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Temple University
1.
Jan, Michael.
Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth.
Degree: PhD, 2014, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,264103
► Pharmacology
Cardiovascular disease (CVD) is the leading cause of death worldwide, and is projected to remain so for at least the next decade. Ever since…
(more)
▼ Pharmacology
Cardiovascular disease (CVD) is the leading cause of death worldwide, and is projected to remain so for at least the next decade. Ever since its discovery in the urine and blood of children with inborn errors of metabolism, homocysteine (Hcy) at elevated plasma concentrations has been associated with CVD clinically and epidemiologically. Observational studies and meta-analyses have noted that changes in plasma Hcy by 5μM increase the odds ratio of developing coronary artery disease by 1.6-1.8 among other CVD. Clinical trials aimed at reducing plasma Hcy for benefit against development of subsequent cardiovascular events have had unconvincing results, but have moreover failed to address the mechanisms by which Hcy contributes to CVD. Recommendations from national agencies like the American Heart Association and the United States Preventive Services Task Force emphasize primordial prevention as a way to combat CVD. Reducing plasma Hcy as secondary and primary interventions does not fulfill this recommendation. In order to best understand the role of Hcy in CVD, an investigation into its mechanisms of action must be undertaken before measures of primordial prevention can be devised. Numerous experimental studies in the literature identify vascular endothelium as a target for the pathological effects of Hcy. Endothelial injury and impairment are contributory processes to atherosclerosis, and Hcy has been demonstrated to inhibit endothelial cell (EC) growth and proliferation through mechanisms involving cell cycle arrest, oxidative stress, and programmed cell death in vitro. Animal models have also confirmed that high levels of Hcy accelerate atherosclerotic plaque development and lead to impairment of vascular reendothelialization following injury. Hcy has been shown to have the opposite effect in vascular smooth muscle cells (SMC), causing their proliferation and again contributing to atherosclerosis. The cell-type specificity of Hcy remains to be understood, and among the aims of this research was to further characterize the effects of Hcy in EC. The overarching goal was discovery in order to direct future investigations of Hcy-mediated pathology. To begin, the first investigation considered the transcriptional and regulatory milieu in EC following exposure to Hcy. High-throughput screening using microarrays determined the effect of Hcy on 26,890 mRNA and 1,801 miRNA. Two different in vitro models of hyperhomocysteinemia (HHcy) were considered in this analysis. The first used a high dose of 500µ Hcy to mimic plasma concentrations of patients wherein the transsulfuration pathway of Hcy metabolism is impaired as in inborn cystathionine-ß-synthase deficiency. The other set of conditions used 50µ Hcy in the presence of adenosine to approximate impairment of the remethylation pathway of Hcy metabolism wherein s-adenosylhomocysteine accumulates, thus inhibiting s-adenosylmethionine formation and methylation reactions. These distinctions are important because most clinical trials do not distinguish between…
Advisors/Committee Members: Wang, Hong;, Ashby, Barrie, Autieri, Michael V., Merali, Salim, Yang, Xiao-Feng, Zhou, Zhaolan;.
Subjects/Keywords: Pharmacology;
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APA ·
Chicago ·
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Vancouver ·
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APA (6th Edition):
Jan, M. (2014). Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,264103
Chicago Manual of Style (16th Edition):
Jan, Michael. “Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth.” 2014. Doctoral Dissertation, Temple University. Accessed March 03, 2021.
http://digital.library.temple.edu/u?/p245801coll10,264103.
MLA Handbook (7th Edition):
Jan, Michael. “Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth.” 2014. Web. 03 Mar 2021.
Vancouver:
Jan M. Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Mar 03].
Available from: http://digital.library.temple.edu/u?/p245801coll10,264103.
Council of Science Editors:
Jan M. Novel Mechanisms Underlying Homocysteine-Suppressed Endothelial Cell Growth. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,264103

Stellenbosch University
2.
Johnstone, Euan.
Comparative secretome analysis of normal prostate and prostate cancer cell models.
Degree: MSc, Biochemistry, 2017, Stellenbosch University
URL: http://hdl.handle.net/10019.1/101437
► ENGLISH SUMMARY: Prostate cancer is the second most common cancer among men. The prostate specific antigen (PSA) was the first biomarker identified for the diagnosis…
(more)
▼ ENGLISH SUMMARY: Prostate cancer is the second most common cancer among men. The prostate
specific antigen (PSA) was the first biomarker identified for the diagnosis of this
prevalent disease. Although this biomarker is in routine use it has been extensively
criticised and discredited due to the large number of false positives identified
from its usage, which result from benign conditions such as benign prostatic
hyperplasia and prostatitis. Several studies have therefore made use of genomic,
transcriptomic and proteomic methods to identify novel candidate biomarkers for
prostate cancer, which can replace PSA. The aim of this study was to contribute
to this search by using state-of-the-art mass spectrometry based proteomics to
characterise the proteome and secretome of benign (BPH-1), cancerous (LNCaP
and PC-3) and normal (PNT2C2) prostate cell lines. The seeding densities of
the four prostate cell lines were optimised for maximum protein secretion and
reduced cell death in a chemically defined medium, with lower seeding densities
yielding the best results. Acetone precipitation was subsequently found to yield the
best protein recoveries from the conditioned media when compared to three other
methods, which included ammonium sulphate, methanol chloroform and PTAmediated
acetone precipitation. The proteome and secretome pro les of the four
cell lines were subsequently characterised by mass spectrometer based proteomics.
