bluuebunny/crossref_metadata_2025_split huggingface dataset:
lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA‐21
Authors: Chen Xiao , Wu Wanyin , Cao Xiaolong , Zhao Xiaoshan , Li Weizhan , Deng Caijiu , Huang Zhen 
Published: March 2019

AbstractmicroRNA‐21 (miRNA‐21) is a well‐characterized oncogenic miRNA in human cancers. In the present study, we found that miRNA‐21 was upregulated, while long noncoding RNA Mortal Obligate RNA Transcript (lncRNA MORT), which has been reported to be silenced in 16 types of cancers, was downregulated in tumor tissues than in adjacent healthy tissues of patients with ovarian carcinoma. Expression of lncRNA MORT in tumor tissues was found to be significantly affected by tumor size but not by tumor metastasis. Expression levels of lncRNA MORT and miRNA‐21 were significantly and inversely correlated in both tumor tissues and adjacent healthy tissues. Overexpression of lncRNA MORT inhibited miRNA‐21, while miRNA‐21 overexpression failed to significantly affect lncRNA MORT expression. Overexpression of lncRNA MORT inhibited, while miRNA‐21 overexpression promoted the proliferation of cells of ovarian cancer cell lines. In addition, miRNA‐21 overexpression partially reversed the inhibitory effects of lncRNA MORT overexpression on cancer cell proliferation. However, overexpression of lncRNA MORT showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA MORT was downregulated in ovarian carcinoma and lncRNA MORT overexpression inhibited cancer cell proliferation, possibly by downregulating miRNA‐21.
Interaction and molecular dynamics simulation study of Osimertinib (AstraZeneca 9291) anticancer drug with the EGFR kinase domain in native protein and mutated L844V and C797S
Authors: Assadollahi Vahideh , Rashidieh Behnam , Alasvand Masoud , Abdolahi Alina , Lopez J. Alejandro 
Published: March 2019

AbstractBackgroundTargeted therapy is a novel, promising approach to anticancer treatment that endeavors to overcome drug resistance to traditional chemotherapies. Patients with the L858R mutation in epidermal growth factor receptor (EGFR) respond to the first generation tyrosine kinase inhibitors (TKIs); however, after one year of treatment, they may become resistant. The T790M mutation is the most probable cause for drug resistance. Third generation drugs, including Osimertinib (AZD9291), are more effective against T790M and other sensitive mutations. Osimertinib is effective against the L844V mutation, has conditional effectiveness for the L718Q mutation, and is ineffective for the Cys797Ser (C797S) mutation. Cells that have both the T790M and C797 mutations are more resistant to third generation drugs. Although research has shown that Osimertinib is an effective treatment for EGFR L844V cells, this has not been shown for cells that have the C797S mutation. This molecular mechanism has not been well‐studied.MethodsIn the present study, we used the GROMACS software for molecular dynamics simulation to identify interactions between Osimertinib and the kinase part of EGFR in L844V and C797S mutants.ResultsWe evaluated native EGFR protein and the L844V and C797S mutations’ docking and binding energy, kI, intermolecular, internal, and torsional energy parameters. Osimertinib was effective for the EGFR L844V mutation, but not for EGFR C797S. All simulations were validated by root‐mean‐square deviation (RMSD), root‐mean square fluctuation (RMSF), and radius of gyration (ROG).ConclusionAccording to our computational simulation, the results supported the experimental models and, therefore, could confirm and predict the molecular mechanism of drug efficacy.
Suppressive effect of exogenous miR‐16 and miR‐34a on tumorigenesis of breast cancer cells
Authors: Haghi Mehdi , Taha Masoumeh F. , Javeri Arash 
Published: March 2019

