene Expression Omnibus database and tumor tissues collected from 58 patients with RCC. The TUG1 elevation enhanced YAP expression but did not alter the Hippo-signaling pathway activity or YAP protein distribution in cells. In addition, we found that TUG1 could bind to miR-9; therefore, TUG1 could positively control YAP expression via downregulation of miR-9 level. Furthermore, we observed that inhibition of cell proliferation and cell migration induced by TUG1 silencing could be reversed by overexpression of YAP in RCC cell lines. Our findings indicated a pivotal role of TUG1 in driving RCC progression via regulation of miR-9/YAP, suggesting a potential therapeutic targeting role of TUG1 in RCC. | Authentic |
Text : Breast cancer is the leading cancer in women, which accounts for millions of deaths worldwide. Early and accurate detection, prognosis, cure, and prevention of breast cancer is a major challenge to society. Hence, a precise and reliable system is vital for the classification of cancerous sequences. Machine learning classifiers contribute much to the process of early prediction and diagnosis of cancer. In this paper, a comparative study of four machine learning classifiers such as random forest, decision tree, AdaBoost, and gradient boosting is implemented for the classification of a benign and malignant tumor. To derive the most efficient machine learning model, NCBI datasets are utilized. Performance evaluation is conducted, and all four classifiers are compared based on the results. The aim of the work is to derive the most efficient machine-learning model for the diagnosis of breast cancer. It was observed that gradient boosting outperformed all other models and achieved a classification accuracy of 95.82%. | Authentic |
Text : This study explored Cisplatin resistance effect of microRNA-21 (miR-21) antisense oligonucleotide (AS-ODN) in human melanoma A375 cell. AS-ODN was transfected in melanoma A375 cells and Cisplatin-resistant cell line A375/CDDP, and divided into the AS-ODN, nonsense oligonucleotide (NS-ODN) and normal groups. Cell ultrastructure changes were observed through transmission electron microscope. MiR-21 AS-ODN could be tested cell growth effect in different time periods by trypan blue exclusion. MiR-21 mRNA expression change was detected by quantitative fluorescence PCR. Cell apoptosis, cycle distribution and miR-21 AS-ODN effect on proliferation and Cisplatin sensitivity were tested by flow cytometry, MTT assay, TUNEL, and Clonogenic assay. Cell apoptosis was observed after transfection 24 h with the AS-ODN group, while the NS-ODN and normal group cells had no apoptotic symptoms; Compared with the normal group, the AS-ODN group began to show obvious cell growth inhibition effect after transfection 24 h lasting 72 h (all P < 0.05), but the NS-ODN group had no significant difference (P > 0.05). miR-21 mRNA expression in the AS-ODN group was obviously decreased with rising apoptosis rate (all P < 0.05) and there was no significant difference in the NS-ODN group (P > 0.05). MiR-21 AS-ODN could remarkably increase A375 cell and A375/CDDP cell sensitivity to Cisplatin (P < 0.05), while A375 cell sensitivity to Cisplatin between the NS-ODN group and the normal group had no difference. MiR-21 AS-ODN decreased IC50 and increased Cisplatin sensitivity for A375 cells and A375/CDDP cells, which would be a new target of melanoma treatment. | Counterfeit |
Text : Pulsatilla chinensis is one of the 50 famous fundamental herbs used in traditional Chinese medicine. Saponins are the main components of P. chinensis. Although the anti-proliferative function of saponins has been established in plenty types of cancer, the role of saponins on tumor invasion and metastasis has not been reported, and the mechanisms of how saponins exert the anti-tumor functions are still poorly characterized. Here, we demonstrate that, in breast cancer (BC) cells, raddeanoside R13, a component of saponins extracted from P. chinensis, exhibits strong anti-proliferative and anti-metastasis ability, accompanied by cell cycle arrest, apoptosis, autophagy, and reversion of epithelial-mesenchymal transition (EMT). Raddeanoside R13 (R13) inhibits BC cell proliferation via the activation of G1/S checkpoint transitions, concomitant with a marked decrease of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. R13 induces BC cell apoptosis accompanied by the increased levels of cleaved PARP and caspase-3. R13 inhibits BC cell migration and invasion and regulates the expression of the markers of EMT, which plays a critical role in cancer cell migration and invasion. Moreover, R13 suppresses BC tumor growth and metastasis in nude mice. These data highlight the important role of R13 in BC cell proliferation and progression and suggest that R13 may be a useful drug for BC therapy. | Authentic |