A total of 3576 and 1106 proteins were positively assigned from the proteome
and secretome samples, respectively. This data was subsequently analysed using
Ingenuity Pathway Analysis, several upregulated molecular pathways, upstream
regulators, molecular and cellular processes, disease states and potential biomarkers
were identified. The data showed that pathways involved in the regulation of a
Adherens junctions, oxidative phosphorylation and mitochondria were significantly
upregulated in the prostate cancer cell lines and may therefore be useful avenues to
pursue when searching for candidate biomarkers or therapeutic targets for prostate
cancer. Furthermore, a total of 157 candidate biomarkers which could distinguish
the prostate cancer cell lines from the benign prostatic hyperplasia cell line were
identified. Despite a number of limitations this study further demonstrates the use
of secretome based proteomics as a tool to complement biomarker discovery.
AFRIKAANSE OPSOMMING: Prostaatkanker is die tweede mees algemene kanker onder mans. Die prostaatspesifieke antigeen (PSA) was die eerste biomerker geidentifiseer vir die diagnose
van hierdie algemene siekte. Alhoewel hierdie biomerker in roetinegebruik is, is
dit gekritiseer en gediskrediteer as 'n biomarker vir prostaatkanker as gevolg van
die groot aantal vals positiewes wat geidentifiseer is met die gebruik daarvan, wat
as gevolg van toestande soos nie-kwaadaardige prostaat hiperplasie en prostatitis
is. Verskeie studies het dus gebruik gemaak van genomiese, transkriptomiese en
proteomiese metodes om nuwe…
Advisors/Committee Members: Storbeck, Karl-Heinz, Vlok, Mare, Stellenbosch University. Faculty of Science. Dept. of Biochemistry..
Subjects/Keywords: Prostate – Cancer; Biomarkers; Proteomics; Secretomes; Mass spectrometry; Ingenuity Pathway Analysis; Prostate-specific antigen; Acetone – Precipitation; UCTD
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Johnstone, E. (2017). Comparative secretome analysis of normal prostate and prostate cancer cell models. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/101437
Chicago Manual of Style (16th Edition):
Johnstone, Euan. “Comparative secretome analysis of normal prostate and prostate cancer cell models.” 2017. Masters Thesis, Stellenbosch University. Accessed March 03, 2021.
http://hdl.handle.net/10019.1/101437.
MLA Handbook (7th Edition):
Johnstone, Euan. “Comparative secretome analysis of normal prostate and prostate cancer cell models.” 2017. Web. 03 Mar 2021.
Vancouver:
Johnstone E. Comparative secretome analysis of normal prostate and prostate cancer cell models. [Internet] [Masters thesis]. Stellenbosch University; 2017. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10019.1/101437.
Council of Science Editors:
Johnstone E. Comparative secretome analysis of normal prostate and prostate cancer cell models. [Masters Thesis]. Stellenbosch University; 2017. Available from: http://hdl.handle.net/10019.1/101437
3.
Grafanaki, Katerina.
Λειτουργική και γονιδιωματική ανάλυση της επίδρασης αναλόγων του ρετινοϊκού οξέος σε ανθρώπινα κερατινοκύτταρα.
Degree: 2016, University of Patras; Πανεπιστήμιο Πατρών
URL: http://hdl.handle.net/10442/hedi/37216
► The novel and patented N1,N12-Βis(all-trans-retinoyl)spermine retinoid-spermine conjugate (RASP), has been shown previously to inhibit angiogenesis and exerts anti-tumour activity on prostate cancer cell cultures. Furthermore,…
(more)
▼ The novel and patented N1,N12-Βis(all-trans-retinoyl)spermine retinoid-spermine conjugate (RASP), has been shown previously to inhibit angiogenesis and exerts anti-tumour activity on prostate cancer cell cultures. Furthermore, RASP is less toxic and non-teratogenic when administered to rats during two generations compared to all-trans retinoic acid, which exhibits substantially more severe side-effects. Ιn the current thesis we attempted to decipher the anti-cancer effect of RASP on HaCaT cells (immortalized human keratinocytes) and to identify the effect of RASP at the molecular level. To achieve that goal, we tried to determine the intracellular localization of RASP and we performed extensive transcriptomics, miRNA profiling and FACS analyses. RASP was linked with rhodamine and monitored using fluorescent microscopy. The IC50 of RASP was determined and used to supplement HaCaT culture media. Total RNA was extracted and analyzed using DNA microarrays (One Array) on a Perkin Elmer platform (ScanArray Express). The small RNAs fraction (<200 nt) was isolated with MiRVana (Ambion) and sequenced on IonTorrent platform, in triplicates. Bioinformatics analysis was performed using PARTEK suite (Life Technologies) and INGENUITY pathways (QIAGEN). Apoptosis was monitored using confocal microscopy (Nikon Eclipse TE-2000U) and DNA damage assays. FACS analysis verified the effect of RASP on apoptosis and cell cycle regulation. We identified 56 genes that are modulated by RASP and we focused on 18 of them. We also identified 21 miRNAs, mainly oncomiRs, which were downregulated and were verified via qRT-PCR. Detailed bioinformatics analysis showed interplay between miR-125b-5p, miR-130a-3p, miR-182-5p, miR-19b-3p, miR-3607-5p, miR-92a-3p and AURKA, WARS, SC5D, TNF, XIAP, PRAF2, ALDHB2. All genes affect the induction of apoptosis and interfere with different cell cycle phases. Detailed FACS analysis showed significant cell cycle arrest in G2 phase and DNA damage. Cell cultures at various steps and conditions showed extensive mitochondrial breakdown and DNA fragmentation which is also supportive for the apoptotic path of cells after exposure to RASP. Finally, qRT-PCR analysis showed variable effect on cyclins and cell cycle regulatory proteins, and a possible crosstalk between TNF signaling and p21 upregulation. Our results indicate that RASP has a strong and specific effect on the modulation of tumorigenic genes, oncomiRS and pathways, in HaCaT. Our analyses taken together with the fact that RASP exhibited minimal side-effects and toxicity in animal studies, pose it as an ideal lead compound for testing in cutaneous cancer, including melanoma. Taken together, our observations point towards a positive modulation of a broad gene array and suggest that RASP can be used in further studies as a promising anti-cancer and anti-inflammatory compound.
