You searched for subject:(Lung Cancer).
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Harvard University
1.
Li, Richard.
Venous Thromboembolism Risk in Patients With Locally Advanced Non-Small Cell Lung Cancer.
Degree: Doctor of Medicine, 2016, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:40620276 
► Background: Patients with non-small cell lung cancer (NSCLC) are known to be at high risk for venous thromboembolism (VTE), but previous studies have not specifically…
(more)
▼ Background: Patients with non-small cell lung cancer (NSCLC) are known to be at high risk for venous thromboembolism (VTE), but previous studies have not specifically analyzed locally advanced disease. We performed a retrospective VTE risks analysis in a cohort of locally advanced NSCLC treated with definitive radiation.
Methods: The cohort consisted of 629 patients with stage II-III NSCLC treated at a single institution from January 2003 to December 2012. All patients received definitive therapy with curative intent. Fine and Gray’s competing-risks regression model, accounting for death and distant metastasis as competing risks, was used to identify significant predictors of VTE risk, and cumulative incidence estimates were generated using the competing-risks model.
Results: At a median follow-up of 31 months, 127 patients developed a VTE, with 80% of events occurring in the first year after treatment initiation. 1-year and 3-year overall cumulative incidence estimates were 13.5% and 15.4%, respectively. On univariate analysis, stage IIIB and N3 nodal disease were associated with increased VTE risk. In the final multivariate model, N3 nodal disease was associated with increased VTE risk (Hazard ratio 1.64; 95% CI 1.06-2.54; p=0.027).
Conclusions: Patients with locally advanced NSCLC are at high risk for VTE, especially in the first year after treatment initiation, with a 1-year cumulative incidence of 13.5%. N3 nodal staging was associated with significantly higher VTE risk compared to N0-N2 staging.
Scholarly Project
Subjects/Keywords: lung cancer; thromboembolism
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APA (6th Edition):
Li, R. (2016). Venous Thromboembolism Risk in Patients With Locally Advanced Non-Small Cell Lung Cancer. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:40620276
Chicago Manual of Style (16th Edition):
Li, Richard. “Venous Thromboembolism Risk in Patients With Locally Advanced Non-Small Cell Lung Cancer.” 2016. Doctoral Dissertation, Harvard University. Accessed January 27, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:40620276.
MLA Handbook (7th Edition):
Li, Richard. “Venous Thromboembolism Risk in Patients With Locally Advanced Non-Small Cell Lung Cancer.” 2016. Web. 27 Jan 2021.
Vancouver:
Li R. Venous Thromboembolism Risk in Patients With Locally Advanced Non-Small Cell Lung Cancer. [Internet] [Doctoral dissertation]. Harvard University; 2016. [cited 2021 Jan 27].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:40620276.
Council of Science Editors:
Li R. Venous Thromboembolism Risk in Patients With Locally Advanced Non-Small Cell Lung Cancer. [Doctoral Dissertation]. Harvard University; 2016. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:40620276
University of Dundee
2.
Robertson, Holly.
Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression.
Degree: PhD, 2019, University of Dundee
URL: https://discovery.dundee.ac.uk/en/studentTheses/4a7f87db-89f1-4bc4-b273-1bd7eb72ab0e
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775364
► Lung cancer is the leading cause of cancer related mortality worldwide and since the discovery of the important role that NRF2 plays in regulating the…
(more)
▼ Lung cancer is the leading cause of cancer related mortality worldwide and since the discovery of the important role that NRF2 plays in regulating the expression of phase II drug metabolism genes, NRF2 has been a highly studied therapeutic target. NRF2 signalling is often elevated in lung cancer due to mutations in NFE2L2, the gene that encodes NRF2; and KEAP1, the cytoplasmic regulator of NRF2. Since it became established that elevated NRF2 signalling provides a beneficial role to the tumour through enhancing proliferation, enabling survival in highly oxidative conditions and enhancing resistance to chemotherapeutic drugs; many groups have focussed on understanding KEAP1-independent forms of NRF2 regulation. It is now widely accepted that GSK-3 phosphorylation of the Neh6 domain of NRF2 is fundamental for SCFβ-TrCP-mediated degradation of the transcription factor. Previous work by other groups has indicated a potential role for a priming kinase to pre-phosphorylate the Neh6 domain and subsequently enhance GSK-3 mediated phosphorylation and resulting 26S proteasomal degradation. In the first results chapter of this thesis it was demonstrated using the DYRK family of isoenzymes that the presence of a priming kinase enhances GSK-3 phosphorylation and stimulates NRF2 degradation. Also, it has been shown that DYRK family members carry out priming of NRF2 through phosphorylating Ser-347, which enhances subsequent phosphorylation of Ser-342 and Ser-338 by GSK-3; regulating both NRF2 activity and stability. Additionally, it was shown that altering the phosphorylation status of Ser-347 impacts cell proliferation and chemo-sensitivity to platinum-based compounds. The ability of other kinases to phosphorylate the Neh6 domain was also revealed. In the second results chapter of this thesis a bioinformatics style approach was utilized to analyse the impact of mutations in KEAP1, NFE2L2 and CUL3; in terms of their effect on NRF2 activity using the expression of NRF2-target genes as a read out. The following points were highlighted from this analysis; (1) KEAP1 mutations are more prevalent than NFE2L2 and CUL3 mutations in both lung cancer cell lines and tumours; (2) KEAP1 and NFE2L2 mutations vary in there associated zygosity's, with KEAP1 mutations being predominantly homozygous and NFE2L2 mutations being predominantly heterozygous; (3) mutations in KEAP1 coexist with mutations in KRAS whereas, mutations in NFE2L2 co-exist with mutations in TP53 and (4) lung cancer cell lines and tumours harbouring mutations in KEAP1 have greater expression of NRF2-target genes than those harbouring either NFE2L2 or CUL3 mutations. In the third and final results chapter, both a panel of commercial cell lines and an in-house generated CRISPR/Cas9 panel of cell lines have been shown in multiple experiments to validate the bioinformatics findings of the previous chapter. Also, in this chapter it was identified that KEAP1 mutant cells are more reliant on the glutathione biosynthesis pathway for survival and therefore more sensitive to alterations in…
Subjects/Keywords: NRF2; Lung Cancer
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APA (6th Edition):
Robertson, H. (2019). Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression. (Doctoral Dissertation). University of Dundee. Retrieved from https://discovery.dundee.ac.uk/en/studentTheses/4a7f87db-89f1-4bc4-b273-1bd7eb72ab0e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775364
Chicago Manual of Style (16th Edition):
Robertson, Holly. “Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression.” 2019. Doctoral Dissertation, University of Dundee. Accessed January 27, 2021.
https://discovery.dundee.ac.uk/en/studentTheses/4a7f87db-89f1-4bc4-b273-1bd7eb72ab0e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775364.
MLA Handbook (7th Edition):
Robertson, Holly. “Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression.” 2019. Web. 27 Jan 2021.
Vancouver:
Robertson H. Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression. [Internet] [Doctoral dissertation]. University of Dundee; 2019. [cited 2021 Jan 27].
Available from: https://discovery.dundee.ac.uk/en/studentTheses/4a7f87db-89f1-4bc4-b273-1bd7eb72ab0e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775364.
Council of Science Editors:
Robertson H. Mechanisms of repression of the transcription factor NRF2 by KEAP1- and B-TrCP-dependent ubiquitin ligases and how the dysregulation of NRF2 contributes to lung cancer progression. [Doctoral Dissertation]. University of Dundee; 2019. Available from: https://discovery.dundee.ac.uk/en/studentTheses/4a7f87db-89f1-4bc4-b273-1bd7eb72ab0e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775364
University of New South Wales
3.
Wong, Sze Wing (Alice).
Functions of S100A8 in lung cancer.
Degree: Medical Sciences, 2018, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/60230
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51254/SOURCE02?view=true
► S100A8 is an anti-inflammatory oxidant scavenger protein that induces IL-10 in airway epithelial cells in normal lungs following inhalation. These mechanisms contribute to its ability…
(more)
▼ S100A8 is an anti-inflammatory oxidant scavenger protein that induces IL-10 in airway epithelial cells in normal lungs following inhalation. These mechanisms contribute to its ability to attenuate endotoxin-induced acute lung injury by suppressing proinflammatory mediator induction. Sustained chronic inflammation promotes activation of myeloid-derived suppressor cells (MDSC) to reduce T cell surveillance by producing toxic reactive oxygen species and nitric oxide, and depleting the essential nutrient, arginine. MDSC accumulation facilitates tumour progression and is associated with reduced survival in lung cancer. S100A8 is upregulated in human lung cancer and the associations of S100 proteins with MDSC suggest a potential immunomodulatory role. We proposed that the anti-inflammatory and antioxidative properties of S100A8 improved outcomes in lung cancer. Remarkably, repeated S100A8 inhalation prolonged survival by up to 40% in mice implanted with orthotopic lung cancer (from 19±1 to 27±1 days). Tumour-bearing mice treated with S100A8 harvested at earlier time points were compared with vehicle-treated controls to identify potential changes in the microenvironment. At mid-point of survival, S100A8 significantly suppressed key cytokines that promote MDSC expansion and activation, with concomitant reduced MDSC numbers in lungs and spleen. Importantly, S100A8 also increased CD4 and NK-T cell numbers in these organs, suppressed nitrite levels and selectively enhanced activities of key antioxidant enzymes in lungs. S100A8 also upregulated thioredoxin reductase activity in lungs 3 days post-inhalation. Results suggest that S100A8 created a favourable microenvironment for effector T cell recruitment and function. Lung cancer is generally associated with poor prognosis and with limited treatment options, and S100A8 may enhance immunoprotection. Its delivery in combination with currently-available treatments may improve clinical outcomes.
Subjects/Keywords: Lung cancer; S100A8
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APA (6th Edition):
Wong, S. W. (. (2018). Functions of S100A8 in lung cancer. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/60230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51254/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Wong, Sze Wing (Alice). “Functions of S100A8 in lung cancer.” 2018. Doctoral Dissertation, University of New South Wales. Accessed January 27, 2021.
http://handle.unsw.edu.au/1959.4/60230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51254/SOURCE02?view=true.