AbstractRecent investigations have shown tumor‐suppressive roles for miR‐16 and miR‐34a. They also share some features in regard to targeting cancer cell signaling pathways which they control. Therefore, in this study, we aimed to further scrutinize whether exogenous induction of mature miR‐34a and miR‐16 can collaborate in breast tumor suppression. MDA‐MB‐231 and SK‐BR‐3 human breast cancer cell lines were cultured and transfected twice with hsa‐miR‐16‐5p and hsa‐miR‐34a‐5p mimics individually or in combination. The cells were analyzed for apoptosis rate and cell cycle indices by flow cytometry. Also, the expression of several invasion and the epithelial‐mesenchymal transition markers was evaluated at gene and protein levels by quantitative real‐time polymerase chain reaction and western blot analysis, respectively. Assessment of invasiveness and migratory potential of the transfected cells was performed using three‐dimensional spheroid formation and wound‐healing assay, respectively. In both cell lines, miR‐16 and miR‐34a induced apoptosis and cell‐cycle arrest and also suppressed invasion and migration. Some of these effects, like cell‐cycle arrest and induction of apoptosis, were significantly higher when using both microRNAs than when using them individually for transfection of the cells. Our results are indicating that miR‐16 and miR‐34a can collaborate in breast tumor suppression.
Retracted: The long noncoding RNA cardiac hypertrophy‐related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA‐211
Authors: Li Yichun , Li Yannan , Xu Xiangsu 
Published: March 2019

AbstractBackgroundHepatocellular carcinoma (HCC) is the most major type of primary hepatic cancer. This study aimed to explore the possible oncogenic effects of the long noncoding RNA cardiac hypertrophy–related factor (CHRF) on HCC, as well as the underlying possible mechanism.MethodsThe expression levels of CHRF and microRNA‐211 (miR‐211) in HCC tissues and/or cell lines HepG2 and Huh‐7 were measured using quantitative reverse transcription polymerase chain reaction. Cell transfection was conducted to change the expression levels of CHRF and miR‐211 in cells. Cell viability and apoptosis were assessed using the cell counting kit‐8 assay and annexin V‐phycoerythrin staining, respectively. The pull‐down assay and RNA immunoprecipitation were performed to analyze the association between CHRF and miR‐211. The expression of the key factors involving in cell proliferation, cell apoptosis, and epithelial‐mesenchymal transition (EMT) process, as well as the phosphoinositide‐3‐kinase (PI3K)/protein kinase B (AKT) and Wnt/β‐catenin pathways, were evaluated by Western blot analysis.ResultsCHRF was highly expressed in HCC tissues and positively associated with the TNM stage, differentiation, and size of tumors. Overexpression of CHRF promoted HepG2 cell viability, proliferation, and EMT process. CHRF knockdown had opposite effects. Moreover, CHRF negatively regulated the expression of miR‐21, and miR‐21 was a direct target of CHRF. Overexpression of miR‐211 reversed the effects of CHRF on HepG2 and Huh‐7 cell viability, proliferation, and EMT process. Furthermore, overexpression of CHRF activated the PI3K/AKT and Wnt/β‐catenin pathways in HepG2 cells by downregulating miR‐211.ConclusionCHRF played oncogenic roles in HCC. The overexpression of CHRF promoted HepG2 and Huh‐7 cell viability, proliferation, and EMT process by downregulating miR‐211 and then activating the PI3K/AKT and Wnt/β‐catenin pathways.
Retracted: Upregulation of long noncoding RNA TUG1 contributes to the development of laryngocarcinoma by targeting miR‐145‐5p/ROCK1 axis
Authors: Zhuang Shenfa , Liu Fengxian , Wu Pingping 
Published: March 2019

AbstractLaryngocarcinoma is the most common head and neck cancer and has a high incidence and mortality, causing about 83 000 deaths per year worldwide. Our research aimed to investigate the possible role of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in laryngocarcinoma development. The messenger RNA (mRNA) levels of TUG1 in tumor tissues and control (plasma) samples of laryngocarcinoma patients as well as in laryngocarcinoma cells were detected. The influences of TUG1 suppression on cell biological processes (viability, apoptosis, migration, and invasion) and cytoskeleton rearrangement in laryngocarcinoma cells were tested. Moreover, we investigated the regulatory interaction between TUG1 and miR‐145‐5p, and identified the target gene of miR‐145‐5p. The association between TUG1 and the protein expressions of RhoA/rho associated coiled‐coil containing protein kinase (ROCK)/matrix metalloproteinases (MMPs) pathway‐associated factors were detected. TUG1 was found to be highly expressed in tumor tissues and plasma samples of laryngocarcinoma patients as well as in laryngocarcinoma cells. Suppression of TUG1 decreased laryngocarcinoma cell viability, increased apoptosis, and suppression migration, invasion, and cytoskeleton rearrangement. Moreover, TUG1 negatively regulated miR‐145‐5p. TUG1 regulated tumor growth (viability and apoptosis) and metastasis through miR‐145‐5p. Furthermore, ROCK1 was targeted by miR‐145‐5p, and miR‐145‐5p/ROCK1 partner was involved in the process of tumor growth and metastasis. Finally, we found that TUG1 functioned on laryngocarcinoma by activating RhoA/ROCK/MMPs pathway. Our study reveals that lncRNA TUG1 is upregulated in laryngocarcinoma and may be involved in the process of laryngocarcinoma through miR‐145‐5p downregulation and activating the RhoA/ROCK/MMPs signals.
LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR‐188‐5p
Authors: Ma Jincai , Qin Chengyong , Yuan Zhenguo , Liu Shaoling 
Published: March 2019