Text : Trichomicin, a novel small-molecule compound isolated from the fungus Trichoderma harzianum and identified as new structure compound, exhibited antitumor activities in various human cancer cell lines and reversed drug resistance activity in the multidrug-resistant cancer cell line KBV. The underlying cellular and molecular mechanism was illuminated. Trichomicin can significantly induce cancer cell apoptosis and reduced IL-6 expression and phosphorylation of STAT3 were found in response to Trichomicin treatment. The blockade of IL-6 mediated JAK-STAT3 signaling pathway by Trichomicin was confirmed using reporter gene system. As a promising antitumor-activity compound, Trichomicin is presented in this study. | Counterfeit |
Text : Erectile dysfunction (ED) is a common sexual problem for men and the exploration of its treatment is still in mire demand. We aim to investigate the role of the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the pathogenesis of angiotensin II (Ang-II) induced ED. Male Sprague-Dawlay rats were treated with Ang-II and intracavernous pressure (ICP) was measured to confirm the occurrence of ED. The corpus cavernosum penises of rats were transfected with plasmids to overexpressed MyD88. Inflammatory and vascular parameters including myeloperoxidase (MPO), cyclooxygenase2 (COX2), endothelial nitric oxide synthase (eNOS), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), and cytokines in treated and untreated ED rats were measured. Flow cytometry was used to determine the apoptosis of endothelial cells of corpus cavernosum penises of rats. Ang-II-induced ED rats were found to contain upregulated TLR4, MyD88, MPO, and COX2, and downregulated eNOS. MyD88 overexpression deteriorates cavernous structural damage, reduces ICP and ICP/MAP values and reverses the therapeutic effect of anti-TLR4 antibodies in rats with Ang-II-induced ED. Moreover, overexpression of MyD88 further upregulated MPO and COX2, downregulated eNOS, promoted oxidative stress, inflammation, and cell apoptosis rate via positively regulating the TLR4/MyD88 signaling pathway, while anti-TLR4 antibodies downregulated MPO and COX2, upregulated eNOS, suppressed oxidative stress, inflammation, and cell apoptosis rate via inactivating the TLR4/MyD88 signaling pathway in the rat corpus cavernosum penises. Furthermore, MyD88 overexpression promotes oxidative stress and inflammation and reverses the effect of anti-TLR4 antibodies in the penis of ED rats. MyD88 overexpression deteriorates Ang-II-induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum rats. | Counterfeit |
Text : Carbon dots are nano-sized photoluminescence materials which have good biocompatibility and low cytotoxicity, while the previously synthesized carbon dots lack tumor targeting capability and therapy function so that it cannot achieve the purpose of diagnosis and treatment. Herein, a new kind of multi-functional carbon dots (GFCDs) is promising to be applied in tumor cells imaging and clinical targeted therapy. Gallic acid (GA) was used as the carbon resource and antitumor active molecule, folic acid (FA) was used as the nitrogen resource and tumor targeting molecule, and citric acid monohydrate (CA) was used as the auxiliary carbon source. Multi-functional GACDs were synthesized by a simple one-step microwave-assisted procedure and analyzed with UV - vis spectrophotometer, fourier transform infrared spectrometer, transmission electron microscopy and X-ray photoelectron spectrometer. Results show that the diameter of GFCDs is about 3 nm. And GFCDs are pale-yellow under natural light which turn blue under 360 nm UV lamp. Besides ester bond is the connecting mode between functional molecules. In addition, the results of in vitro cell imaging experiments and in vivo antitumor experiments demonstrate the targeting imaging and antitumor abilities towards Hela cells. The synthesis route and properties of GFCDs. | Authentic |
Text : The pre-mRNA splicing regulator serine-arginine protein kinase 1 (SRPK1), a member of the SR kinase family, plays an essential role in cancer development and various pathophysiological processes. However, its expression pattern and functions in renal cell carcinoma (RCC) remain unknown. Therefore, the aim of this study was to assess the role of SRPK1 in RCC. Our data showed that SRPK1 was significantly upregulated in human RCC tissues and cell lines. SRPK1 interference significantly inhibited the proliferation of RCC cells and inhibited tumor growth in vivo. In addition, SRPK1 interference also suppressed migration and invasion in RCC cells. A mechanistic study showed that SRPK1 interference inhibited the phosphorylation of PI3K and Akt in RCC cells. In conclusion, our findings suggest that SRPK1 interference inhibits the growth and invasion of RCC cells through suppressing the PI3K/Akt signaling pathway. Thus, SRPK1 might be a therapeutic target for the treatment of RCC. | Authentic |