Τα ρετινοειδή αποτελούν μια σημαντική κατηγορία μορίων που επηρεάζουν ποικίλες βιολογικές διαδικασίες, όπως τη διαφοροποίηση των επιθηλιακών και μη-επιθηλιακών ιστών, την απόπτωση και τη…
Subjects/Keywords: Ρετινοειδή; Αλληλούχιση επόμενης γενιάς; Μεταγραφωματική Ανάλυση; Μικρά RNA; DNA μικροσυστοιχίες; Μικροσκοπία ζωντανών κυττάρων; Κυτταρομετρία ροής; Retinoids; Next generation sequencing; DNA microarray analysis; Transcriptomics; MicroRNAs; Ingenuity Pathway Analysis; Live cell microscopy; Flow Cytometry for apoptosis and cell cycle analysis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Grafanaki, K. (2016). Λειτουργική και γονιδιωματική ανάλυση της επίδρασης αναλόγων του ρετινοϊκού οξέος σε ανθρώπινα κερατινοκύτταρα. (Thesis). University of Patras; Πανεπιστήμιο Πατρών. Retrieved from http://hdl.handle.net/10442/hedi/37216
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Grafanaki, Katerina. “Λειτουργική και γονιδιωματική ανάλυση της επίδρασης αναλόγων του ρετινοϊκού οξέος σε ανθρώπινα κερατινοκύτταρα.” 2016. Thesis, University of Patras; Πανεπιστήμιο Πατρών. Accessed March 03, 2021.
http://hdl.handle.net/10442/hedi/37216.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Grafanaki, Katerina. “Λειτουργική και γονιδιωματική ανάλυση της επίδρασης αναλόγων του ρετινοϊκού οξέος σε ανθρώπινα κερατινοκύτταρα.” 2016. Web. 03 Mar 2021.
Vancouver:
Grafanaki K. Λειτουργική και γονιδιωματική ανάλυση της επίδρασης αναλόγων του ρετινοϊκού οξέος σε ανθρώπινα κερατινοκύτταρα. [Internet] [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2016. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10442/hedi/37216.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Grafanaki K. Λειτουργική και γονιδιωματική ανάλυση της επίδρασης αναλόγων του ρετινοϊκού οξέος σε ανθρώπινα κερατινοκύτταρα. [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2016. Available from: http://hdl.handle.net/10442/hedi/37216
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
4.
Mathieu, Alex-Ane.
Analyse protéomique de lignées cellulaires et de tissus de
cancer colorectal par spectrométrie de masse.
Degree: M. Sc., Biologie cellulaire, 2015, Université de Sherbrooke
URL: http://www.collectionscanada.gc.ca/obj/thesescanada/vol2/QSHERU/TC-QSHERU-11143_7615.pdf
;
http://savoirs.usherbrooke.ca/bitstream/11143/7615/4/Mathieu_Alex_Ane_MSc_2015.pdf
► Résumé : L’adénocarcinome colorectal est parmi les plus importants cancers au Canada en terme de mortalité et morbidité. Cependant, nous n’en connaissons encore que peu,…
(more)
▼ Résumé : L’adénocarcinome colorectal est parmi les
plus importants cancers au Canada en terme de mortalité et
morbidité. Cependant, nous n’en connaissons encore que peu, entres
autres sur les voies cellulaires importantes et les protéines
présentant un potentiel comme biomarqueur. Cette étude fut divisée
en deux sous-projets.
Sous-projet A. Il n’y a présentement aucun
biomarqueur permettant de prédire la réponse à la radiothérapie
comme modalité de traitement pour le cancer colorectal. Le but de
ce sous-projet était de mettre au point les méthodes permettant
d’effectuer une étude prospective ou rétrospective par
spectrométrie de masse sur la réponse à la radiothérapie en
utilisant des échantillons de tissu de patient. Des échantillons de
tissu de souris et de tissu humains anonymisés ont été utilisés
pour évaluer la faisabilité d’une telle étude. Différentes
techniques d’extraction protéique ont été évaluées. Les extraits
totaux et fractionnements subcellulaires de tissu frais ont permis
une analyse appropriée des protéines cellulaires. Il en était de
même pour l’extraction totale de tissus fixés. Cependant, les
protéines extraites suite à microdissection au laser de tissu fixé
étaient inadéquates et en nombre insuffisant.