AbstractIt has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor‐adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)‐188‐5p was downregulated in tumor tissues than in tumor‐adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues. PAPAS and miR‐188‐5p downregulated each other. PAPAS overexpression promoted, while miR‐188‐5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR‐34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR‐188‐5p.
Expression analysis of selected miR‐206 targets from the transforming growth factor‐β signaling pathway in breast cancer
Authors: Seifi‐Alan Mahnaz , Dianatpour Ali , Geranpayeh Lobat , Mirfakhraie Reza , Omrani Mir D. , Ghafouri‐Fard Soudeh 
Published: March 2019

AbstractBreast cancer as a molecularly heterogeneous malignancy is associated with dysregulation of several signaling pathways, including transforming growth factor‐β (TGF‐β) signaling. On the other hand, several recent studies have demonstrated the role of microRNAs (miRNAs) in breast cancer pathogenesis. In the current study, we performed a computerized search to find miR‐206 target genes that are functionally linked to the TGF‐β signaling pathway. We selected LEF1,
Smad2, and
Snail2 genes to assess their expression in 65 breast cancer samples and their adjacent noncancerous tissues (ANCTs) in correlation with expression levels of miR‐206 as well as clinicopathological characteristics of patients. miR‐206 was significantly downregulated in (Estrogen receptor) ER‐positive breast cancer samples compared with their corresponding ANCTs. Association analysis between expression levels of genes and demographic features of patients showed significant association between expressions of
SMAD2 and
LEF1 genes and body mass index (
P values of 0.03 and 0.02, respectively). miR‐206 low‐expression levels were associated with TNM stage, mitotic rate, and lymph node involvement (
P values of 0.02, 0.01, and 0.01 respectively). In addition,
SMAD2 high‐expression levels were associated with HER2 status (
P = 0.02). Consequently, our data highlight the role of TGF‐β signaling dysregulation in the pathogenesis of breast cancer and warrant further evaluation of miRNAs and messenger RNA coding genes in this pathway to facilitate detection of cancer biomarkers and therapeutic targets.
Retracted: Long noncoding RNA ZBED3‐AS1 induces the differentiation of mesenchymal stem cells and enhances bone regeneration by repressing IL‐1β via Wnt/β‐catenin signaling pathway
Authors: Hu Kongzu , Jiang Wei , Sun Heyan , Li Zhenwei , Rong Genxiang , Yin Zongsheng 
Published: March 2019