MLA Handbook (7th Edition):
Wong, Sze Wing (Alice). “Functions of S100A8 in lung cancer.” 2018. Web. 27 Jan 2021.
Vancouver:
Wong SW(. Functions of S100A8 in lung cancer. [Internet] [Doctoral dissertation]. University of New South Wales; 2018. [cited 2021 Jan 27].
Available from: http://handle.unsw.edu.au/1959.4/60230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51254/SOURCE02?view=true.
Council of Science Editors:
Wong SW(. Functions of S100A8 in lung cancer. [Doctoral Dissertation]. University of New South Wales; 2018. Available from: http://handle.unsw.edu.au/1959.4/60230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51254/SOURCE02?view=true
University of Southern California
4.
Selamat, Suhaida Adura.
DNA methylation changes in the development of lung
adenocarcinoma.
Degree: PhD, Genetic, Molecular and Cellular Biology, 2012, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/2645/rec/2069
► Lung cancer accounted for 13% of total cancer cases and 18% of cancer deaths globally in 2008. The combination of increasing smoking prevalence in many…
(more)
▼ Lung cancer accounted for 13% of total
cancer cases
and 18% of
cancer deaths globally in 2008. The combination of
increasing smoking prevalence in many developing countries and a
long latency period predicts that
lung cancer will remain a major
world health problem for decades to come. This work focuses on DNA
methylation in
lung adenocarcinoma, a subtype of
lung cancer that
is the most prevalent in the United States, as well as the most
common amongst women and non-smokers. We built on previously
identified DNA methylation early detection markers by delineating
the timing of these changes in preneoplastic lesions. We then used
genome-scale DNA methylation profiling to identify novel potential
blood-based non-small cell
lung cancer biomarkers, and integrated
DNA methylation information with gene expression data to identify
DNA methylation changes that may lead to functional consequences in
the development of
cancer. Additionally, we identified a DNA
methylation based subgroup of
lung adenocarcinoma that is
associated with KRAS mutations and smoking status, as well as
explored the use of paraffin-embedded tissues to facilitate larger
genome-scale DNA methylation studies. Our findings provide insights
into the roles that DNA methylation may play in the development of
lung adenocarcinoma, as well as potential DNA methylation markers
for the early detection or risk assessment of the
disease.
Advisors/Committee Members: Laird-Offringa, Ite A. (Committee Chair), Siegmund, Kimberly (Committee Member), Borok, Zea (Committee Member).
Subjects/Keywords: DNA methylation; lung adenocarcinoma; lung cancer; epigenetics
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APA (6th Edition):
Selamat, S. A. (2012). DNA methylation changes in the development of lung
adenocarcinoma. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/2645/rec/2069
Chicago Manual of Style (16th Edition):
Selamat, Suhaida Adura. “DNA methylation changes in the development of lung
adenocarcinoma.” 2012. Doctoral Dissertation, University of Southern California. Accessed January 27, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/2645/rec/2069.
MLA Handbook (7th Edition):
Selamat, Suhaida Adura. “DNA methylation changes in the development of lung
adenocarcinoma.” 2012. Web. 27 Jan 2021.
Vancouver:
Selamat SA. DNA methylation changes in the development of lung
adenocarcinoma. [Internet] [Doctoral dissertation]. University of Southern California; 2012. [cited 2021 Jan 27].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/2645/rec/2069.
Council of Science Editors:
Selamat SA. DNA methylation changes in the development of lung
adenocarcinoma. [Doctoral Dissertation]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/2645/rec/2069
Universiteit Utrecht
5.
Breeveld, A.R.
Shape of the exposure response relation for crystalline silica and risk of lung cancer.
Degree: 2011, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/209135
► Crystalline silica exposure mostly occurs in occupational settings such as mining, construction, several industries (e.g. foundries) and agriculture. Occupational exposure to silica dust is known…
(more)
▼ Crystalline silica exposure mostly occurs in occupational settings such as mining, construction, several industries (e.g. foundries) and agriculture. Occupational exposure to silica dust is known to be related to several non-malignant respiratory health effects. In addition respirable crystalline silica has been classified as malignant by the International Agency for Research on
Cancer (IARC) since 1997. However, conflicting data has fueled a debate against this classification for the past decade. In the presented study quantitative data on the exposure response relationship between occupational crystalline silica exposure and risk of
lung cancer was evaluated by applying a formal meta regression. Data was collected from studies used in a meta-analysis performed by Lacasse and co-workers in 2009 and more recent studies which reported quantitatively on the relation between crystalline silica and
lung cancer. The main aim was to shed light on the actual shape of the exposure response relation for respirable crystalline silica and
lung cancer. Both a linear and a natural spline model were fitted to the data. The natural spline model fitted the data better and showed a small, but statistically significant (p =0.04) increase in
lung cancer risk resulting from increasing crystalline silica exposure. This increase however was only observed at relatively low levels of cumulative exposure to crystalline silica.
Advisors/Committee Members: Kromhout, H.
Subjects/Keywords: crystalline silica; lung cancer
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APA (6th Edition):
Breeveld, A. R. (2011). Shape of the exposure response relation for crystalline silica and risk of lung cancer. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/209135
Chicago Manual of Style (16th Edition):
Breeveld, A R. “Shape of the exposure response relation for crystalline silica and risk of lung cancer.” 2011. Masters Thesis, Universiteit Utrecht. Accessed January 27, 2021.
http://dspace.library.uu.nl:8080/handle/1874/209135.
MLA Handbook (7th Edition):
Breeveld, A R. “Shape of the exposure response relation for crystalline silica and risk of lung cancer.” 2011. Web. 27 Jan 2021.
Vancouver:
Breeveld AR. Shape of the exposure response relation for crystalline silica and risk of lung cancer. [Internet] [Masters thesis]. Universiteit Utrecht; 2011. [cited 2021 Jan 27].
Available from: http://dspace.library.uu.nl:8080/handle/1874/209135.
Council of Science Editors:
Breeveld AR. Shape of the exposure response relation for crystalline silica and risk of lung cancer. [Masters Thesis]. Universiteit Utrecht; 2011. Available from: http://dspace.library.uu.nl:8080/handle/1874/209135
University of Alberta
6.
Al-Hallak, MHD Kamal.
Inhalable nanoparticles in lung cancer treatment; efficacy,
safety, distribution and nanoparticle-macrophage
interactions.
Degree: PhD, Faculty of Pharmacy and Pharmaceutical
Sciences, 2012, University of Alberta
URL: https://era.library.ualberta.ca/files/mk61rj53p
► In 2002, lung cancer was responsible for 17.6% of the total worldwide deaths from cancer. Beyond the three traditional forms of cancer treatment, surgery, radiation…
(more)
▼ In 2002, lung cancer was responsible for 17.6% of the
total worldwide deaths from cancer. Beyond the three traditional
forms of cancer treatment, surgery, radiation therapy, and
chemotherapy, targeted drug delivery therapy has shown to be a
potential treatment option. The design of a successful delivery
system requires consideration of many factors, some of which
include (i) the location and main organ(s) affected; (ii) the
complexity of the associated physiological changes; (iii) the
changes in receptor expression in cancerous cells; (iv) the
physiochemical properties of the delivery system; (v) the
interactions between the cancerous cells and other adjuvant cells,
such as macrophages, with the delivery system; and (vi) the safety
and tolerability of the delivery system. Considering the above
factors of a successful delivery system, the aim of the present
work was to design an innovative delivery system for lung cancer
treatment incorporating inhalable nanoparticles (NP). To achieve
this goal, several objectives were developed: (i) to investigate
the interactions of different NP formulations with macrophages and
the resulting effects on the behavior of macrophages; (ii) to
assess and correlate the pulmonary toxicity of inhalable NPs using
in vivo and in vitro methods; (iii) to develop a method to assess
in real-time the effect of the formulation modifications on the
uptake by macrophages of NPs; (iv) to assess the in vivo efficacy
of an innovative formulation of effervescent inhalable NPs, thus
actively releasing NPs; and finally, (v) to investigate the
distribution of effervescent inhalable NPs after pulmonary
delivery. Our results demonstrate that after exposure to NPs,
macrophages undergo cellular changes to gain the ability to produce
Th1 cytokines that are able to affect the viability of cancerous
cells. The tolerability of inhalable NPs was related mainly to the
additives used in the NP formulation. There was a good correlation
between the in vivo and in vitro results. Effervescent inhalable
NPs proved to be an effective and tolerable treatment for lung
cancer treatment. Whole body autoradiography showed that inhalable
NPs were able to achieve deep lung deposition and become
distributed in time over the whole lung with some extra-pulmonary
distribution.
Subjects/Keywords: inhalable nanoparticles; Lung cancer; Macrophages
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APA ·
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Manager
APA (6th Edition):
Al-Hallak, M. K. (2012). Inhalable nanoparticles in lung cancer treatment; efficacy,
safety, distribution and nanoparticle-macrophage
interactions. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/mk61rj53p
Chicago Manual of Style (16th Edition):
Al-Hallak, MHD Kamal. “Inhalable nanoparticles in lung cancer treatment; efficacy,
safety, distribution and nanoparticle-macrophage
interactions.” 2012. Doctoral Dissertation, University of Alberta. Accessed January 27, 2021.
https://era.library.ualberta.ca/files/mk61rj53p.
MLA Handbook (7th Edition):
Al-Hallak, MHD Kamal. “Inhalable nanoparticles in lung cancer treatment; efficacy,
safety, distribution and nanoparticle-macrophage
interactions.” 2012. Web. 27 Jan 2021.
Vancouver:
Al-Hallak MK. Inhalable nanoparticles in lung cancer treatment; efficacy,
safety, distribution and nanoparticle-macrophage
interactions. [Internet] [Doctoral dissertation]. University of Alberta; 2012. [cited 2021 Jan 27].
Available from: https://era.library.ualberta.ca/files/mk61rj53p.