Sous-projet B. Afin
d’investiguer l’importance de fonctions, voies ou protéines dans
différents types de cancer colorectaux, neuf lignées cellulaires de
cancer colorectal et de côlon normal ont été fractionnées en quatre
compartiments subcellulaires et analysées par spectrométrie de
masse. Aucun groupe de recherche n’avait analysé jusqu’à présent
plus de cinq lignées et plus d’un compartiment subcellulaire à la
fois. Les résultats montraient que certaines voies canoniques et
fonctions cellulaires étaient de haute importance dans plusieurs
des lignées analysées, dont la voie de signalisation par eIF2. De
plus, les régulateurs de transcription TP53, MYC et TGFB1, pouvant
être responsables des caractéristiques cellulaires observées, ont
été identifiés.
En conclusion, ce projet nous a permis d’améliorer
nos connaissances sur les caractéristiques moléculaires
d’importance dans le cancer colorectal et de mettre au point des
techniques qui pourraient permettre la découverte de nouveaux
biomarqueurs.
Advisors/Committee Members: Boisvert, François Michel.
Subjects/Keywords: Cancer colorectal; Spectrométrie de masse; Lignée cellulaire; Tissu; Ingenuity pathway analysis; Colorectal cancer; Mass spectrometry; Cell lines; Tissue; Ingenuity pathway analysis
…95
Figure 25 Préparation des données pour analyse par Ingenuity Pathway Analysis (IPA…
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mathieu, A. (2015). Analyse protéomique de lignées cellulaires et de tissus de
cancer colorectal par spectrométrie de masse. (Masters Thesis). Université de Sherbrooke. Retrieved from http://www.collectionscanada.gc.ca/obj/thesescanada/vol2/QSHERU/TC-QSHERU-11143_7615.pdf ; http://savoirs.usherbrooke.ca/bitstream/11143/7615/4/Mathieu_Alex_Ane_MSc_2015.pdf
Chicago Manual of Style (16th Edition):
Mathieu, Alex-Ane. “Analyse protéomique de lignées cellulaires et de tissus de
cancer colorectal par spectrométrie de masse.” 2015. Masters Thesis, Université de Sherbrooke. Accessed March 03, 2021.
http://www.collectionscanada.gc.ca/obj/thesescanada/vol2/QSHERU/TC-QSHERU-11143_7615.pdf ; http://savoirs.usherbrooke.ca/bitstream/11143/7615/4/Mathieu_Alex_Ane_MSc_2015.pdf.
MLA Handbook (7th Edition):
Mathieu, Alex-Ane. “Analyse protéomique de lignées cellulaires et de tissus de
cancer colorectal par spectrométrie de masse.” 2015. Web. 03 Mar 2021.
Vancouver:
Mathieu A. Analyse protéomique de lignées cellulaires et de tissus de
cancer colorectal par spectrométrie de masse. [Internet] [Masters thesis]. Université de Sherbrooke; 2015. [cited 2021 Mar 03].
Available from: http://www.collectionscanada.gc.ca/obj/thesescanada/vol2/QSHERU/TC-QSHERU-11143_7615.pdf ; http://savoirs.usherbrooke.ca/bitstream/11143/7615/4/Mathieu_Alex_Ane_MSc_2015.pdf.
Council of Science Editors:
Mathieu A. Analyse protéomique de lignées cellulaires et de tissus de
cancer colorectal par spectrométrie de masse. [Masters Thesis]. Université de Sherbrooke; 2015. Available from: http://www.collectionscanada.gc.ca/obj/thesescanada/vol2/QSHERU/TC-QSHERU-11143_7615.pdf ; http://savoirs.usherbrooke.ca/bitstream/11143/7615/4/Mathieu_Alex_Ane_MSc_2015.pdf
5.
Mathieu, Alex-Ane.
Analyse protéomique de lignées cellulaires et de tissus de cancer colorectal par spectrométrie de masse.: Proteomic analysis of colorectal cancer cell lines and tissues by mass spectrometry.
Degree: 2015, Université de Sherbrooke
URL: http://hdl.handle.net/11143/7615
► Abstract : Colorectal adenocarcinoma is one of the most important cancers in Canada in terms of mortality and morbidity. However, we still know very little…
(more)
▼ Abstract : Colorectal adenocarcinoma is one of the most important cancers in Canada in terms of mortality and morbidity. However, we still know very little on its molecular features. This study was divided into two sub-projects.
Sub-project A. At this time, no biomarker has the capacity of predicting a patient’s response to radiotherapy, which is a commonly used treatment of colorectal cancer. The goal of this section was to develop the methods to conduct a prospective or retrospective mass spectrometry study on the patient response to radiotherapy, through the use of human tissues. Mouse tissues and tissues of an anonymous patient were obtained in order to evaluate the feasibility of such a study. Different protein extraction techniques were evaluated. Total lysates and subcellular fractionations of fresh tissues allowed for a successful
analysis of the samples. The same was true of total lysates of fixed tissues. However, proteins extracted from cells isolated through laser capture microdissection were insufficient in numbers and their types were inconsistent with the expected results.