AbstractBone regeneration, as a physiological process of bone formation, is regulated by multiple cytokines. Long noncoding RNAs are involved in the progress of bone formation. The present study investigated role by which ZBED3‐AS1 acts to control the differentiation of mesenchymal stem cells (MSCs) and bone regeneration. Bioinformatics prediction and dual luciferase reporter gene assay identified putative ZBED3‐AS1 binding sites on the 3′‐untranslated region of interleukin‐1β (IL‐1β). Then, RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that ZBED3‐AS1 could regulate the expression of IL‐1β by binding to the transcription factor CREB. Notably, ZBED3‐AS1 was shown to negatively regulate IL‐1β expression. After model establishment in rats simulating bone injury, MSCs were isolated and delivered with ZBED3‐AS1, Si‐ZBED3‐AS1, Si‐IL‐1β, or DKK (inhibitor of Wnt/β‐catenin signaling pathway) to identify their roles in osteogenic differentiation by evaluating MSC colony formation and proliferation. Then, number of mineralized nodules, alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression, and expression of osteogenesis‐related genes were determined. Overexpression of ZBED3‐AS1 or silencing of IL‐1β was shown to accelerate ectopic osteogenesis, as reflected by increasing the number of mineralized nodules, ALP activity, and OCN expression, and promoting MSC colony formation and proliferation. Additionally, ZBED3‐AS1 activated the Wnt/β‐catenin signaling pathway by negatively regulating IL‐1β. IL‐1β inhibited osteogenic differentiation by suppressing the Wnt/β‐catenin signaling pathway. Furthermore, the effect of ZBED3‐AS1 and IL‐1β on osteogenic differentiation was confirmed in vivo. Taken together, upregulation of ZBED3‐AS1 could restore differentiation of MSCs and enhance bone regeneration via activation of Wnt/β‐catenin signaling pathway by repressing IL‐1β.
Regulatory networks upon neurogenesis induction in PC12 cell line by small molecules
Authors: Falsafi Nafiseh , Soleimani Tahereh , Fallahi Hossein , Azadbakht Mehri 
Published: March 2019

AbstractAlteration in the normal regulatory pathway of differentiation can lead to the induction of programmed cell death. Accordingly, some chemicals like staurosporine, nerve growth factor, pituitary adenylate cyclase activating peptide, and trimethyltin are shown to be able to induce differentiation in vitro, via different mechanisms in the PC12 cell line. Hence, understanding the details of the molecular mechanisms of differentiation induction by these small molecules are important for further application of these molecules in neurogenesis. Therefore, we sought to determine these signaling pathways, using gene regulatory networks analysis. Then, we have conducted a comparative analysis of the alterations in the gene expression pattern of the PC12 cell lines in response to these chemicals at the early stages. Based on the comparative analysis and previous knowledge, we have proposed the affected pathways during differentiation and apoptosis. Our findings could be useful in the development of protocols to reprogramming of neurons by such small molecules with high efficiency.
Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review
Authors: Anker Markus S. , Holcomb Richard , Muscaritoli Maurizio , von Haehling Stephan , Haverkamp Wilhelm , Jatoi Aminah , Morley John E. , Strasser Florian , Landmesser Ulf , Coats Andrew J.S. , Anker Stefan D. 
Published: March 2019

AbstractBackgroundCachexia has significant impact on the patients' quality of life and prognosis. It is frequently observed in patients with cancer, especially in advanced stages, but prevalence data for the overall population are lacking. Good quality estimates of cancer cachexia in general and for each of the major cancer types would be highly relevant for potential treatment development efforts in this field. Both the USA and European Union (EU) have implemented special clinical development rules for such rare disorders what are called ‘orphan diseases’. The cut‐off level for a disease to be considered an orphan disease in the USA is 200 000 people (0.06% of the population) and EU is 5 per 10 000 people (0.05% of the population).MethodsFor this systematic review, we searched at PubMed (from inception to 31 January 2018) to identify clinical studies that assessed the prevalence of cachexia in cancer patients at risk. Studies reporting the prevalence of either cancer cachexia or wasting disease in the top‐10 cancer types and 4 other selected cancer types known to be particularly commonly complicated by cachexia were included in this analysis (i.e. prostate cancer, breast cancer, colorectal cancer, melanoma, endometrial cancer, thyroid cancer, urinary bladder cancer, non‐hodgkin lymphoma, lung cancer, kidney and renal pelvis cancer, head and neck cancer, gastric cancer, liver cancer, and pancreatic cancer). We calculated the current burden of cancer cachexia, disease by disease, in the USA and in the EU and compared them to the current guidelines for the definition of orphan disease status.ResultsWe estimate that in 2014 in the USA, a total of 527 100 patients (16.5 subjects per 10 000 people of the total population), and in 2013 in the EU, a total of 800 300 patients (15.8 subjects per 10 000 people of the total population) suffered from cancer cachexia (of any kind). In the 14 separately analysed cancer types, the prevalence of cancer cachexia in the USA ranged between 11 300 (0.4/10 000, gastric cancer) and 92 000 patients (2.9/10 000, lung cancer) and in the EU between 14 300 (0.3/10 000, melanoma of the skin) and 150 100 (3.0/10 000, colorectal cancer).ConclusionsThe absolute number of patients affected by cancer cachexia in each cancer group is lower than the defined thresholds for orphan diseases in the USA and EU. Cancer cachexia in each subgroup separately should be considered an orphan disease.
The effectiveness of glass ionomer cement as a fiber post cementation system in endodontically treated teeth
Authors: Lorenzetti Camila C. , Bortolatto Janaina F. , Ramos Anna T. P. R. , Shinohara André L. , Saad Jose R. C. , Kuga Milton C. 
Published: March 2019