Council of Science Editors:
Al-Hallak MK. Inhalable nanoparticles in lung cancer treatment; efficacy,
safety, distribution and nanoparticle-macrophage
interactions. [Doctoral Dissertation]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/mk61rj53p
Cornell University
7.
Jirapatnakul, Artit.
Computer Methods For Pulmonary Nodule Characterization From Ct Images.
Degree: M.S., Electrical Engineering, Electrical Engineering, 2011, Cornell University
URL: http://hdl.handle.net/1813/29192
► Computed tomography (CT) scans provide radiologists a non-invasive method of imaging internal structures of the body. Although CT scans have enabled the earlier detection of…
(more)
▼ Computed tomography (CT) scans provide radiologists a non-invasive method of imaging internal structures of the body. Although CT scans have enabled the earlier detection of suspicious nodules, these nodules are often small and difficult to accurately classify for radiologists. An automated system was developed to classify a pulmonary nodule based on image features extracted from a single CT scan. Several critical issues related to performance evaluation of such systems were also examined. The image features considered in the system were: statistics from the density distribution, shape, curvature, and boundary features. The shape and density features were computed through moment analysis of the segmented nodule. Local curvature was computed from a triangle-tessellated surface of the nodule; the statistics of the distribution of curvatures were used as features in the system. Finally, the boundary of the nodule was examined to quantify the transition region between the nodule and
lung parenchyma. This was accomplished by combining the grayscale information and 3D model to measure the gradient on the surface of the nodule. These methods resulted in a total of 43 features. For compari- son, 2D features were computed for the density and shape features, resulting in 26 features. Four feature classification schemes were evaluated: logistic regression, k-nearest-neighbors, distance-weighted nearest-neighbors, and support vector machines (SVM). These features and classifiers were validated on a large dataset of 259 nodules. The best performance, an area under the ROC curve (AUC) of 0.702, was achieved using 3D features and the logistic regression classifier. A major consideration when evaluating a nodule classification system is whether the system presents an improvement over a baseline performance. Since the majority of large nodules in many datasets are malignant, the impact of nodule size on the performance of the classification system was examined. This was accomplished by comparing the performance of the system with feature sets that included sizedependent features to feature sets that excluded those features.The performance of size alone, estimated using a size-threshold classifier, was an AUC of 0.653. For the SVM classifier, removing size-dependent features reduced the performance from an AUC of 0.69 to 0.61. To approximate the performance that might be obtained on a dataset without a size bias, a subset of cases was selected where the benign and malignant nodules were of similar sizes. On this subset, size was not a very powerful feature with an AUC of 0.507, and features that were not dependent on size performed better than size-dependent features for SVM, with an AUC of 0.63 compared to 0.52. While other methods have been proposed for performing nodule classification, this is the first study to comprehensively look at the performance impact from datasets with nodules that exhibit a bias in size.
Advisors/Committee Members: Reeves, Anthony P (chair), Doerschuk, Peter (committee member).
Subjects/Keywords: pulmonary nodule; characterization; lung cancer
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APA (6th Edition):
Jirapatnakul, A. (2011). Computer Methods For Pulmonary Nodule Characterization From Ct Images. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/29192
Chicago Manual of Style (16th Edition):
Jirapatnakul, Artit. “Computer Methods For Pulmonary Nodule Characterization From Ct Images.” 2011. Masters Thesis, Cornell University. Accessed January 27, 2021.
http://hdl.handle.net/1813/29192.
MLA Handbook (7th Edition):
Jirapatnakul, Artit. “Computer Methods For Pulmonary Nodule Characterization From Ct Images.” 2011. Web. 27 Jan 2021.
Vancouver:
Jirapatnakul A. Computer Methods For Pulmonary Nodule Characterization From Ct Images. [Internet] [Masters thesis]. Cornell University; 2011. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1813/29192.
Council of Science Editors:
Jirapatnakul A. Computer Methods For Pulmonary Nodule Characterization From Ct Images. [Masters Thesis]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/29192
Vanderbilt University
8.
Samanta, Debangshu.
Long-term smoking-mediated downregulation of Smad3 induces tumorigenicity and carboplatin resistance in non-small cell lung cancer.
Degree: PhD, Cancer Biology, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/12131
► Inactivating mutations in TGF-©¬ receptors and Smad signal transducers that contribute to resistance to TGF-©¬, are associated with only very small number of NSCLC. The…
(more)
▼ Inactivating mutations in TGF-©¬ receptors and Smad signal transducers that contribute to resistance to TGF-©¬, are associated with only very small number of NSCLC. The Smad dependent pathway is involved in the tumor suppressive functions of TGF-¥â. Epidemiological studies have demonstrated that most cases of
lung cancer (85-90%) are directly attributable to cigarette smoking. However, nothing is known how smoking is involved in inhibiting tumor suppressor functions of TGF-©¬ and whether or how the chemo resistance of platinum-based drugs seen in
lung cancer patients who are smokers is dependent on this pathway. To address this issue,
lung adenocarcinoma A549 and immortalized bronchial epithelial HPL1A cells were chronically treated (300 days) with cigarette smoke condensate (CSC) and Dimethyl sulphoxide (DMSO, as a control) to mimic the conditions of long-term cigarette smoking. Prolonged exposure of these cells to CSC resulted in decreased Smad-mediated TGF-¥â signaling due to reduced expression of Smad3 both in the protein and mRNA level. The decrease in Smad3 is due to histone deacetylation. Long-term CSC treatment reduced apoptosis, increased cell viability, decreased TGF-¥â-mediated growth inhibition, and enhanced tumorigenicity both in vitro and in vivo. Re-expression of Smad3 in the long-term CSC treated cells reversed the cancerous phenotypes observed due to long-term CSC treatment. Looking further into public databases revealed that the expression of Smad3 is lower in
lung tumors of current smokers compared to that observed in never-smokers. The long-term CSC treatment also rendered the cells resistant to platinum-based chemotherapy; by up regulating Bcl2. Blocking the effect of Bcl2 both by small molecule inhibitor ABT-737 and siRNA approaches re-sensitized the cells to platinum-based chemotherapy. The re-expression of exogenous Smad3 in the long-term CSC treated cells, decreased the Bcl2 levels and re-sensitized the cells to platinum-based chemotherapy. Thus, Smad3 controls the expression of Bcl2 and sensitivity to platinum based drugs in our model system. Collectively, these data provide evidence that cigarette smoking promotes tumorigenicity and makes the cells resistant to platinum-based chemotherapy by abrogating apoptosis, partly by reducing expression of Smad3.
Advisors/Committee Members: Pran K. Datta (committee member), Mark deCaestecker (committee member), Lawrence J. Marnett (committee member), David P. Carbone (committee member), Jin Chen (Committee Chair).
Subjects/Keywords: Smoking; Lung cancer; Smad3; Chemoresistance
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APA (6th Edition):
Samanta, D. (2012). Long-term smoking-mediated downregulation of Smad3 induces tumorigenicity and carboplatin resistance in non-small cell lung cancer. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12131
Chicago Manual of Style (16th Edition):
Samanta, Debangshu. “Long-term smoking-mediated downregulation of Smad3 induces tumorigenicity and carboplatin resistance in non-small cell lung cancer.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 27, 2021.
http://hdl.handle.net/1803/12131.
MLA Handbook (7th Edition):
Samanta, Debangshu. “Long-term smoking-mediated downregulation of Smad3 induces tumorigenicity and carboplatin resistance in non-small cell lung cancer.” 2012. Web. 27 Jan 2021.
Vancouver:
Samanta D. Long-term smoking-mediated downregulation of Smad3 induces tumorigenicity and carboplatin resistance in non-small cell lung cancer. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1803/12131.
Council of Science Editors:
Samanta D. Long-term smoking-mediated downregulation of Smad3 induces tumorigenicity and carboplatin resistance in non-small cell lung cancer. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/12131
Vanderbilt University
9.
Meador, Catherine Belle.
Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma.
Degree: PhD, Cancer Biology, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/13334
► EGFR-mutant lung cancers are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs; erlotinib/gefitinib/afatinib), but tumors develop drug resistance within 9-16 months. Resistance to gefitinib/erlotinib commonly…
(more)
▼ EGFR-mutant
lung cancers are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs; erlotinib/gefitinib/afatinib), but tumors develop drug resistance within 9-16 months. Resistance to gefitinib/erlotinib commonly occurs via a second-site EGFR mutation, T790M. Two strategies to overcome T790M+ resistance are mutant-specific EGFR TKIs, such as AZD9291, and dual inhibition of EGFR with afatinib plus the anti-EGFR antibody, cetuximab (A+C). Unfortunately, ‘second-line’ acquired resistance to A+C and AZD9291, after ‘first-line’ acquired resistance to erlotinib/gefitinib/afatinib, also occurs. To prevent/delay resistance to AZD9291, the combination of AZD9291 plus selumetinib (MEK1/2 inhibitor; AZD6244/ARRY-142886) is also currently being tested in a Phase I clinical trial (NCT02143466). The effects of sequential and combination treatment with various anti-EGFR agents on tumor evolution and drug resistance are largely unknown. In these studies, we modeled drug resistance pre-clinically to: 1. Assess the heterogeneity of mechanisms of first-line resistance to erlotinib and afatinib 2. Determine the optimum order of treatment with A+C vs. AZD9291 in the setting of T790M+ EGFR-mutant
lung tumors 3. Elucidate mechanisms of first- and second-line acquired resistance to AZD9291 and 4. Elucidate mechanisms of resistance to AZD9291 plus selumetinib. Next-generation sequencing of genomic DNA from cell line models of resistance to erlotinib/afatinib revealed multiple potentially functional genomic changes within a given pool of resistant cells (including T790M). We also found that AZD9291 is more potent than A+C at inhibiting cell growth in the setting of T790M+ resistance to erlotinib. A+C-resistant cell lines remain sensitive to AZD9291, but AZD9291-resistant cell lines are cross-resistant to A+C. Resistance to AZD9291 is associated with dysregulation of MAPK signaling and can be overcome by addition of the MEK 1/2 inhibitor, selumetinib. Finally, AZD9291 plus selumetinib-resistant cell lines display increased baseline phospho-MEK/ERK and are sensitive to in vitro treatment with an ERK inhibitor, SCH772984 or alternative MEK inhibitor, trametinib. These studies provide a more comprehensive understanding of how EGFR-mutant tumors undergo rewiring of their signaling circuitry in response to single-agent EGFR- and combined EGFR+MEK-inhibition. This work, emphasizing a mechanistic understanding of the effects of therapies on tumor evolution, provides a framework for future clinical trials testing different treatment sequences.