Sub-project B. In order to study the importance of proteins and cellular functions or pathways in different types of colorectal cancers. nine cell lines originating from colorectal carcinoma and from normal colon were fractionated according to four subcellular compartments and analysed through mass spectrometry. Until now, no research group had analysed, in a single study more than 5 cell lines as well as more than one subcellular compartment at once. Some cellular functions and canonical pathways were shown to be of high importance in many of the studied cell lines, such as the signalling through eIF2
pathway. Furthermore, the transcription regulators TP53, MYC and TGFB1were identified as potentially responsible for the observed proteomic characteristics.
In conclusion, this study allowed for a better understanding of important molecular caracteristics of colorectal cancer and allowed for the optimization of techniques that may serve in the discovery of new biomarkers relative to the use of radiotherapy as a treatment.
Advisors/Committee Members: Boisvert, François Michel (advisor).
Subjects/Keywords: Cancer colorectal; Spectrométrie de masse; Lignée cellulaire; Tissu; Ingenuity pathway analysis; Colorectal cancer; Mass spectrometry; Cell lines; Tissue; Ingenuity pathway analysis
…95
Figure 25 Préparation des données pour analyse par Ingenuity Pathway Analysis (IPA…
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mathieu, A. (2015). Analyse protéomique de lignées cellulaires et de tissus de cancer colorectal par spectrométrie de masse.: Proteomic analysis of colorectal cancer cell lines and tissues by mass spectrometry. (Masters Thesis). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/7615
Chicago Manual of Style (16th Edition):
Mathieu, Alex-Ane. “Analyse protéomique de lignées cellulaires et de tissus de cancer colorectal par spectrométrie de masse.: Proteomic analysis of colorectal cancer cell lines and tissues by mass spectrometry.” 2015. Masters Thesis, Université de Sherbrooke. Accessed March 03, 2021.
http://hdl.handle.net/11143/7615.
MLA Handbook (7th Edition):
Mathieu, Alex-Ane. “Analyse protéomique de lignées cellulaires et de tissus de cancer colorectal par spectrométrie de masse.: Proteomic analysis of colorectal cancer cell lines and tissues by mass spectrometry.” 2015. Web. 03 Mar 2021.
Vancouver:
Mathieu A. Analyse protéomique de lignées cellulaires et de tissus de cancer colorectal par spectrométrie de masse.: Proteomic analysis of colorectal cancer cell lines and tissues by mass spectrometry. [Internet] [Masters thesis]. Université de Sherbrooke; 2015. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/11143/7615.
Council of Science Editors:
Mathieu A. Analyse protéomique de lignées cellulaires et de tissus de cancer colorectal par spectrométrie de masse.: Proteomic analysis of colorectal cancer cell lines and tissues by mass spectrometry. [Masters Thesis]. Université de Sherbrooke; 2015. Available from: http://hdl.handle.net/11143/7615

Virginia Commonwealth University
6.
Wirth, Pamela.
THE PROGNOSTIC POTENTIAL OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND NUCLEAR FACTOR KAPPA B PATHWAYS AND ASSOCIATED THERAPEUTIC STRATEGIES IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK.
Degree: PhD, Health Related Sciences, 2010, Virginia Commonwealth University
URL: https://doi.org/10.25772/BCEY-2793
;
https://scholarscompass.vcu.edu/etd/2229
► Little is known about the signaling pathways that contribute to treatment response in advanced stage head and neck tumors. Increased expression of epidermal growth…
(more)
▼ Little is known about the signaling pathways that contribute to treatment response in advanced stage head and neck tumors. Increased expression of epidermal growth factor receptor (EGFR) and downstream pathways such as nuclear factor kappa B (NFκB) are implicated in aggressive tumor phenotypes and limited response to therapy. This study explored the rationale for combining the proteasome inhibitor bortezomib with the EGFR inhibitor gefitinib in a subset of head and neck squamous cell carcinomas with high EGFR gene amplification. Drug responses of gefitinib and bortezomib as single agents and in combination within head and neck squamous cell carcinoma cell lines were analyzed using MTS assays. The effects of gefitinib on the activation of EGFR and itsthree major downstream pathways, Akt, STAT3 and MAPK were determined by western blotting. The activation status of NFκB and the effects of bortezomib on the canonical
pathway were assessed by DNA binding assays. Resistance to lower doses of gefitinib was associated with elevated EGFR and activated Akt expression. Gefitinib was able to effectively inhibit activation of STAT3, Akt and MAPK in HNSCC to varying degrees depending on EGFR expression status. Bortezomib treatment inhibited TNFα –induced nuclear NFκB/RelA expression but demonstrated variability in levels of baseline nuclear NFκB/RelA expression between sensitive and resistant cell lines. Bortezomib effectively suppresses NFκB/RelA nuclear activation but demonstrates additional modes of cellular toxicity beyond the NFκB
pathway in sensitive cell lines. Further understanding of tumor response to the targeted inhibitors gefitinib and bortezomib may provide novel approaches in managing HNSCCs.