Text : Pancreatic cancer (PC) is a devastating malignant disease with a poor prognosis. This study aimed to investigate the role of urothelial carcinoma associated 1 (UCA1) in the progression of PC. Our results revealed that long noncoding RNA (lncRNA) UCA1 was overexpressed in PC tissues compared with adjacent histologically normal tissues. A downregulated level of UCA1 was also detected in five human PC cell lines (SW1990, BxPC-3, MiaPaCa-2, PANC-1, and CAPAN-1) compared with normal pancreatic duct epithelial HPDE cells. The proliferation of PC cells was inhibited after UCA1 was suppressed by a lentiviral vector. The cell apoptosis rate was largely promoted by downregulating UCA1. Further research revealed that microRNA (miRNA)-135a is a direct target of UCA1. The expression of miR-135a was decreased in PC tissues and cell lines compared with control groups. In addition, the decreased level of miR-135a was elevated by adding miR-135a mimic in SW1990 cells transfected with lncRNA UCA1. Similarly, an upregulated level of miR-135a was downregulated by adding miR-135a inhibitor in SW1990 cells transfected with UCA1 siRNA. Luciferase activity assay further confirmed the targeting relationship between UCA1 and miR-135a. Moreover, miR-135a reversed the effect of UCA1 on cell apoptosis rate and cell viability in SW1990 cells. The migration and invasion capacities of PC cells were suppressed by UCA1. siRNA was then enhanced by the miR-135a inhibitor. In vivo, UCA1 siRNA effectively suppressed tumor growth and the expression of migration markers. Taken together, our research revealed that UCA1 works as an oncogene by targeting miR-135a. The UCA1-miR-135a pathway regulated the growth and metastasis of PC, providing new insight in the treatment of PC. | Authentic |
Text : Ovarian cancer (OC) is one of the most common malignant tumors in women. OC is associated with the activation of oncogenes, the inactivation of tumor suppressor genes, and the activation of abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role in OC tumorigenesis. Epigenetic processes do not change DNA sequences but regulate gene expression through DNA methylation, histone modification, and non-coding RNA. This review comprehensively considers the importance of epigenetics in OC, with a focus on microRNA and long non-coding RNA. These types of RNA are promising molecular markers and therapeutic targets that may support precision medicine in OC. DNA methylation inhibitors and histone deacetylase inhibitors may be useful for such targeting, with a possible novel approach combining these two therapies. Currently, the clinical application of such epigenetic approaches is limited by multiple obstacles, including the heterogeneity of OC, insufficient sample sizes in reported studies, and non-optimized methods for detecting potential tumor markers. Nonetheless, the application of epigenetic approaches to OC patient diagnosis, treatment, and prognosis is a promising area for future clinical investigation. | Authentic |
Text : Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells. Interleukins (ILs), pivotal cytokines that affect the function of immune cells, were co-expressed in CAR-T cells or combinatorially administered to enhance the therapeutic potential in clinical trials. In this review, we summarize the strategies exploited by ILs to improve the anti-cancer ability of CAR-T cells and the different impacts of different ILs on CAR-T cells. | Authentic |
Text : This network meta-analysis is adopted in order to compare the toxicity of different chemotherapy regimens in the treatment of advanced/metastatic pancreatic cancer (PC). Randomized controlled trials (RCTs) about different chemotherapy regimens for advanced/metastatic PC were included in this network meta-analysis using Cochrane Library and PubMed electronic databases. The network meta-analysis was performed to combine direct and indirect evidence in order to calculate the odd ratios (OR) and draw a surface under the cumulative ranking (SUCRA) curve. A total of 19 RCTs were enrolled in this network meta-analysis including 12 chemotherapy regimens (Gemcitabine, Gemcitabine + S-1 [tegafur], Gemcitabine + nab-paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX [oxaliplatin + irinotecan + fluorouracil + leucovorin], Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5-FU, S-1). The incidence of anemia of Gemcitabine + Capecitabine regimen was higher compared with Gemcitabine regimen, Gemcitabine + pemetrexed regimen exhibited the highest incidence rates of anemia and neutropenia; while Gemcitabine + S-1, Gemcitabine + Cisplatin and FOLFIRINOX regimens exhibited the highest incidence rates of neutropenia. However, S-1 regimen exhibited lower incidence rates of leukopenia and thrombocytopenia. Moreover, the incidence rates of nausea/vomiting and rash of Gemcitabine + S-1 regimen were higher compared with Gemcitabine regimen, while Gemcitabine + Cisplatin regimen had the highest incidence rate of nausea/vomiting. This study demonstrated that the hematologic toxicity of S-1 regimen was the lowest, while Gemcitabine regimen exhibited the lowest incidence rate of non-hematologic toxicity, providing guidance for the treatment of advanced/metastatic PC. | Authentic |