Advisors/Committee Members: Christine Lovly (committee member), Jennifer Pietenpol (committee member), William Pao (committee member), Rebecca Cook (Committee Chair).
Subjects/Keywords: targeted therapy; EGFR; lung cancer
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APA (6th Edition):
Meador, C. B. (2015). Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/13334
Chicago Manual of Style (16th Edition):
Meador, Catherine Belle. “Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed January 27, 2021.
http://hdl.handle.net/1803/13334.
MLA Handbook (7th Edition):
Meador, Catherine Belle. “Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma.” 2015. Web. 27 Jan 2021.
Vancouver:
Meador CB. Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1803/13334.
Council of Science Editors:
Meador CB. Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/13334
Penn State University
10.
Crampsie, Melissa Ashley.
INVESTIGATION OF THE MECHANISM OF ACTION OF ISOTHIOCYANATE
DERIVED ISOSELENOCYANATES AND THE CHEMOPREVENTIVE POTENTIAL OF
PHENYLBUTYL ISOSELENOCYANATE
.
Degree: 2011, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/12391
► Goals of Dissertation Research Lung cancer is currently the leading cause of cancer deaths among men and women and has a survival rate of only…
(more)
▼ Goals of Dissertation Research
Lung cancer is currently the leading cause of
cancer deaths among men and women and has a survival rate of only 16%. Because nearly 90% of
lung cancer cases are attributed to smoking tobacco and tobacco related
lung cancer has a latency period of 20-30 years from time of exposure to invasive disease, intervention before invasive disease with a chemical agent, termed chemoprevention, is a well suited approach for this particular disease. Research suggests that many natural compounds, often found in the human diet, have chemopreventive properties and are actively being explored and/or can make excellent lead compounds. Our lab, using rational drug design techniques, developed a novel isoselenocyanate compound known as phenylbutyl isoselenocyanate (ISC-4) based on naturally occurring compounds found in cruciferous vegetables. The central hypothesis of this research was that ISC-4, based on its design, would function as a potent and effective anti-
cancer agent and could be used as a chemopreventive agent.
Specific Aims
Specific Aim 1: To determine the effects of replacing the sulfur atom of a panel of phenyl alkyl isothiocyanates with selenium to form a new panel of phenyl alkyl isoselenocyanates (Chapter 2). A structure activity study was performed on the panel of parent isothiocyanate compounds and the resulting panel of isoselenocyanate compounds to determine if mechanistic characteristics were retained and to ascertain a reason for increased activity.
Specific Aim 2: Testing the hypothesis that ISC-4 has potential as a chemopreventive agent (Chapter 3). This drug was found to potently target and inhibit carcinogen bioactivation by cytochrome P450 enzymes, including the tobacco specific nitrosamine procarcinogen, N-nitrosyl ketone (NNK). When bioactivated, NNK can lead to mutations in DNA and ultimately result in tumorigenesis. A series of experiments were conducted to assess chemopreventive properties including bioavailability, anti-initiation, and DNA adduct studies, all of which were needed as proof of concept before performing an animal bioassay.
Specific Aim 3: Testing ISC-4 as a chemopreventive agent in a
lung cancer chemoprevention bioassay (Chapter 4). Using an A/J mouse model, ISC-4 at varying doses and along with its sulfur analog PBITC were tested for the ability to inhibit NNK induced
lung tumorigenesis over a 24 week period of time.
Original Breakthroughs and Findings
Isoselenocyanate (ISC) compounds were actually found to have increased activity with cellular thiols compared to their corresponding sulfur analogs leading to the hypothesis that specific protein modifications and redox activity in the cell are responsible for the increased activities seen with the ISC compounds. As Phase I cytochrome P450s were identified early as a significant protein target of ISC-4, the
cancer chemopreventive properties of this compound were explored. ISC-4 was found to be orally bioavailable, able to transcriptionally induce Phase II detoxification enzymes, and inhibit DNA adduct…
Advisors/Committee Members: Shantu G Amin, Dissertation Advisor/Co-Advisor, Shantu G Amin, Committee Chair/Co-Chair, Arun Kumar Sharma, Committee Chair/Co-Chair, Kelly J Karpa, Committee Member, Bogdan Prokopczyk, Committee Member, Gary H Perdew, Committee Member, Richard Robert Young, Committee Member.
Subjects/Keywords: ISC-4; lung cancer; chemoprevention
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MLA ·
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APA (6th Edition):
Crampsie, M. A. (2011). INVESTIGATION OF THE MECHANISM OF ACTION OF ISOTHIOCYANATE
DERIVED ISOSELENOCYANATES AND THE CHEMOPREVENTIVE POTENTIAL OF
PHENYLBUTYL ISOSELENOCYANATE
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12391
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):
Crampsie, Melissa Ashley. “INVESTIGATION OF THE MECHANISM OF ACTION OF ISOTHIOCYANATE
DERIVED ISOSELENOCYANATES AND THE CHEMOPREVENTIVE POTENTIAL OF
PHENYLBUTYL ISOSELENOCYANATE
.” 2011. Thesis, Penn State University. Accessed January 27, 2021.
https://submit-etda.libraries.psu.edu/catalog/12391.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Crampsie, Melissa Ashley. “INVESTIGATION OF THE MECHANISM OF ACTION OF ISOTHIOCYANATE
DERIVED ISOSELENOCYANATES AND THE CHEMOPREVENTIVE POTENTIAL OF
PHENYLBUTYL ISOSELENOCYANATE
.” 2011. Web. 27 Jan 2021.
Vancouver:
Crampsie MA. INVESTIGATION OF THE MECHANISM OF ACTION OF ISOTHIOCYANATE
DERIVED ISOSELENOCYANATES AND THE CHEMOPREVENTIVE POTENTIAL OF
PHENYLBUTYL ISOSELENOCYANATE
. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Jan 27].
Available from: https://submit-etda.libraries.psu.edu/catalog/12391.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Crampsie MA. INVESTIGATION OF THE MECHANISM OF ACTION OF ISOTHIOCYANATE
DERIVED ISOSELENOCYANATES AND THE CHEMOPREVENTIVE POTENTIAL OF
PHENYLBUTYL ISOSELENOCYANATE
. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12391
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Miami
11.
Milone, Mary Anne.
The Level of Hope in Patients Receiving Treatment for the Diagnosis of Lung Cancer.
Degree: PhD, Nursing (Nursing), 2010, University of Miami
URL: https://scholarlyrepository.miami.edu/oa_dissertations/409
► Lung cancer is the most common cause of cancer deaths worldwide. Hope is considered essential to life and has been positively associated with coping.…
(more)
▼ Lung cancer is the most common cause of
cancer deaths worldwide. Hope is considered essential to life and has been positively associated with coping. The purpose of this study was to describe the level of hope in patients receiving medical treatment for
lung cancer. The study was guided by Dufault and Martocchio's multidimensional theoretical model of hope. A total of 167 patients were recruited for this cross sectional descriptive study from oncology clinics in the Southeast United States. Each participant completed a nine-item demographic self-survey questionnaire and a twelve-item, four point Likert-type Herth Hope Index (possible scores 12-48, higher score = higher hope) to measure the level of hope. Clinical information included
lung cancer type, stage of
lung cancer, and time since diagnosis. The overall total mean hope score was 41.48 (SD = 5.10). This finding suggests that although
lung cancer patients may be at risk for lower hope scores, this study demonstrated that
lung cancer patients continue to hope throughout their disease trajectory. The other major findings demonstrated that widow/widowers (n = 14, 8%), were more hopeful (M = 42.57) than divorced (n = 36, 22%), (M = 39.29) and Blacks/African Americans (n = 22, 13.2%) had higher levels of hope (M = 43.22) than Whites/Caucasians (n = 140, 83%) (M = 41.26). Participants undergoing second line of chemotherapy treatment n = 30 (18%), were more hopeful 43.63(4.99) compared to all others. Future studies may include measuring hope at the time of diagnosis and throughout the disease trajectory, as well as at multiple data points during different lines of chemotherapy treatment.
Advisors/Committee Members: Denise M. Korniewicz, Stephen Sapp, Rosemary Hall, Lucy Chua.
Subjects/Keywords: Cancer; Lung; Palliative; Hope
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MLA ·
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Export
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Manager
APA (6th Edition):
Milone, M. A. (2010). The Level of Hope in Patients Receiving Treatment for the Diagnosis of Lung Cancer. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/409
Chicago Manual of Style (16th Edition):
Milone, Mary Anne. “The Level of Hope in Patients Receiving Treatment for the Diagnosis of Lung Cancer.” 2010. Doctoral Dissertation, University of Miami. Accessed January 27, 2021.
https://scholarlyrepository.miami.edu/oa_dissertations/409.
MLA Handbook (7th Edition):
Milone, Mary Anne. “The Level of Hope in Patients Receiving Treatment for the Diagnosis of Lung Cancer.” 2010. Web. 27 Jan 2021.
Vancouver:
Milone MA. The Level of Hope in Patients Receiving Treatment for the Diagnosis of Lung Cancer. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2021 Jan 27].
Available from: https://scholarlyrepository.miami.edu/oa_dissertations/409.
Council of Science Editors:
Milone MA. The Level of Hope in Patients Receiving Treatment for the Diagnosis of Lung Cancer. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/409
University of Debrecen
12.
Zeevi, Chen.
Chemotherapy and biological treatment of lung cancer
.
