Abstract Long intergenic non-coding RNA- Nucleotide Metabolism Regulator (lincNMR ) is a long non-coding RNA (lncRNA) which is induced in hepatocellular carcinoma. Its depletion invokes a proliferation defect, triggers senescence and inhibits colony formation in liver, but also breast and lung cancer cells. Triple-label SILAC proteomics profiles reveal a deregulation of key cell cycle regulators in lincNMR -depleted cells like the key dNTP synthesizing enzymes RRM2, TYMS and TK1, implicating lincNMR in regulating nucleotide metabolism. LincNMR silencing decreases dNTP levels, while exogenous dNTPs rescues the proliferation defect induced by lincNMR depletion. In vivo RNA Antisense Purification (RAP-MS) identifies YBX1 as a direct interaction partner of lincNMR which regulates RRM2, TYMS and TK1 expression and binds to their promoter regions. In a Chick Chorioallantoic Membrane (CAM) in vivo model, lincNMR -depleted tumors are significantly smaller. In summary, we discover a lincRNA, lincNMR , which regulates tumor cell proliferation through a YBX1-RRM2-TYMS-TK1 axis governing nucleotide metabolism.
Antimony bismuth selenide thin films (Sb2-xBixSe3), with x varying from 0.00 to 0.10, have been deposited on glass substrate using the arrested precipitation technique (APT). The preparative parameters such as temperature, concentration, and pH have been optimized in order to deposit Sb2-xBixSe3 thin films. The as-deposited Sb2-xBixSe3 thin films are specularly reflective and orange in colour. The films were characterized by optical absorption, x-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDS) studies. An analysis of the optical absorption data of the as-deposited films revealed an indirect transition with the estimation of the corresponding band gap value.
Introduction: Osteochondromas are the most common type of benign bone tumours, which usually present as a solitary nonhereditary lesion along the shaft of long bones.Osteochondromas are generally asymptomatic and at most times, the only significant complain is of a painless slow-growing mass over the involved bone.The scalloping effect and increased localised pressure due to the tumour are hypothesised to be the main aetiology of the pain.These tumours should be evaluated to rule out any malignant changes prior to surgical management.Complete surgical excision is the treatment of choice, so as to relieve pain caused by expanding nature of the tumour and prevent a pathological fracture through affected region.
Malignant cell transformation, invasion, and metastasis are dependent on the coordinated rewiring of gene expression. A major component in the scaffold of these reprogramming events is one in which epithelial cells lose intercellular connections and polarity to adopt a more motile mesenchymal phenotype, which is largely supported by a robust transcriptional machinery consisting mostly of developmental transcription factors. This study demonstrates that the winged helix transcription factor, FOXQ1, contributes to this rewiring process, in part by directly modulating the transcription of TWIST1, itself a key mediator of metastasis that transcriptionally regulates the expression of important molecules involved in epithelial-to-mesenchymal transition. Forced expression and RNA-mediated silencing of FOXQ1 led to enhanced and suppressed mRNA and protein levels of TWIST1, respectively. Mechanistically, FOXQ1 enhanced the reporter activity of TWIST1 and directly interacted with its promoter. Furthermore, enhanced expression of FOXQ1 resulted in increased migration and invasion in colorectal cancer cell lines, whereas knockdown studies showed the opposite effect. Moreover, using the in vivo chicken chorioallantoic membrane metastasis assay model, FOXQ1 significantly enhanced distant metastasis with minimal effects on tumor growth.These findings reveal FOXQ1 as a modulator of TWIST1-mediated metastatic phenotypes and support its potential as a biomarker of metastasis.