Advisors/Committee Members: Teresa Nadder.
Subjects/Keywords: head and neck squamous cell carcinoma; gefitinib; bortezomib; epidermal growth factor receptor; nuclear factor kappa B; MTS Assay; Ingenuity Pathway Analysis; Western blot; polymerase chain reaction; DNA binding assay; Medicine and Health Sciences
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wirth, P. (2010). THE PROGNOSTIC POTENTIAL OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND NUCLEAR FACTOR KAPPA B PATHWAYS AND ASSOCIATED THERAPEUTIC STRATEGIES IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/BCEY-2793 ; https://scholarscompass.vcu.edu/etd/2229
Chicago Manual of Style (16th Edition):
Wirth, Pamela. “THE PROGNOSTIC POTENTIAL OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND NUCLEAR FACTOR KAPPA B PATHWAYS AND ASSOCIATED THERAPEUTIC STRATEGIES IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK.” 2010. Doctoral Dissertation, Virginia Commonwealth University. Accessed March 03, 2021.
https://doi.org/10.25772/BCEY-2793 ; https://scholarscompass.vcu.edu/etd/2229.
MLA Handbook (7th Edition):
Wirth, Pamela. “THE PROGNOSTIC POTENTIAL OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND NUCLEAR FACTOR KAPPA B PATHWAYS AND ASSOCIATED THERAPEUTIC STRATEGIES IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK.” 2010. Web. 03 Mar 2021.
Vancouver:
Wirth P. THE PROGNOSTIC POTENTIAL OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND NUCLEAR FACTOR KAPPA B PATHWAYS AND ASSOCIATED THERAPEUTIC STRATEGIES IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2010. [cited 2021 Mar 03].
Available from: https://doi.org/10.25772/BCEY-2793 ; https://scholarscompass.vcu.edu/etd/2229.
Council of Science Editors:
Wirth P. THE PROGNOSTIC POTENTIAL OF THE EPIDERMAL GROWTH FACTOR RECEPTOR AND NUCLEAR FACTOR KAPPA B PATHWAYS AND ASSOCIATED THERAPEUTIC STRATEGIES IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK. [Doctoral Dissertation]. Virginia Commonwealth University; 2010. Available from: https://doi.org/10.25772/BCEY-2793 ; https://scholarscompass.vcu.edu/etd/2229

Lincoln University
7.
Chaiboonchoe, Amphun.
Identification of glucocorticoid-regulated genes and inferring their network focused on the glucocorticoid receptor in childhood leukaemia, based on microarray data and pathway databases.
Degree: 2010, Lincoln University
URL: http://hdl.handle.net/10182/2978
► Acute lymphoblastic leukaemia (ALL) has the highest mortality rate in childhood cancer. Glucocorticoids (GCs) have been used as chemotherapeutic drugs for children with ALL for…
(more)
▼ Acute lymphoblastic leukaemia (ALL) has the highest mortality rate in childhood cancer. Glucocorticoids (GCs) have been used as chemotherapeutic drugs for children with ALL for more than 50 years. GCs induce apoptosis in lymphoid cells. However, little is known about the molecular mechanism of GC-induced apoptosis and there are many controversial hypotheses about genes regulated by GCs and their gene networks. In particular, two main issues are investigated: (i) GC-regulated genes and (ii) the glucocorticoid receptor (GR) gene networks. Only few overlapping genes have been reported from previous studies. Moreover, GCs function by binding with their receptors. The underlying mechanisms of cell type specific GR gene networks are not well established.
The goal of this thesis is to understand the mechanism of the GC-induced apoptosis mechanism. The first part of this thesis presents an identification of GC-regulated genes. This study uses secondary microarray data, originating from prednisolone (glucocorticoid) treated childhood ALL samples (Schmidt et al., 2006) (B-linage and T-linage) that were collected before treatment and at six and twenty four hours after treatment. We replicate the authors’ original study and discover more probe sets including all the probe sets from that original study. This result shows the robustness of this data. Then, we extend the data analysis and propose new criteria based on differences between T- and B-ALL patients. The results reveal the proposed GC-regulated genes. These candidate genes are grouped in order to find similar expression patterns which lead to possible co-regulated genes, or similar function and sharing networks and pathways. Four emergent clustering methods are used: Self organising maps (SOM), Emergent self organising maps (ESOM), the Short Time series Expression Miner (STEM) and Fuzzy clustering by Local Approximation of MEmbership (FLAME). These genes are used in the following gene expression analysis step.