Degree: DE – Általános Orvostudományi Kar, University of Debrecen
URL: http://hdl.handle.net/2437/247211
Subjects/Keywords: lung cancer
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APA ·
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MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Zeevi, C. (n.d.). Chemotherapy and biological treatment of lung cancer
. (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/247211
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zeevi, Chen. “Chemotherapy and biological treatment of lung cancer
.” Thesis, University of Debrecen. Accessed January 27, 2021.
http://hdl.handle.net/2437/247211.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zeevi, Chen. “Chemotherapy and biological treatment of lung cancer
.” Web. 27 Jan 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
Zeevi C. Chemotherapy and biological treatment of lung cancer
. [Internet] [Thesis]. University of Debrecen; [cited 2021 Jan 27].
Available from: http://hdl.handle.net/2437/247211.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
Zeevi C. Chemotherapy and biological treatment of lung cancer
. [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/247211
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Boston University
13.
Perez-Rogers, Joseph.
Development of a minimally invasive molecular biomarker for early detection of lung cancer.
Degree: PhD, Bioinformatics GRS, 2017, Boston University
URL: http://hdl.handle.net/2144/21969
► The diagnostic evaluation of ever smokers with pulmonary nodules represents a growing clinical challenge due to the implementation of lung cancer screening. The high false-positive…
(more)
▼ The diagnostic evaluation of ever smokers with pulmonary nodules represents a growing clinical challenge due to the implementation of lung cancer screening. The high false-positive rate of screening frequently results in the use of unnecessary invasive procedures in patients who are ultimately diagnosed as benign, clearly highlighting the need for additional diagnostic approaches. We previously derived and validated a bronchial epithelial gene-expression biomarker to detect lung cancer in ever smokers. However, bronchoscopy is not always chosen as a diagnostic modality. Given that bronchial and nasal epithelial gene-expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene-expression might also be detectable in the more readily accessible nasal epithelium.
Nasal epithelial brushings were prospectively collected from ever smokers undergoing diagnostic evaluation for lung cancer in the AEGIS-1 (n=375) and AEGIS-2 (n=130) clinical trials and gene-expression profiled using microarrays. The computational framework used to discover biomarkers in these data was formalized and implemented in an open-source R-package.
We identified 535 genes in the nasal epithelium of AEGIS-1 patients whose expression was associated with lung cancer status. Using matched bronchial gene-expression data from a subset of these patients, we found significantly concordant cancer-associated gene-expression alterations between the two airway sites. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors and nasal gene-expression had significantly higher AUC (0.81) and sensitivity (0.91) than the clinical-factor model alone in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury extends to the nose and demonstrates the potential of using nasal gene-expression as a non-invasive biomarker for lung cancer detection.
The framework for deriving this biomarker was generalized and implemented in an open-source R-package. The package provides a computational pipeline to compare biomarker development strategies using microarray data. The results from this pipeline can be used to highlight the optimal model development parameters for a given dataset leading to more robust and accurate models. This package provides the community with a novel and powerful tool to facilitate biomarker discovery in microarray data.
Subjects/Keywords: Bioinformatics; Biomarker; Classifier; Lung cancer
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APA (6th Edition):
Perez-Rogers, J. (2017). Development of a minimally invasive molecular biomarker for early detection of lung cancer. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/21969
Chicago Manual of Style (16th Edition):
Perez-Rogers, Joseph. “Development of a minimally invasive molecular biomarker for early detection of lung cancer.” 2017. Doctoral Dissertation, Boston University. Accessed January 27, 2021.
http://hdl.handle.net/2144/21969.
MLA Handbook (7th Edition):
Perez-Rogers, Joseph. “Development of a minimally invasive molecular biomarker for early detection of lung cancer.” 2017. Web. 27 Jan 2021.
Vancouver:
Perez-Rogers J. Development of a minimally invasive molecular biomarker for early detection of lung cancer. [Internet] [Doctoral dissertation]. Boston University; 2017. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/2144/21969.
Council of Science Editors:
Perez-Rogers J. Development of a minimally invasive molecular biomarker for early detection of lung cancer. [Doctoral Dissertation]. Boston University; 2017. Available from: http://hdl.handle.net/2144/21969
Delft University of Technology
14.
Tolios, I. (author).
Visual Analysis of Lung Cancer Imaging Data Using Multidimensional Projections Techniques.
Degree: 2016, Delft University of Technology
URL: http://resolver.tudelft.nl/uuid:103551c5-8e23-4dd0-8b25-6e54f77b2dba
► Lung tumors are heterogeneous entities consisting of distinct intra-tumor regions with different biological characteristics. Currently, the only means to explore and analyze these distinct intra-tumor…
(more)
▼ Lung tumors are heterogeneous entities consisting of distinct intra-tumor regions with different biological characteristics. Currently, the only means to explore and analyze these distinct intra-tumor regions is to inspect several image acquisitions. From these, per-voxel functional tissue parameters, representative of tissue properties, are extracted. This results in a high-dimensional imaging-derived feature space. However, the exploration and analysis of tumor heterogeneity based on the derived imaging data is a complex and time demanding task, due to its multi-modality and high dimensionality. Visual Analytics techniques can help optimize this process. Views based on dimensionality reduction are a common strategy to offer insight in high-dimensional feature spaces by constructing low-dimensional representations of the initial high-dimensional data. There is a great range of dimensionality reduction techniques. For this reason, we have to find the most suitable for visualizing and analyzing lung cancer imaging data. To this end, we selected and evaluated those who according to our opinion meet our visualization requirement. This requirement is the preservation of the local structure of the data in the low-dimensional representation, as an indication of intra-tumor regions being grouped together in the high-dimensional space. For the selection of the examined techniques, we evaluate them both qualitatively and quantitatively. The qualitative evaluation is performed by visually inspecting the low-dimensional mappings, while the quantitative by applying specific metrics. The best performing techniques are introduced in an existing visualization framework [1] and their anatomical coherence is examined. However, additional functionalities are introduced, hereby enhancing its exploratory value. Side-by-side comparison of multiple low-dimensional projections and automatic clustering on the embeddings are added in the tool. The proposed tool is evaluated by our collaborating clinical researcher with three real patient cases. Overall, the tool provided promising results, making easier the identification, inspection and hypothesis generation for intra-tumor regions.
Electrical Engineering, Mathematics and Computer Science
Intelligent Systems
Computer Graphics Group
Advisors/Committee Members: Vilanova Bartroli, A. (mentor).
Subjects/Keywords: lung; cancer; medical; visualization
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APA ·
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MLA ·
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Manager
APA (6th Edition):
Tolios, I. (. (2016). Visual Analysis of Lung Cancer Imaging Data Using Multidimensional Projections Techniques. (Masters Thesis). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:103551c5-8e23-4dd0-8b25-6e54f77b2dba
Chicago Manual of Style (16th Edition):
Tolios, I (author). “Visual Analysis of Lung Cancer Imaging Data Using Multidimensional Projections Techniques.” 2016. Masters Thesis, Delft University of Technology. Accessed January 27, 2021.
http://resolver.tudelft.nl/uuid:103551c5-8e23-4dd0-8b25-6e54f77b2dba.
MLA Handbook (7th Edition):
Tolios, I (author). “Visual Analysis of Lung Cancer Imaging Data Using Multidimensional Projections Techniques.” 2016. Web. 27 Jan 2021.
Vancouver:
Tolios I(. Visual Analysis of Lung Cancer Imaging Data Using Multidimensional Projections Techniques. [Internet] [Masters thesis]. Delft University of Technology; 2016. [cited 2021 Jan 27].
Available from: http://resolver.tudelft.nl/uuid:103551c5-8e23-4dd0-8b25-6e54f77b2dba.
Council of Science Editors:
Tolios I(. Visual Analysis of Lung Cancer Imaging Data Using Multidimensional Projections Techniques. [Masters Thesis]. Delft University of Technology; 2016. Available from: http://resolver.tudelft.nl/uuid:103551c5-8e23-4dd0-8b25-6e54f77b2dba
Boston University
15.
Garrison, Carly.
Characterizing microRNA regulators of lung disease.
Degree: PhD, Genetics & Genomics, 2016, Boston University
URL: http://hdl.handle.net/2144/14598
► Lung diseases are one of the leading causes of mortality and morbidity worldwide. Understanding these diseases at a molecular level remains a critical component to…
(more)
▼ Lung diseases are one of the leading causes of mortality and morbidity worldwide. Understanding these diseases at a molecular level remains a critical component to developing effective therapeutics. Previous work has shown that gene expression alterations play an important role in disease initiation, maintenance, and progression as well as serve as diagnostic tools in disease. However, much remains to be uncovered regarding the role that microRNAs play in both healthy and diseased lung tissue. This thesis seeks to utilize methods of bioinformatics, cell biology, and molecular biology to examine the effect of miR-4423 on lung epithelial cell differentiation (Aim 1), miR-424 on never smoker derived lung adenocarcinoma (Aim 2), and miR-34c isomiRs in interstitial lung disease (ILD) (Aim 3).
First, we examined the role of miR-4423 in lung mucociliary epithelium by employing the use of an air-liquid interface culture system, finding miR-4423 has an effect in ciliated cell differentiation and that a loss of miR-4423 is associated with cancer progression. These findings suggest that miR-4423’s actions in airway epithelium differentiation may potentially provide a therapeutic role in lung cancer. Next, we validated transcriptomic differences between lung tumor tissues resected from never and ever smokers. Specifically, miR-424, a predicted regulator of a large number of gene expression changes in never smoker lung adenocarcinoma, was found to regulate cell migration, potentially identifying a novel target and/or pathway for therapeutic action. Lastly, the function of microRNA isomiRs is relatively unknown. We validated miR-34c as upregulated in ILD and modulated both miR-34c and a miR-34c 5’ isomiR in lung relevant cell lines to explore their differing biological roles. We found that they are capable of targeting differing mRNA, indicating an independent role for isomiRs in disease.
The studies contained in this dissertation offer valuable insight into the biology of microRNAs in the lung and how they might be employed as therapeutic targets for a number of common lung diseases. In addition, biological insights into the complexity of microRNAs in the lung highlight the need to better understand diseases influenced by microRNA expression and microRNA variants in regards to actionable therapeutics.