Text : Cytotoxic T cells expressing cell surface CD8 played a key role in anti-cancer immunotherapy, including kidney renal clear cell carcinoma (KIRC). Here we set out to comprehensively analyze and evaluate the significance of CD8+ T cell-related markers for patients with KIRC. We checked immune cell response in KIRC and identified cell type-specific markers and related pathways in the tumor-infiltrating CD8+ T (TIL-CD8T) cells. We used these markers to explore their prognostic signatures in TIL-CD8+ T by evaluating their prognostic efficacy and group differences at various levels. Through pan-cancer analysis, 12 of 63 up-regulated and 162 of 396 down-regulated genes in CD8+ T cells were found to be significantly correlated with the survival prognosis. Based on our highly integrated multi-platform analyses across multiple datasets, we constructed a 6-gene risk scoring model specific to TIL-CD8T. In this model, high TIL-CD8 sig score was corresponding to a higher incidence frequency of copy number variation and drug sensitivity to sorafenib. Moreover, the prognosis of patients with the same or similar immune checkpoint gene levels could be distinguished from each other by TIL-CD8 sig score. | Authentic |
Text : Our purpose was to assess the relationship between circ_0005276 and clinical features of epithelial ovarian cancer (EOC), and to illustrate the regulatory effect of circ_0005276 on migratory potential in EOC cells. EOC tissues and adjacent normal ones were collected from 49 EOC patients. Relative levels of circ_0005276 and ADAM9 in EOC tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ_0005276 and clinical features of EOC patients was analyzed. Moreover, migratory potentials of CAOV3 and SKOV3 cells affected by circ_0005276 were examined by transwell and wound healing assay. Regulatory effects of circ_0005276/ADAM9 feedback loop on the development of EOC were finally detected by Luciferase assay and rescue experiments. It was found that circ_0005276 was upregulated in EOC tissues and its level was positively linked to rates of lymphatic metastasis and distant metastasis in EOC patients. Survival analysis showed worse OS and DFS in EOC patients expressing a high level of circ_0005276 than those with a low level. Besides, knockdown of circ_0005276 attenuated migratory potentials in EOC cells. ADAM9 was verified to be the target gene binding circ_0005276, and its level was positively regulated by circ_0005276. Notably, circ_0005276 aggravated the development of EOC by targeting ADAM9. Circ_0005276 is highly expressed in EOC tissues, and its level is positively linked to metastasis. Serving as an unfavorable gene in the prognosis of EOC, circ_0005276 aggravates the development of EOC by upregulating ADAM9. | Authentic |
Text : Anastomotic leakage (AL) is a frequent complication after laparoscopic rectal cancer resection (LRCR). The main objective of the present study was to identify accurate indicators of AL after LRCR. A retrospective case-control study was performed of 185 patients who underwent laparoscopic surgery for rectal cancer between March 2012 and February 2017 at Beijing Friendship Hospital. Potential indicators of AL were examined via univariate and multivariate analyses. The performance of multivariate analysis was evaluated using receiver operating characteristic (ROC) curves. The overall AL rate was 17.84%. Multivariate analysis identified drainage smell (odds ratio [OR = 35.318, 95% confidence interval [CI] = 7.114 to 175.338) and peritonitis [OR = 17.475, 95% CI = 1.540 to 198.318) as independent indicators of AL. The area under the ROC curve was 0.720 (95% CI = 0.606 to 0.835). Drainage smell and peritonitis could be reliable and accurate indicators of AL after LRCR. | Authentic |
Text : Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer often occurs, so mutation testing from liquid biopsy is the method of choice as a minimally invasive approach that quickly provides information for additional therapeutic options. The purpose of this study was to assess the success rate and usefulness of EGFR testing from liquid biopsy at the Institute for Oncology and Radiology of Serbia (IORS). EGFR mutation testing was performed by real-time qPCR in 4750 tumor samples using the Cobas® EGFR Mutation Test v2. EGFR testing from 104 liquid biopsy samples was used to track the resistance on first-line EGFR-TKIs as well as for initial testing of 124 patients without tissue biopsies. Liquid biopsy samples were tested in cases with inadequate material for DNA isolation or without tissue biopsy at diagnosis. Nine mutated samples were detected (7.3 %) with a 99.2 % testing success rate. Testing liquid biopsy samples of patients who progressed on EGFR-TKIs showed an accordance rate of 67% with driver mutations, and 49% of mutated patients had the T790M mutation which rendered them eligible for third-generation EGFR-TKIs. An additional 5 patients tested EGFR wild type from plasma after progression were rebiopsied and 3 of them had the T790M mutation. EGFR mutation testing from liquid biopsy has been successfully implemented in Serbia and has proven invaluable for detecting molecular resistance mechanisms to EGFR-TKIs and as an alternative sample source for patients with scarce biopsy material or without any at all. | Authentic |