The second part of this thesis focuses on inferring gene networks of GC-regulated genes and GR. There are many tools available for inferring gene networks including mathematical modelling and statistical methods. Each tool has its own advantages and disadvantages. For a modelling method, how do we know that the model represents the true relationship or interaction among genes? The need to verify results from modelling still exists. Prior knowledge has been used for this purpose. In this study, we use literature knowledge-based network tools, mainly the Ingenuity Pathway Analysis software (IPA) to elucidate gene networks. First, we illustrated gene networks at three time intervals and identified the prominent genes during those time points. Second, we further elucidated GR gene networks using gene lists from STEM. Third, we investigated the behaviour of selected known genes from the apoptosis, p53 and NFB pathways and inferred gene networks from the selected genes. Fourth, we inferred GR gene networks using the same gene list from previous studies (Phillip et…
Subjects/Keywords: self organising maps (SOM); childhood leukaemia; glucocorticoids; gene expression; pathway databases; apoptosis; BiblioSphere Pathway Edition; DNA microarray; emergent self organising maps; fuzzy clustering by Local Approximation of MEmbership; glucocorticoid receptor; Ingenuity Pathway Analysis software; prednisolone; short time series clustering; Short Time series Expression Miner
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chaiboonchoe, A. (2010). Identification of glucocorticoid-regulated genes and inferring their network focused on the glucocorticoid receptor in childhood leukaemia, based on microarray data and pathway databases. (Thesis). Lincoln University. Retrieved from http://hdl.handle.net/10182/2978
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chaiboonchoe, Amphun. “Identification of glucocorticoid-regulated genes and inferring their network focused on the glucocorticoid receptor in childhood leukaemia, based on microarray data and pathway databases.” 2010. Thesis, Lincoln University. Accessed March 03, 2021.
http://hdl.handle.net/10182/2978.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chaiboonchoe, Amphun. “Identification of glucocorticoid-regulated genes and inferring their network focused on the glucocorticoid receptor in childhood leukaemia, based on microarray data and pathway databases.” 2010. Web. 03 Mar 2021.
Vancouver:
Chaiboonchoe A. Identification of glucocorticoid-regulated genes and inferring their network focused on the glucocorticoid receptor in childhood leukaemia, based on microarray data and pathway databases. [Internet] [Thesis]. Lincoln University; 2010. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10182/2978.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chaiboonchoe A. Identification of glucocorticoid-regulated genes and inferring their network focused on the glucocorticoid receptor in childhood leukaemia, based on microarray data and pathway databases. [Thesis]. Lincoln University; 2010. Available from: http://hdl.handle.net/10182/2978
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Khan, Muhammad.
Effect of Maternal Age on Transcriptome of Granulosa Cells from Bovine Dominant Follicles.
Degree: 2014, University of Saskatchewan
URL: http://hdl.handle.net/10388/ETD-2014-01-1364
► Advanced maternal age has been shown to influence follicular and luteal dynamics in bovine ovary resulting in reduced fertility. The overall objective of the four…
(more)
▼ Advanced maternal age has been shown to influence follicular and luteal dynamics in bovine ovary resulting in reduced fertility. The overall objective of the four studies presented in this thesis is to identify the maternal age-associated transcriptional changes in granulosa cells of the dominant follicles during follicle development.
In the first study, mRNA expression levels of housekeeping genes were measured by real–time quantitative PCR (RT-qPCR) in granulosa cells of dominant follicles and FSH-stimulated follicles to select and validate suitable reference genes for relative gene expression analyses during maternal and follicular aging. Stability of six reference genes (GAPDH, ACTB, EIF2B2, UBE2D2, SF3A1 and RNF20) was analyzed using GeNorm, DeltaCT and NormFinder programs and comprehensive ranking order was determined based on these programs. Geometric mean of multiple genes (UBE2D2, EIF2B2, GAPDH and SF3A1) was more appropriate reference control than individual genes for the comparison of relative gene expression among dominant and FSH-stimulated follicles during maternal and/or follicular aging studies.
In the second study, maternal age-associated changes in the transcriptome of granulosa cells recovered at the time of selection of the dominant follicle from aged (n=3) and young cows (n=3) were determined by EmbryoGENE bovine oligo-microarrays (EMBV3, Agilent Technology). The mRNA expression of five transcripts (CYP19A1, PCNA, GJA1, TPM2, and VNN1) was confirmed in a different set of granulosa cell samples by RT-qPCR to validate microarray data. A total of 169 genes/isoforms were differentially expressed (≥ 2-fold-change; P ≤ 0.05) in aged cows vs. young cows. These transcripts revealed inefficient 1) control of gonadotropins, and gonadotropin-induced changes in the cytoskeleton and extracellular matrix, 2) lipid metabolism and steroidogenesis 3) cell proliferation, cell cycle control and intercellular communication, and 4) higher oxidative stress responses in aged cows vs. young cows.
In the third study, changes in the transcriptome of granulosa cells of the preovulatory follicle 24 h after LH treatment from aged (n= 3) and young (n=3) were determined. A total of 1340 genes were expressed differentially (≥ 2-fold change; P ≤ 0.05) in aged cows vs. young cows. The mRNA expression of five transcripts (RGS2, PTGS2, TNFAIP6, VNN1, NR5A2 and GADD45B) was confirmed in a different set of granulosa cell samples to validate microarray data. These transcripts were related to delayed 1) response to LH treatment 2) cellular differentiation and luteinization and 3) progesterone synthesis. Intra-follicle levels of progesterone were lower (P < 0.05) in aged cows compared to young and mid-aged cows.
The fourth study compared the aged-associated changes in the transcriptome of granulosa cells during follicle development from the time of dominant follicle selection to preovulatory stage (24 h after LH). In comparison to young cows, aged cows expressed fewer differentially expressed genes/isoforms (1206 vs. 2260, respectively)…
Advisors/Committee Members: Singh, Jaswant, Adams, Gregg P., Sirard, Marc A., Misra, Vikram, Anzar, Muhammad.