Subjects/Keywords: Genetics; Cancer; Lung; MicroRNA; Therapeutic
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APA (6th Edition):
Garrison, C. (2016). Characterizing microRNA regulators of lung disease. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/14598
Chicago Manual of Style (16th Edition):
Garrison, Carly. “Characterizing microRNA regulators of lung disease.” 2016. Doctoral Dissertation, Boston University. Accessed January 27, 2021.
http://hdl.handle.net/2144/14598.
MLA Handbook (7th Edition):
Garrison, Carly. “Characterizing microRNA regulators of lung disease.” 2016. Web. 27 Jan 2021.
Vancouver:
Garrison C. Characterizing microRNA regulators of lung disease. [Internet] [Doctoral dissertation]. Boston University; 2016. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/2144/14598.
Council of Science Editors:
Garrison C. Characterizing microRNA regulators of lung disease. [Doctoral Dissertation]. Boston University; 2016. Available from: http://hdl.handle.net/2144/14598
University of Melbourne
16.
GRANGER, CATHERINE.
Engagement in physical activity following a diagnosis of non-small cell lung cancer.
Degree: 2013, University of Melbourne
URL: http://hdl.handle.net/11343/38181
► Lung cancer is the most prevalent type of cancer worldwide and associated with the highest mortality. Individuals with non-small cell lung cancer (NSCLC) experience symptoms…
(more)
▼ Lung cancer is the most prevalent type of cancer worldwide and associated with the highest mortality. Individuals with non-small cell lung cancer (NSCLC) experience symptoms which frequently lead to a vicious cycle of inactivity and functional decline. Whilst there is a strong body of research published regarding the physical activity levels of many cancer types and the role of exercise in the management of cancer, limited work has been performed in NSCLC.
This first study of the thesis was a systematic review which synthesized the measurement properties of outcomes used to assess physical activity, functional capacity and muscle strength of individuals with NSCLC. Thirteen outcome measures were identified. Functional capacity was assessed using the six- and twelve-minute walk tests; incremental- and endurance-shuttle walk tests; and the stair-climbing test. Physical activity was assessed using accelerometers and pedometers. Muscle strength was assessed using five different tests. Thirty-one studies were identified which investigated the measurement properties of these outcome measures in NSCLC, most reporting on the criterion or construct validity of the tests. Little work has been done regarding reliability or responsiveness. Further studies are needed to establish measurement properties of standardised field tests for individuals with NSCLC to allow the most appropriate choice for clinical practice and when designing research trials.
Study 2 was a multi-site prospective observational study where the physical activity levels of individuals with NSCLC were measured across the trajectory of disease. Fifty participants with newly diagnosed stage I-IIIB NSCLC and 35 similar-aged healthy individuals were included. At diagnosis individuals with NSCLC were engaged in lower levels of physical activity than similar-aged healthy individuals and had worse functional capacity, strength, nutritional status, HRQoL, and higher levels of depression. Over six months individuals with NSCLC experienced a decline in self-reported physical activity, functional capacity and strength. Higher levels of physical activity were associated with better functional capacity, strength, nutritional status and HRQoL; and lower levels of depression, anxiety and symptoms.
In study 3 a systematic review was performed to synthesize the role of exercise in NSCLC. Sixteen studies were included in the review. No studies were conducted in Australia. Results demonstrated that exercise intervention for individuals with NSCLC is safe before and after treatment. Interventions pre-operatively or post-treatment are associated with positive benefits on functional capacity, symptoms and some domains of HRQoL. The majority of studies were small case series therefore results should be viewed with caution until larger randomised controlled trials (RCTs) are completed.
A pilot randomised…
Subjects/Keywords: lung cancer; physical activity; exercise
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APA (6th Edition):
GRANGER, C. (2013). Engagement in physical activity following a diagnosis of non-small cell lung cancer. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38181
Chicago Manual of Style (16th Edition):
GRANGER, CATHERINE. “Engagement in physical activity following a diagnosis of non-small cell lung cancer.” 2013. Doctoral Dissertation, University of Melbourne. Accessed January 27, 2021.
http://hdl.handle.net/11343/38181.
MLA Handbook (7th Edition):
GRANGER, CATHERINE. “Engagement in physical activity following a diagnosis of non-small cell lung cancer.” 2013. Web. 27 Jan 2021.
Vancouver:
GRANGER C. Engagement in physical activity following a diagnosis of non-small cell lung cancer. [Internet] [Doctoral dissertation]. University of Melbourne; 2013. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/11343/38181.
Council of Science Editors:
GRANGER C. Engagement in physical activity following a diagnosis of non-small cell lung cancer. [Doctoral Dissertation]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/38181
Queens University
17.
Ahn, Joseph.
Fer Protein-Tyrosine Kinase as a Potential Therapeutic Target in Lung Cancer
.
Degree: Biochemistry, 2012, Queens University
URL: http://hdl.handle.net/1974/7441
► Fer is a ubiquitously expressed non-receptor protein-tyrosine kinase that regulates normal physiology through signaling in a variety of cell types. Fer signals downstream of growth…
(more)
▼ Fer is a ubiquitously expressed non-receptor protein-tyrosine kinase that regulates normal physiology through signaling in a variety of cell types. Fer signals downstream of growth factor receptors frequently activated or amplified in human cancers and Fer has been identified as a positive regulator of cancer progression in the prostate and liver. Epidermal growth factor (EGF) receptor (EGFR) is frequently activated due to gene amplification or gain-of-function mutations in non-small cell lung carcinomas (NSCLC) leading to aggressive tumours that frequently metastasize. Since EGFR activates Fer, I tested whether Fer participates in EGFR-driven NSCLC cell migration, tumour progression and metastasis. Here, I show that Fer is expressed in cell lines derived from both normal lung epithelia and NSCLC and is activated following EGF treatment of NSCLC cells. To probe Fer function we used a lentiviral shRNA system to achieve stable knock-down (KD) of Fer in H1299 cells. Compared to control cells, Fer KD cells displayed a significant reduction in EGF-induced cell migration and invasion which correlated with reduced phosphorylation of the guanine nucleotide exchange factor Vav2. Consistent with Vav2 phosphorylation promoting Rac activation, we observed reduced localization of active, GTP- bound Rac1 to the leading edge of Fer KD cells treated with EGF. Tumour xenograft experiments were performed to test the role of Fer in NSCLC tumour progression and metastasis in immune compromised mice. Growth of primary tumours was normal, despite efficient Fer silencing in vivo. Interestingly, fewer spontaneous lung metastases were observed from subcutaneous Fer KD tumours compared to control. However, no differences were observed in lung seeding efficiency in experimental metastasis assays, suggesting that Fer may play a role in early stages of metastasis. Together, this study identifies Fer as a potential new therapeutic target for the treatment of EGFR-driven lung cancer metastasis.
Subjects/Keywords: FER Kinase
;
Lung Cancer
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APA (6th Edition):
Ahn, J. (2012). Fer Protein-Tyrosine Kinase as a Potential Therapeutic Target in Lung Cancer
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/7441
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):
Ahn, Joseph. “Fer Protein-Tyrosine Kinase as a Potential Therapeutic Target in Lung Cancer
.” 2012. Thesis, Queens University. Accessed January 27, 2021.
http://hdl.handle.net/1974/7441.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ahn, Joseph. “Fer Protein-Tyrosine Kinase as a Potential Therapeutic Target in Lung Cancer
.” 2012. Web. 27 Jan 2021.
Vancouver:
Ahn J. Fer Protein-Tyrosine Kinase as a Potential Therapeutic Target in Lung Cancer
. [Internet] [Thesis]. Queens University; 2012. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1974/7441.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ahn J. Fer Protein-Tyrosine Kinase as a Potential Therapeutic Target in Lung Cancer
. [Thesis]. Queens University; 2012. Available from: http://hdl.handle.net/1974/7441
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Vanderbilt University
18.
Kaufman, Jacob Marcus.
LKB1 loss induces characteristic pathway activation in human tumors and confers sensitivity to MEK inhibition associated with attenuated PI3K-AKT-FOXO3 signaling.
Degree: PhD, Cancer Biology, 2013, Vanderbilt University
URL: http://hdl.handle.net/1803/14385
► Inactivation of STK11/LKB1 is one of the most common genetic events in lung cancer, and understanding the cellular phenotypes and molecular pathways altered as a…
(more)
▼ Inactivation of STK11/LKB1 is one of the most common genetic events in
lung cancer, and understanding the cellular phenotypes and molecular pathways altered as a consequence will aid the development of therapeutic strategies targeting LKB1-deficient cancers. We report the comprehensive analysis of gene and protein expression patterns associated with LKB1 loss in
lung adenocarcinomas, through which we identify hallmarks of altered tumor metabolism and downregulation of the PI3K/AKT pathway. Significant differences are observed between human tumors and those derived from a genetically engineered mouse model of LKB1 loss. A 16-gene signature is predictive of both mutational and non-mutational LKB1 loss in human tumors. Cell lines expressing this signature show increased sensitivity to MEK inhibition, independent of mutations in RAS and RAF family members. Restoration of LKB1 in
lung cancer cell lines downregulates the gene expression pattern, attenuates FOXO3, and induces resistance to MEK inhibition. These findings identify characteristic phenotypic features of LKB1-deficient tumors and identify LKB1 loss as a novel determinant of MEK sensitivity.
Advisors/Committee Members: David Carbone (committee member), Ethan Lee (committee member), Pierre Massion (committee member), Alissa Weaver (committee member), William Pao (Committee Chair).
Subjects/Keywords: MEK inhibition; LKB1; lung cancer
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kaufman, J. M. (2013). LKB1 loss induces characteristic pathway activation in human tumors and confers sensitivity to MEK inhibition associated with attenuated PI3K-AKT-FOXO3 signaling. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14385
Chicago Manual of Style (16th Edition):
Kaufman, Jacob Marcus. “LKB1 loss induces characteristic pathway activation in human tumors and confers sensitivity to MEK inhibition associated with attenuated PI3K-AKT-FOXO3 signaling.” 2013. Doctoral Dissertation, Vanderbilt University. Accessed January 27, 2021.
http://hdl.handle.net/1803/14385.