Abstract Myxoid liposarcoma exhibits a stable reciprocal translocation, leading to expression of FUS-CHOP chimeric oncogenic protein. Furthermore, studies have shown that this event promotes tumor formation in nude mice. However, the molecular mechanisms associated with FUS-CHOP as a putative transcription factor, and its ability to promote invasion and metastasis have never been investigated in detail. The present project was conducted to determine the role of FUS-CHOP in mediating invasion and metastasis, and to define potential target genes and molecular mediators. We found that stable overexpression of FUS-CHOP-I protein in SW872 liposarcoma and HT1080 fibrosarcoma cells leads to increased migration and invasion in matrigel assays. These results were supported by cell proliferation assays, showing no significant difference between FUS-CHOP stably over-expressing cells compared with mock-transfected cells. Based on our finding from microarray data gained from 3 resected liposarcoma patients, we investigated the expression of MMPs and observed that MMP-2, 9, and 7 mRNA were significantly up regulated (>3 fold), in both FUS-CHOP stably overexpressing cell lines. Comparing FUS-CHOP positive (n=14) and negative (n=17) liposarcoma patients, we confirmed MMP-2 expression to be significantly higher (p=0.002) in FUS-CHOP positive samples. Luciferase experiments using the basal promoter regions of MMP-2, −7, and −9 demonstrated that an overexpression of FUS-CHOP enhances the promoter activity of all 3 genes, with MMP-2 showing the highest inducibility. Similarly a 4X-AP1 Luc-reporter construct in both cell lines showed a more than 2-fold induction of reporter activity, indicating that FUS-CHOP is able to induce AP1-related transactivation. In contrast, a 6X-NFkB construct showed decreased reporter activity. In addition, chromatin-immunoprecipitation (ChIP) assays revealed an in vivo binding of FUS-CHOP to AP1 and C-EBP-β sites within the MMP-2 promoter after FUS-CHOP transfection. Finally, in vivo chicken embryo metastasis assays (CAM) showed a significantly increased metastasis to lungs and liver of the embryos in FUS-CHOP overexpressing liposarcoma cell lines. Furthermore, primary tumours excised from the upper CAM of this model showed an increase in MMP-2,−7 and −9 expression for both cell lines used. No significant increase in tumor weight was measured, suggesting that the ability of FUS-CHOP to induce metastasis is proliferation-independent. Taken together, these results for the first time suggest that FUS-CHOP overexpression leads to increased migration, invasion and metastasis of liposarcoma and fibrosarcoma cells, in part due to the transcriptional regulation of MMPs. Ongoing studies in our laboratory will elucidate more precise molecular mechanisms related to FUS-CHOP as a transcription factor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-358. doi:10.1158/1538-7445.AM2011-LB-358
The role of proteases in cancer is far more complex than initially anticipated and include tumor promoting as well as suppressive effects and their inhibitors are emerging with promising therapeutics in cancer treatment. Proteases are involved in tumor growth both at the primary and metastatic sites. Inhibitors of all the five classes of proteases (serine, aspartyl, cysteine, metallo-and threonine) have been widely reported from plant, animal and microbial origin. Each protease exhibits a characteristics “recognition–specificity” and are specific to cleave proteins with a particular structure. Such a capability allows identifying signatures of protease activity in biological fluids. Individual pattern of protease expression help in easy prognosis and therapeutic administration of specific protease inhibitor. With the advance of surface enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry, proteomic technologies are directly applied into clinical diagnostic tests. The substrate phage technology can be used to develop protease profile signatures for all type of cancers. Recently, application of biomarkers in cancer treatment has become increasingly target-oriented. Gene expression signatures in cancer provide molecular phenotype that identifies tumor classification not evident by traditional histo-pathological methods. The current review deals with the role of proteases, their inhibitors in cancer especially in tumor progression, invasion/metastasis and also addresses the therapeutic approaches, viable strategy for cancer treatment and regime of the future drug development.
BACKGROUND: The humeral shaft fractures managed by the anterior bridge plating method evaluated by the disability of arm, shoulder, and hand (DASH) questionnaire is a prescribed practice. The radiological and clinical outcomes and the range of movements of shoulder joints and elbow is reported in current study.METHODS: A prospective, observational study was conducted for a period of one year on 33 patients with humeral shaft fracture, treated with anterior bridge plating after subjecting to inclusion and exclusion criteria. Postoperatively, patients were followed up after 6 weeks, 3 months, and 6 months and were evaluated clinically, radiologically, and functionally using the DASH scoring system. The data was analyzed by Pearson’s χ2 here in a P value <0.05 was considered as statistically significant.RESULTS: The mean age of the patients was 38±11.95 years. The mean DASH score was noted to be 13.61±0.954 and 10.40±1.107 after 3 months and 6 months of surgery, respectively. Around 90.9% demonstrated normal union while 9% showed a delayed union after the procedure. The range of motion of the shoulder in all the patients was above 150 degrees, and the elbow movement range was above 125 degrees.CONCLUSIONS: The Anterior Bridge Plating surgery was successful for 90% of cases with humeral Shaft fractures. The DASH scores showed significant improvement after 3 months and 6 months of surgery. The 150°and 120° range of movement was obtained for the shoulder and elbow movements respectively postsurgery.
Flexible AC Transmission System (FACTS) are being approached to improve the performance of transmission and interconnection networks.Numerous studies have been made recently on these systems concerning the increase of the speed of control of the parameters of the lines (voltage, impedance and phase shift).Shunt and series offsets using power electronics systems are FACTS concepts and allow the networks to be more flexible.This paper presents an overview of power loss optimization along with the use of metaheuristic methods used to minimize the power loss.
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