Subjects/Keywords: Maternal age; Granulosa cells; Dominant follicle at selection; Preovulatory follicle; Reference genes; Microarrays; RT-qPCR; Bovine; Luteinizing hormone; Ovariectomy; Follicular aspiration; Transcriptome analysis; Ingenuity Pathway Analysis; Upstream regulators; Estradiol; Progesterone; Follicular fluid; Ultrasonography; Ovulation
…120
Table 5.3 Upstream regulators predicted by Ingenuity pathway analysis (IPA)… …2, TP53) were identified by the Ingenuity Pathway Analysis software (Table
4… …Ingenuity Pathway Analysis software. ................................. 92
Figure 4.5 Expression of… …identified by the Ingenuity Pathway Analysis software (Table
5.3) and were placed in the… …generated by
Ingenuity Pathway Analysis software…
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Khan, M. (2014). Effect of Maternal Age on Transcriptome of Granulosa Cells from Bovine Dominant Follicles. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2014-01-1364
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Khan, Muhammad. “Effect of Maternal Age on Transcriptome of Granulosa Cells from Bovine Dominant Follicles.” 2014. Thesis, University of Saskatchewan. Accessed March 03, 2021.
http://hdl.handle.net/10388/ETD-2014-01-1364.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Khan, Muhammad. “Effect of Maternal Age on Transcriptome of Granulosa Cells from Bovine Dominant Follicles.” 2014. Web. 03 Mar 2021.
Vancouver:
Khan M. Effect of Maternal Age on Transcriptome of Granulosa Cells from Bovine Dominant Follicles. [Internet] [Thesis]. University of Saskatchewan; 2014. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10388/ETD-2014-01-1364.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Khan M. Effect of Maternal Age on Transcriptome of Granulosa Cells from Bovine Dominant Follicles. [Thesis]. University of Saskatchewan; 2014. Available from: http://hdl.handle.net/10388/ETD-2014-01-1364
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat Pompeu Fabra
9.
Guidi, Mònica.
Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3).
Degree: Departament de Ciències Experimentals i de la Salut, 2009, Universitat Pompeu Fabra
URL: http://hdl.handle.net/10803/7114
► Las neurotrofinas y sus receptores constituyen una familia de factores cruciales para el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su función principalmente a…
(more)
▼ Las neurotrofinas y sus receptores constituyen una familia de factores cruciales para el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su función principalmente a través de una unión de gran afinidad al receptor NTRK3, del cual se conocen dos isoformas principales, una larga de 150KDa con actividad de tipo tirosina kinasa y una truncada de 50KDa sin dicha actividad. Estas dos isoformas no comparten la misma región 3'UTR, lo que sugiere la existencia de una regulación postranscripcional diferente. En el presente trabajo se ha explorado como los microRNAs intervienen en la regulación de NTRK3, demostrando que las dos isoformas son reguladas por diferentes miRNAs. Se han analizado las consecuencias fisiológicas de la sobrexpresión de dichos microRNAs utilizando células de neuroblastoma. Finalmente, se ha estudiado la posible implicación del microRNA miR-124 en el control del splicing alternativo de NTRK3 a través de la regulación de represor de splicing PTBP1.
Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Espinosa Parrilla, Yolanda (director), Estivill, Xavier, 1955- (director).
Subjects/Keywords: RISC complex; retinoic acid; renilla luciferase; real-time quantitative PCR; PTBP1; pri-miRNA; pre-miRNA; post-transcriptional regulation; piRNA; PicTar; pGL4.13; PCR; P-body; p75NTR; overexpression; NTRK3; NTRK2; NTRK1; non-coding RNAs; NGF; neurotrophin; neurotrophic signaling; neuronal differentiation; neurodevelopment; neuroblastoma; nervous system; mRNA; miRNA target prediction; miRNA profiling; miRNA mimic; miRNA microarray; miRNA inhibitor; miRanda; microRNA; microarray; luciferase assay; Ingenuity Pathway Analysis (IPA); heLa cells; gene silencing; gene regulation; full-length isoform (FL-NTRK3); firefly luciferase; ERK; disease; dicer; cancer development; BDNF; argonaute; alternative splicing; 3'UTR; RNAhybrid; RT-PCR; SH-SY5Y cells; siRNA; standard error; synaptic plasticity; target validation; TargetScan; transfection; translational repression; TrkA; TrkB; TrkC; truncated isoform (TR-NTRK3); tyrosine kinase (TK); western blot; 577
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Guidi, M. (2009). Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3). (Thesis). Universitat Pompeu Fabra. Retrieved from http://hdl.handle.net/10803/7114
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Guidi, Mònica. “Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3).” 2009. Thesis, Universitat Pompeu Fabra. Accessed March 03, 2021.
http://hdl.handle.net/10803/7114.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Guidi, Mònica. “Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3).” 2009. Web. 03 Mar 2021.
Vancouver:
Guidi M. Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3). [Internet] [Thesis]. Universitat Pompeu Fabra; 2009. [cited 2021 Mar 03].
Available from: http://hdl.handle.net/10803/7114.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Guidi M. Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3). [Thesis]. Universitat Pompeu Fabra; 2009. Available from: http://hdl.handle.net/10803/7114
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
.