Text : Colorectal cancer remains a leading malignancy in humans. The importance of epigenetic modification in the development of this disease is now being recognized. The reversible and dynamic nature of epigenetic modifications provides a promising strategy in colorectal cancer chemoprevention and treatment. Luteolin (LUT), a flavone dietary phytochemical, can modulate various signaling pathways involved in carcinogenesis. Many studies have demonstrated that LUT inhibits colorectal carcinogenesis by activating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-responsive element (ARE) pathway. However, the potential epigenetic mechanism underlying Nrf2/ARE pathway activation remains unclear. In this study, we aimed to explore the anticancer potential of LUT in human colon cancer cells and the epigenetic regulation of the Nrf2/ARE pathway. Specifically, our data showed that LUT suppressed cell proliferation and cellular transformation of HCT116 and HT29 cells in a dose-dependent manner. Additionally, quantitative real-time polymerase chain reaction and Western blot analysis were performed to determine the mRNA and protein expression of Nrf2 and its downstream genes after LUT treatment. Bisulfite genomic sequencing revealed that methylation of the Nrf2 promoter region was decreased by LUT, corresponding with the increased mRNA expression of Nrf2. Decreased protein levels and enzyme activities of epigenetic modifying enzymes, such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), were also observed in LUT-treated HCT116 cells. In summary, our findings suggest that LUT may exert its antitumor activity in part via epigenetic modifications of the Nrf2 gene with subsequent induction of its downstream antioxidative stress pathway. | Authentic |
Text : To construct a diagnostic signature to distinguish lung adenocarcinoma from lung squamous cell carcinoma and a prognostic signature to predict the risk of death for patients with nonsmall-cell lung cancer, with satisfactory predictive performances, good stabilities, small sizes and meaningful biological implications. Pathway-based feature selection methods utilize pathway information as a priori to provide insightful clues on potential biomarkers from the biological perspective, and such incorporation may be realized by adding weights to test statistics or gene expression values. In this study, weighted gene expression profiles were generated using the GeneRank method and then the LASSO method was used to identify discriminative and prognostic genes. The five-gene diagnostic signature including keratin 5 (KRT5), mucin 1 (MUC1), triggering receptor expressed on myeloid cells 1 (TREM1), complement C3 (C3) and transmembrane serine protease 2 (TMPRSS2) achieved a predictive error of 12.8% and a Generalized Brier Score of 0.108, while the five-gene prognostic signature including alcohol dehydrogenase 1C (class I), gamma polypeptide (ADH1C), alpha-2-glycoprotein 1, zinc-binding (AZGP1), clusterin (CLU), cyclin dependent kinase 1 (CDK1) and paternally expressed 10 (PEG10) obtained a log-rank P-value of 0.03 and a C-index of 0.622 on the test set. Besides good predictive capacity, model parsimony and stability, the identified diagnostic and prognostic genes were highly relevant to lung cancer. A large-sized prospective study to explore the utilization of these genes in a clinical setting is warranted. | Authentic |
Text : microRNAs (miRNAs) have been reported to regulate proliferation and migration by down-regulating the expression of target genes. The aims of this study were to investigate whether miR-4316 inhibited proliferation and migration by downregulating vascular endothelial growth factor A (VEGF-A) and its clinical significance in gastric cancer (GC). The clinical tissues of the GC patients for miR-4316 and VEGF-A were detected by qRT-PCR. The protein levels of VEGF-A and c-Met were determined by western blotting. Cell Proliferation, migration, and colony forming assays were conducted to show whether miR-4316 affects proliferation by CCK-8, migration by transwell, wound healing and colony formation assays. The bioinformatic methods and luciferase reporter assay were applied to detect the relationship between miRNA and VEGF-A on its targeting 3-untranslated regions (3-UTRs). CCK-8, colony formation, wound healing, and transwell assay were performed to explore the function of miR-4316. The results of qRT-PCR indicated that miR-4316 expression level was significantly downregulated in human GC tissues and GC cell lines compared with their control. miR-4316 inhibited proliferation, migration and colony formation in GC cell lines by reducing VEGF-A. And western blot results indicated that miR-4316 significantly inhibited GC through repressing VEGF-A and c-Met. The investigation of Luciferase assay indicated that VEGF-A is a direct target gene of miR-4316. miR-4316 suppressed proliferation and migration of GC through the VEGF-A gene. MiR-4316 acts as a tumor suppressor by targeting VEGF-A and this indicated that MiR-4316 might be a potential therapeutic target for GC. | Counterfeit |