MLA Handbook (7th Edition):
Kaufman, Jacob Marcus. “LKB1 loss induces characteristic pathway activation in human tumors and confers sensitivity to MEK inhibition associated with attenuated PI3K-AKT-FOXO3 signaling.” 2013. Web. 27 Jan 2021.
Vancouver:
Kaufman JM. LKB1 loss induces characteristic pathway activation in human tumors and confers sensitivity to MEK inhibition associated with attenuated PI3K-AKT-FOXO3 signaling. [Internet] [Doctoral dissertation]. Vanderbilt University; 2013. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1803/14385.
Council of Science Editors:
Kaufman JM. LKB1 loss induces characteristic pathway activation in human tumors and confers sensitivity to MEK inhibition associated with attenuated PI3K-AKT-FOXO3 signaling. [Doctoral Dissertation]. Vanderbilt University; 2013. Available from: http://hdl.handle.net/1803/14385
University of New South Wales
19.
Kumar, Shivani.
Towards MRI guided radiotherapy for lung cancer.
Degree: Clinical School - South Western Sydney, 2020, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/65529
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64674/SOURCE02?view=true
► Magnetic resonance imaging (MRI) is increasingly being incorporated in radiotherapy (RT) planning due to superior soft tissue contrast compared to CT, however its use for…
(more)
▼ Magnetic resonance imaging (MRI) is increasingly being incorporated in radiotherapy (RT) planning due to superior soft tissue contrast compared to CT, however its use for
lung cancer RT has been limited. This thesis addresses the feasibility and potential benefit of MRI for
lung cancer RT. A literature review on the feasibility of MRI in
lung RT identified that a combination of T2 and T1 weighted images can demonstrate tumour infiltration and mediastinal nodal involvement. Using this information, a free-breathing protocol was developed to aid target volume delineation and overcome challenges with breath-hold non-compliance. An assessment of a radiologist-led workshop on inter-observer variability in volume delineation showed no significant improvement.To assess the potential benefit of MRI for
lung RT, a prospective clinical trial was conducted. Inter-observer variability on target volume delineation for T2 MRI and CT was assessed. Volumes delineated on CT and T2 datasets showed significant differences in overlap measures (p<0.01). However inter-observer variability within each imaging modality demonstrated good agreement between observers (dice similarity coefficient ≥0.7), indicating that replacement of CT with T2 MRI did not have a negative impact on interobserver variability. Assessment of motion between 4DCT and cine MRI was investigated. Tumour motion between 4DCT and 2D cine MRI was shown to be similar, however cine MRI showed larger variation in superior inferior motion for individual patients. Cine MRI can potentially be used as a complementary imaging tool to 4DCT for motion definition. Potential application of MRI for adaptive RT (ART) was investigated by evaluating tumour changes on sequential imaging. Volumes delineated on cone beam CT and MRI were significantly different. Rate of primary tumour regression was shown to be similar, but nodal regression was greater on MRI. While further work is necessary to demonstrate the benefit of MRI to CBCT and CT, the results of this study provide initial data for incorporation of MRI for ART. This thesis suggests that MRI has the potential to enhance
lung cancer RT. However the differences demonstrated between MRI and current imaging modalities needs further investigation prior to any clinical implementation.
Advisors/Committee Members: Vinod, Shalini, Clinical School - South Western Sydney, Faculty of Medicine, UNSW, Holloway, Lois, Clinical School - South Western Sydney, Faculty of Medicine, UNSW.
Subjects/Keywords: Radiotherapy; MRI; Lung Cancer
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APA (6th Edition):
Kumar, S. (2020). Towards MRI guided radiotherapy for lung cancer. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/65529 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64674/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Kumar, Shivani. “Towards MRI guided radiotherapy for lung cancer.” 2020. Doctoral Dissertation, University of New South Wales. Accessed January 27, 2021.
http://handle.unsw.edu.au/1959.4/65529 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64674/SOURCE02?view=true.
MLA Handbook (7th Edition):
Kumar, Shivani. “Towards MRI guided radiotherapy for lung cancer.” 2020. Web. 27 Jan 2021.
Vancouver:
Kumar S. Towards MRI guided radiotherapy for lung cancer. [Internet] [Doctoral dissertation]. University of New South Wales; 2020. [cited 2021 Jan 27].
Available from: http://handle.unsw.edu.au/1959.4/65529 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64674/SOURCE02?view=true.
Council of Science Editors:
Kumar S. Towards MRI guided radiotherapy for lung cancer. [Doctoral Dissertation]. University of New South Wales; 2020. Available from: http://handle.unsw.edu.au/1959.4/65529 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:64674/SOURCE02?view=true
University of New South Wales
20.
Luk, Peter Ping-Kit.
The influence of the EGFR pathway in modulating the efficacy of gemcitabine.
Degree: Clinical School - St George Hospital, 2011, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/50384
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:9271/SOURCE02?view=true
► Multiple anti-cancer drugs are often combined to increase their effectiveness. This study investigates the combination between an epidermal growth factor receptor (EGFR) inhibitor and gemcitabine,…
(more)
▼ Multiple anti-
cancer drugs are often combined to increase their effectiveness. This study investigates the combination between an epidermal growth factor receptor (EGFR) inhibitor and gemcitabine, a commonly used chemotherapy agent that causes cell death by incorporation into DNA. Clinical trials combining EGFR inhibitors with gemcitabine-based chemotherapy in non-small cell
lung cancer (NSCLC) have not produced a survival advantage. This may be caused by antagonism between the two drugs or mutations that promote such, possibly RAS mutation. Furthermore, ERK, a critical growth regulator downstream of RAS, may play a role. Therefore the aim of this study is to explore the cytotoxic interaction between gemcitabine and an EGFR inhibitor as well as the mechanisms underlying this interaction. The impact of KRAS mutation will also be investigated. Two NSCLC cell lines (A549 and H322) with divergent KRAS mutation status were treated with gemcitabine and the EGFR inhibitor AG1478. Cytotoxic interaction was determined with median effect analysis. Cell cycle alteration was assessed using flow cytometry while EGFR downstream signalling was assessed using immunoblotting and ELISA. ERK was inhibited using U0126 to explore the effect on cytotoxic interaction. The effect of KRAS was explored using siRNA-mediated knockdown in A549. Cytotoxic interaction was concentration and schedule dependent with antagonism in AG1478 pre-treatment and high concentration AG1478. G1 arrest, being observed with both high concentration AG1478 and high concentration gemcitabine, was inconsistently associated with antagonism. On the other hand, ERK phosphorylation was increased by gemcitabine and its suppression by AG1478 was related to antagonism particularly in H322. Antagonism caused by inhibition of ERK was further confirmed following U0126 treatment. Greater antagonism was observed in the KRAS mutant cell line and KRAS knockdown by siRNA resulted in increased sensitivity to AG1478 as well as combination treatment. In conclusion, ERK appears to be an important determinant of cytotoxic interaction with its phosphorylation favouring synergism. However, the impact of other EGFR downstream pathways warrants further investigation. Furthermore, KRAS mutation confers resistance to AG1478 and combination treatment. Both ERK and KRAS may potentially be important biomarkers for EGFR inhibitor combination therapy.
Advisors/Committee Members: Links, Matthew, Clinical School - St George Hospital, Faculty of Medicine, UNSW.
Subjects/Keywords: Lung cancer; Gemcitabine; EGFR
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APA (6th Edition):
Luk, P. P. (2011). The influence of the EGFR pathway in modulating the efficacy of gemcitabine. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/50384 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:9271/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Luk, Peter Ping-Kit. “The influence of the EGFR pathway in modulating the efficacy of gemcitabine.” 2011. Doctoral Dissertation, University of New South Wales. Accessed January 27, 2021.
http://handle.unsw.edu.au/1959.4/50384 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:9271/SOURCE02?view=true.
MLA Handbook (7th Edition):
Luk, Peter Ping-Kit. “The influence of the EGFR pathway in modulating the efficacy of gemcitabine.” 2011. Web. 27 Jan 2021.
Vancouver:
Luk PP. The influence of the EGFR pathway in modulating the efficacy of gemcitabine. [Internet] [Doctoral dissertation]. University of New South Wales; 2011. [cited 2021 Jan 27].
Available from: http://handle.unsw.edu.au/1959.4/50384 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:9271/SOURCE02?view=true.
Council of Science Editors:
Luk PP. The influence of the EGFR pathway in modulating the efficacy of gemcitabine. [Doctoral Dissertation]. University of New South Wales; 2011. Available from: http://handle.unsw.edu.au/1959.4/50384 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:9271/SOURCE02?view=true
21.
Michel, Noémie.
Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire : Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiology.
Degree: Docteur es, Sciences de la Vie et de la Santé, 2013, Université François-Rabelais de Tours
URL: http://www.theses.fr/2013TOUR3303
► Les kallicréines tissulaires humaines (KLK) ont récemment émergé comme une famille de protéases à serine pouvant jouer un rôle important dans la tumorigenèse. Le but…
(more)
▼ Les kallicréines tissulaires humaines (KLK) ont récemment émergé comme une famille de protéases à serine pouvant jouer un rôle important dans la tumorigenèse. Le but de cette étude a été de mieux comprendre comment KLK6 et KLK12 pourraient intervenir dans la physiopathologie pulmonaire. Nous avons démontré qu’une expression ectopique de KLK6 induisait la prolifération des cellules A549 d’une manière dépendante de son activité enzymatique, une résistance à l’apoptose, ainsi qu’une translocation nucléaire de la β-caténine. Nous avons également montré une voie de signalisation impliquée dans la prolifération induite par KLK6 impliquant PAR2, EGFR et ERK. Nous avons identifié de nouveaux subtrats pour KLK12 : les CCN. Nous avons démontré que le clivage de CCN1 et CCN5 par KLK12 limitait leurs fixations avec le VEGF, BMP2 et le TGF-β1.