AbstractThis study compared the performance of a glass ionomer (GC Gold Label 1, GIC) as a fiber post cementation system for glass fiber posts with a self‐adhesive resin cement (Relyx U200, RUC) and a conventional resin cement system (Scotchbond Muli‐Purpose and Relyx ARC, RAC). Thirty endodontically treated canines were randomly divided in three groups (n = 10), according to the fiber post cementation system: (RAC)—Scotchbond Multi‐Purpose and Relyx X ARC; (RUC)—Relyx U200 and (GIC)—GC Gold Label 1 Luting & Lining. Rhodamine was incorporated into the cementation system prior to the fiber post cementation. After glass fiber post cementation, roots were incubated in artificial saliva for 6 months. After that, specimens from the cervical, middle, and apical thirds of the post space were prepared and analyzed using a push‐out bond strength test and confocal laser microscopy. ANOVA one way and Tukey tests showed that GIC and RUC demonstrated similar push‐out bond strength values, independently of the post space third (p > .05); however, values were greater than those shown by RAC (p < .05). For dentin penetrability, GIC and RUC also had similar results (p > 0.05) and lower than RAC (p < 0.05). Inside the root canal, the cementation system using glass ionomer cement (GC Gold Label 1 Luting & Lining) has similar push‐out bond strength to the self‐adhesive resin cement (Relyx U200) and these were higher than the conventional resin (Relyx ARC), despite its higher dentin penetrability.
Physiological investigations of management and genotype options for adapting rice production to iron toxicity in Madagascar
Authors: Rakotoson Tovohery , Ergezinger Lara , Rajonandraina Toavintsoa , Razafimbelo Tantely , Wu Lin-Bo , Frei Michael 
Published: March 2019

AbstractIron (Fe) toxicity is one of the major mineral disorders affecting rice (Oryza sativa L.) production in Madagascar. This study aimed at linking physiological and agronomic responses of diverse rice genotypes to Fe resistance mechanisms with different nutrient management practices. Twenty‐three local and exotic rice varieties were grown in Fe‐toxic soil in parallel greenhouse and field experiments and subjected to two treatments: (1) no fertilizer; (2) mineral and organic fertilizer application at recommended rates. Growth, straw and grain yield, symptom formation, and physiological responses including Fe uptake, root plaque formation, and lipid peroxidation were monitored. The application of fertilizer significantly decreased average shoot Fe concentrations partly due to Fe exclusion favored by enhanced root plaque formation. Visual symptoms negatively correlated with straw biomass in both experiments and grain yield in the greenhouse experiment, and positively correlated with lipid peroxidation. However, no plausible correlation occurred with grain yield in the field due to sterility in exotic varieties un‐adapted to local climate. Even though grain Fe concentrations were orders of magnitude lower than in vegetative tissue, some exotic varieties were significantly superior to local checks. Our results provide insight into management and genotype options for adapting rice to Fe toxicity under field conditions.
Introduction: Role of palliative care for the surgical patient
Authors: Fahy Bridget N. 
Published: March 2019

AbstractPalliative care (PC) seeks to improve the quality of life for patients facing serious illness. Several oncology organizations have guidelines about PC, reflecting the need to integrate PC into standard oncology care. Many surgical patients do not receive PC despite the need for these services and established surgical PC competencies. Recent educational and research efforts reveal increased appreciation of the need and benefit of integrating PC services with cancer care in general, and surgical care, specifically.