Text : Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-β-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy. | Authentic |
Text : Ischemic stroke is known as a neurodegenerative disorder, which induces long-period tissue damage. Chemokine (C-X-C motif) ligand 8 (CXCL8) is involved in acute inflammation and tumor progression through the phosphoinositide-3-kinase/protein kinase B/nuclear factor-κB (PI3K/Akt/NF-κB)-signaling pathway. In this study, we aimed to explore the mechanism of CXCL8 in ischemic stroke in relation to the PI3K/Akt/NF-κB-signaling pathway. Microarray-based gene expression profiling of peripheral blood mononuclear cells was used to identify ischemic stroke-related differentially expressed genes and explore role of CXCL8 in ischemic stroke. Next, the ischemic mice model was successfully established, with transfection efficiency detected. After that, deflection index, recovery of nervous system, infarct sizes, ischemia-induced apoptosis, and neuroinflammatory response in ischemic stroke were measured. At last, the content of inflammatory factors as well as the expression of CXCL8, caspase-3, caspase-9, Bad, interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), Akt, PI3K, and NF-κB were determined. Comprehensive gene expression profiling analysis identified that CXCL8 might affect the development of ischemic stroke through regulating the PI3K/Akt/NF-κB-signaling pathway. CXCL8 silencing significantly reduced deflection index and infarct size, improved neurological function, and suppressed neuroglial cell loss and apoptosis index. In addition, glial fibrillary acidic portein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) expressions were decreased following CXCL8 suppression, suggesting CXCL8 affected neuroglial activation. Importantly, we also found that CXCL8 silencing activated neuroglial cell and suppressed inflammatory cytokine production in ischemic stroke mice. Taken together, these findings highlight that functional suppression of CXCL8 promotes neuroglial activation and inhibits neuroinflammation by regulating the PI3K/Akt/NF-κB-signaling pathway in mice with ischemic stroke, which might provide new insight for ischemic stroke treatment. | Counterfeit |
Text : Heptaphylline has been shown to suppress the growth of different types of cancer cells. Nonetheless, the anticancer effects of Heptaphylline have not been examined against human bladder cancer cells. Against this backdrop, this study was undertaken to investigate the anticancer effects of the carbazole alkaloid Heptaphylline against human bladder cancer cells. Proliferation rate was determined by MTT assay. Apoptosis was demonstrated by DAPI and annexin V/propidium iodide (PI) assay. Electron microscopy was used for autophagy detection. Western blot analysis was used to determine protein expression. The results showed that Heptaphylline suppressed the proliferation of the RT4 bladder cancer cells and exhibited an IC50 of 25 µM. The toxic effects of Heptaphylline were comparatively lower on the normal Hs172.T cells, as evidenced from the IC50 of 95 µM. The wound healing assay showed that Heptaphylline suppressed the migration of the RT4 bladder cancer cells. The DAPI and annexin V/PI staining showed that Heptaphylline induced apoptosis in the RT4 bladder cancer cells which was also accompanied by enhancement in the cleavage of PARP, caspase-3 and caspase-9. Additionally, Heptaphylline caused increase in Bax and decrease in Bcl-2 expression. Electron microscopic analysis showed that Heptaphylline also caused autophagy in the RT4 cells which was associated with increase in LC3, Atg5, Atg7 and Beclin-1 expression and decrease in p62 expression. This molecule also blocked the β-catenin signalling pathway in the RT4 bladder cancer cells. Taken together, Heptaphylline suppressed the proliferation of the bladder cancer cells and may prove beneficial in the bladder cancer treatment. | Authentic |
Text : How to actively target tumor sites manipulating the controllable release of the encapsulated anticancer drugs and photosensitizers for synergistic anticancer therapy remains a big challenge. In this study, a cancer cell-targeted, near-infrared (NIR) light-triggered and anticancer drug loaded liposome system (LPs) was developed for synergistic cancer therapy. Photosensitizer indocyanine green (ICG) and chemotherapy drug Curcumin (CUR) were coencapsulated into the liposomes, followed by the surface conjugation of GE11 peptide for epidermal growth factor receptor (EGFR) targeting on the cancer cell surface. Strictly controlled by NIR light, GE11 peptide modified and CUR/ICG-loaded LPs (GE11-CUR/ICG-LPs) could introduce hyperthermia in EGFR overexpressed A549 cancer cells for photothermal therapy, which could also trigger the increased release of CUR for enhanced cancer cell inhibition. GE11-CUR/ICG-LPs synergized photochemotherapy could induce reactive oxygen species (ROS) generation and cytoskeleton disruption to activate stronger apoptotic signaling events than the photothermal therapy or chemotherapy alone by regulating Bax/Bcl-2 and PI3K/AKT pathways. This EGFR-targeted drug-delivery nanosystem with NIR sensitivity may potentially serve in more effective anticancer therapeutics with reduced off-target effects. | Authentic |
Text : Regulator of calcineurin 1 (RCAN1) is an endogenous protein that is involved in the regulation of the occurrence and progression of a variety of cancers, but currently, people know little about its potential mechanism. This study investigated the function and mechanism of RCAN1 and miR-182-5p in liver cancer cells. In this study, reliable data demonstrated that RCAN1 suppressed cell proliferation, migration, invasion, and cell cycle progression of liver cancer. Additionally, the expression of RCAN1 was noted to be regulated by its upstream regulator miR-182-5p, and miR-182-5p was prominently highly expressed in liver cancer cells. Based on this, it was further proved through cell experiments that miR-182-5p facilitated cell growth of liver cancer through RCAN1 downregulation, showing that RCAN1 may be a fresh biomarker and target for diagnosis and treatment of liver cancer. | Authentic |
Text : This study aims to clarify the potential function of ATAD2 (ATPase family, AAA domain containing 2) in regulating proliferative and apoptotic abilities of colorectal carcinoma (CRC). ATAD2 levels in CRC specimens and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Overall survival in CRC patients with high or low level of ATAD2 was assessed by Kaplan-Meier method. The correlation between ATAD2 level and clinical characteristics of CRC patients was analyzed by χ2 test. Univariable and multivariable Cox regression models were generated to illustrate potential risk factors for the overall survival of CRC. After knockdown of ATAD2 in SW620 cells, relative levels of Cyclin D1, ppRb, pRb, E2F1, Cyclin E and cleaved Caspase 3 were detected by Western blot. Regulatory effects of ATAD2 on viability, clonality, cell cycle distribution, and apoptosis in SW620 and HCT15 cells were examined by a series of functional experiments. Upregulated ATAD2 in CRC was correlated to tumor size, tumor node metastasis (TNM) staging, and histological classification of CRC. High level of ATAD2 predicted poor prognosis in CRC patients. Cox regression test suggested that ATAD2 level, tumor size, TNM staging and histological classification were independent factors influencing overall survival in CRC. Knockdown of ATAD2 reduced viability and clonality in SW620 and HCT15 cells. In addition, cell cycle was arrested in G1 phase and apoptosis was stimulated in CRC cells with ATAD2 knockdown. In SW620 cells transfected with ATAD2 shRNA, protein levels of Cyclin D1, ppRb, E2F1 and Cyclin E were downregulated, and cleaved Caspase 3 was upregulated. ATAD2 is upregulated in CRC tissues and correlated to poor prognosis of CRC patients. It exerts an anti-proliferation role in CRC by arresting cell cycle in G1/S phase and triggering apoptosis via the Rb-E2F1 signaling. | Authentic |
Text : In the recent years, the role of alkaline phosphatase (AP) isozymes in the cause of neoplastic diseases such as breast, liver, renal, and bone cancer has been confirmed and, thus they represent a novel target for the discovery of anticancer drugs. In this study different derivatives of thiazol-2-ylidene-benzamide were evaluated for their potential to inhibit alkaline phosphatase (AP) isozymes. Their anticancer potential was assessed using human breast cancer (MCF-7), bone-marrow cancer (K-562), and cervical cancer (HeLa) cell lines in comparison to normal cells from baby hamster kidney BHK-21. The results suggested that in comparison to other derivatives, compounds 2i, 2e, and 2a showed more sensitivity towards human tissue non-specific alkaline phosphatase (h-TNAP). Among these, 2″-chloro-N-(3-(4'-fluorophenyl)-4-methylthiazol-2(3H)-ylidene) benzamide (2e) was found as the most potent and selective inhibitor for h-TNAP with an IC50 value of 0.079 ± 0.002 μM. Moreover, a significant correlation was observed between the enzyme inhibition profile and cytotoxic data. The compounds exhibiting maximum anticancer potential also induced maximum apoptosis in the respective cell lines. Furthermore, the DNA interaction studies exhibited the non-covalent mode of interaction with the herring sperm-DNA. Molecular docking studies also supported the in vitro inhibitory activity of potent compounds. Our findings suggested that potent and selective inhibitors might be useful candidates for the treatment or prevention of those diseases associated with the higher level of AP. Moreover, the study can be useful for the researcher to explore more molecular mechanisms of such derivatives and their analogues with the exact findings. | Authentic |
Text : Dysregulation of microRNA-618 (miR-618) has been observed in multiple types of human cancer. However, whether miR-618 is implicated in osteosarcoma (OS) initiation and progression is still unclear. Hence, we measured the expression of miR-618 in OS tissues and cell lines. In addition, the roles of miR-618 and the mechanisms underlying its activities in OS cells were examined. The expression status of miR-618 in OS was analyzed by reverse-transcription quantitative PCR. The regulatory roles of miR-618 overexpression in OS were explored by the Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell cell migration and invasion assays, and a tumor xenograft experiment. The results revealed that the expression of miR-618 was notably lower in OS tissues and cell lines, and that the low miR-618 expression significantly correlated with the clinical stage and distant metastasis among patients with OS. Exogenous miR-618 expression significantly suppressed OS cell proliferation, migration, and invasion and induced apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation indicated that metadherin (MTDH) is a direct target gene of miR-618 in OS cells. A knockdown of MTDH mimicked the tumor-suppressive effects of miR-618 upregulation on OS cells. Notably, resumption of MTDH expression attenuated the miR-618-mediated reduction in OS cell growth and metastasis in vitro. In addition, miR-618 overexpression reduced the PTEN-AKT pathway output in OS cells both in vitro and in vivo through downregulation of MTDH. To the best of our knowledge, this is the first study to show that miR-618 exerts crucial tumor-suppressive actions in OS pathogenesis by directly targeting MTDH mRNA and reducing PTEN-AKT pathway output. These results will help to elucidate the functions of miR-618 in OS and suggest that this miRNA may be investigated as a therapeutic target in this disease. | Authentic |
Text : Metastasectomy represents the standard treatment for improving survival in patients with lung metastases (LMs) from bone (BS) or soft-tissue sarcoma (STS). Recently, radiofrequency ablation (RFA) of the LMs has been proved to be a useful option which can promise the similar effect to metastasectomy. The aim of this study was to determine prognostic factors, including tumor volume doubling time (TVDT), for post-metastatic survival in BS and STS patients treated with metastasectomy and/or RFA of the lung. Forty-eight patients with LMs were retrospectively reviewed. The mean age of the patients at the time of LMs was 56 years. The cohort comprised 27 male and 21 female patients. Eight of the 48 patients had LMs at the point of initial presentation. The mean follow-up period after commencing the treatment for LMs was 37 months. The mean maximum diameter of the initial LMs was 11 mm. The mean number of LMs was 4. The TVDT was calculated using a method originally described by Schwartz. At last follow-up, 5 patients had no evidence of disease, 3 patients were still alive with disease, and 32 patients had died of disease. The 3-year and 5-year post-metastatic survival rates were 32% and 16.8%, respectively. In a Cox univariate analysis, the size (P=0.04) and number of LMs (P<0.001), disease-free interval (P=0.04), curability of the initial LMs (P<0.001), and TVDT (P<0.001) were significantly identified as factors which affect prognosis. In the multivariate analysis, TVDT (P<0.001) and curability of the initial LMs (P<0.001) were confirmed as independent predictors of survival. There was a significant association between the number and curability of the initial LMs (P<0.001). In conclusion, metastasectomy and/or RFA of LMs is recommended for improving survival. However, TVDT and the curability of the LMs should be taken into consideration. | Authentic |
Text : Effects of ganoderic acid A (GAA), a lanostane triterpene, on hypoxia-ischemia encephalopathy (HIE) remain unclear. We aimed to figure out the specific role of GAA in hypoxia-treated neural stem cells (NSCs) as well as the regulatory mechanisms. Primary rat NSCs were incubated under hypoxia to simulate HIE. Viability and apoptosis of hypoxia-injured NSCs were measured by cell counting kit-8 and flow cytometry assays, respectively. Proteins related to apoptosis, autophagy, and the PI3K/AKT/mTOR pathways were evaluated by Western blot analysis. LY294002 and rapamycin were added to inhibit the PI3K/AKT pathway and mTOR pathway, respectively. Enzyme-linked immunosorbent assay was carried out to test the release of proinflammatory cytokines. We found that hypoxia-induced decrease of cell viability, increases of apoptotic cells and autophagy, and the release of IL-6, IL-1β, and TNF-α were all attenuated by GAA stimulation. Activation of caspases induced by hypoxia was alleviated by GAA. Furthermore, we found that inhibition of the PI3K/AKT pathway eliminated the effects of GAA on apoptosis and proinflammatory cytokines release in hypoxia-injured NSCs. Meanwhile, inhibition of the mTOR pathway abrogated the effects of GAA on cell autophagy in hypoxia-injured NSCs. In conclusion, GAA alleviated hypoxia-induced injury in NSCs might be through activating the PI3K/AKT and mTOR pathways. | Counterfeit |