Recently, human tissue kallikreins (KLK) emerged as a new family of serine proteases which might play a major role in the tumorigenesis. The project aims at determining the contribution of KLK6 and 12 in lung pathophysiology. We showed that ectopic KLK6 promoted A549 cell proliferation in a protease activity-dependant manner, inhibited cell apoptosis and induced β-catenin nuclear translocation. Furthermore, this study uncovered a signaling pathway mediated by KLK6 in promoting A549 cell proliferation trough activation of the PAR2-EGFR-ERK pathway.We have also identified novel substrates of KLK12, the CCN family. We reported that KLK12-mediated proteolysis of CCN1 and CCN5 can reduce or abolish the binding of VEGF, BMP2, and TGF-β1.
Advisors/Committee Members: Courty, Yves (thesis director), Heuzé-Vourc'h, Nathalie (thesis director).
Subjects/Keywords: Kallicréines; Cancer du poumon; Kallikreins; Lung cancer
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APA (6th Edition):
Michel, N. (2013). Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire : Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiology. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2013TOUR3303
Chicago Manual of Style (16th Edition):
Michel, Noémie. “Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire : Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiology.” 2013. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 27, 2021.
http://www.theses.fr/2013TOUR3303.
MLA Handbook (7th Edition):
Michel, Noémie. “Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire : Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiology.” 2013. Web. 27 Jan 2021.
Vancouver:
Michel N. Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire : Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiology. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2013. [cited 2021 Jan 27].
Available from: http://www.theses.fr/2013TOUR3303.
Council of Science Editors:
Michel N. Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire : Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiology. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2013. Available from: http://www.theses.fr/2013TOUR3303
Kansas State University
22.
Uppalapati, Lakshmi.
Peptides as
therapeutics and active gene delivery vehicles for cancer
treatment.
Degree: PhD, Department of
Agronomy, 2015, Kansas State University
URL: http://hdl.handle.net/2097/35231
► Over the years proteins/peptides have evolved as promising therapeutic agents in the treatment of cancer. Considering the advantages of peptides such as their small size,…
(more)
▼ Over the years proteins/peptides have evolved as
promising therapeutic agents in the treatment of
cancer.
Considering the advantages of peptides such as their small size,
ease of synthesis, tumor-penetrating ability and bio-compatibility,
present report discusses proof of concept for 1. C1B5 peptide of
protein kinase Cγ and a low dose of gemcitabine combination
treatment for peritoneally disseminated pancreatic
cancer and 2.
dTAT peptide nanoparticles mediated gene (angiotensin II type 2
receptor gene) therapy for
lung cancer. 1. A significant reduction
in intraperitoneally (IP) transplanted pancreatic carcinoma growth
was demonstrated with C1B5 peptide and gemcitabine co-treatment in
an immunocompetent mouse model. Increased number of Granzyme B
positive cells was observed in treated mice ascites, suggesting the
involvement of immune response in tumor attenuation. The strong
effect observed in combination treatment might be because of
increase in lymphocyte recruitment by gemcitabine followed by C1B5
peptide mediated CD8+ T-cells or NK cells activation apart from
direct
cancer cell apoptosis. 2. To test dTAT peptide nanoparticles
(dTAT NPs) mediated therapeutic gene delivery, luciferase reporter
gene containing dTAT nanoparticles were synthesized
(dTAT/pLUC/Ca2+). Synthesis conditions for nanoparticles were
optimized based on dTAT/pLUC/Ca2+ nanoparticles transfection
efficiency. With the optimized conditions, dTAT NPs containing
AT2R, TRAIL or miR-34a pDNA (dTAT/pAT2R, dTAT/TRAIL or dTAT/miR-
34a) were synthesized. Therapeutic potential of these NPs was
analyzed in
lung adenocarcinoma containing mice by administering
them intravenously (IV) or/and intratracheally (IV). Combination
treatment with the IV injection of the new dTAT/pAT2R/Ca2+
formulation and the IT injection of the original dTAT/pAT2R/Ca2+
formulation is effective in attenuation of developed human
bronchioloalveolar carcinoma in the SCID mouse lungs. Findings from
the above mentioned studies have vital clinical relevance as it
implies that peptides alone or when used as gene delivery systems
may prove to be beneficial in the treatment of various stages of
cancer.
Advisors/Committee Members: Masaaki Tamura.
Subjects/Keywords: Cancer
therapeutics;
Nanoparticle;
Intratracheal; Lung
cancer
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APA ·
Chicago ·
MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Uppalapati, L. (2015). Peptides as
therapeutics and active gene delivery vehicles for cancer
treatment. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/35231
Chicago Manual of Style (16th Edition):
Uppalapati, Lakshmi. “Peptides as
therapeutics and active gene delivery vehicles for cancer
treatment.” 2015. Doctoral Dissertation, Kansas State University. Accessed January 27, 2021.
http://hdl.handle.net/2097/35231.
MLA Handbook (7th Edition):
Uppalapati, Lakshmi. “Peptides as
therapeutics and active gene delivery vehicles for cancer
treatment.” 2015. Web. 27 Jan 2021.
Vancouver:
Uppalapati L. Peptides as
therapeutics and active gene delivery vehicles for cancer
treatment. [Internet] [Doctoral dissertation]. Kansas State University; 2015. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/2097/35231.
Council of Science Editors:
Uppalapati L. Peptides as
therapeutics and active gene delivery vehicles for cancer
treatment. [Doctoral Dissertation]. Kansas State University; 2015. Available from: http://hdl.handle.net/2097/35231
University of Louisville
23.
Muench, Edward David, 1987-.
The VEGF quadruplex-forming sequence inhibits lung cancer cell growth.
Degree: M. Eng., 2012, University of Louisville
URL: 10.18297/etd/1022
;
https://ir.library.louisville.edu/etd/1022
► Vascular endothelial growth factor (VEGF), a commonly overexpressed oncogene in a variety of malignancies including non-small cell lung cancer (NSCLC), is a key regulator of…
(more)
▼ Vascular endothelial growth factor (VEGF), a commonly overexpressed oncogene in a variety of malignancies including non-small cell
lung cancer (NSCLC), is a key regulator of angiogenesis promoting tumor survival, growth, and metastasis. The promoters of several
cancer-related genes, including VEGF, contain disproportionate sequences within nuclease hypersensitivity regions capable of forming quadruplex (fourstranded) DNA. The specific quadruplex forming sequence of interest is the 20 base pair polyG/polyC tract that codes for the VEGF promoter (VEGFq), which is located in the proximal promoter region upstream of the transcription initiation site. This oligonucleotide has been shown to have significant growth hindering effects when introduced in the NSCLC cell line, A549. To determine the biological role of VEGFq on non-small cell
lung cancer in vitro, cells were treated with either VEGFq or the corresponding mutant sequence (MutVEGF), which lacks the runs of guanines necessary for quadruplex formation. Circular dichroism spectroscopy confirmed that VEGFq formed a parallel quadruplex, while the MutVEGF sequence did not form a quadruplex structure. It is hypothesized that the considerable growth inhibition is caused by hindering the VEGF signaling pathway. The VEGF signaling cascade, which is normally triggered by VEGF binding to FLK1 (VEGF Receptor 2), is unable to function adequately due to decreased VEGF protein levels. This causes a disruption in the phosphorylation of target proteins including ERK1/2 and AKT/PKB, which in turn decreases overall cell proliferation. This observed decline in overall cell proliferation corresponded to decreased levels of VEGF protein expression, indicating that there is a direct correlation between the treatment and the changes in proliferation. A single treatment of A549 NSCLC cells with VEGFq caused a significant dose and time-dependent decrease in cell viability after 3 and 6 days as determined by MTT assay. Parallel treatment of nontransformed human fibroblast cells with VEGFq showed no changes in growth, demonstrating the
cancer specificity of VEGFq. Cell cycle analysis showed no changes in cell phases at 24, 48, 72 and 96 hours, indicating that VEGFq's effects due to a mechanism other than cell cycle arrest. Confocal microscopy and flow cytometry after 72 hours showed significant uptake and nuclear localization of VEGFq, but not MutVEGF. Boyden chamber invasion/migration measurement shows that the VEGFq treated cells have decreased cell movement, indicative of possible antiangiogenic effects as well. To determine the biological role of VEGFq on non-small cell
lung cancer in vivo, A549 cells were injected into nude mice and grown for 10 days prior to daily IP injections of 10 mg/kg VEGFq or the control vehicle for 14 days. Tumor progression was physically measured using calipers three times a week. Fluorescent imaging was used to detect the presence, stability, and distribution of Alexa Fluor 750-labeled VEGFq after injection into the mouse to ensure localization in the targeted…
Advisors/Committee Members: Miller, Donald M..
Subjects/Keywords: VEGF; Lung cancer; Quadruplex; Cancer; Oligonucleotide
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APA (6th Edition):
Muench, Edward David, 1. (2012). The VEGF quadruplex-forming sequence inhibits lung cancer cell growth. (Masters Thesis). University of Louisville. Retrieved from 10.18297/etd/1022 ; https://ir.library.louisville.edu/etd/1022
Chicago Manual of Style (16th Edition):
Muench, Edward David, 1987-. “The VEGF quadruplex-forming sequence inhibits lung cancer cell growth.” 2012. Masters Thesis, University of Louisville. Accessed January 27, 2021.
10.18297/etd/1022 ; https://ir.library.louisville.edu/etd/1022.
MLA Handbook (7th Edition):
Muench, Edward David, 1987-. “The VEGF quadruplex-forming sequence inhibits lung cancer cell growth.” 2012. Web. 27 Jan 2021.
Vancouver:
Muench, Edward David 1. The VEGF quadruplex-forming sequence inhibits lung cancer cell growth. [Internet] [Masters thesis]. University of Louisville; 2012. [cited 2021 Jan 27].
Available from: 10.18297/etd/1022 ; https://ir.library.louisville.edu/etd/1022.
Council of Science Editors:
Muench, Edward David 1. The VEGF quadruplex-forming sequence inhibits lung cancer cell growth. [Masters Thesis]. University of Louisville; 2012. Available from: 10.18297/etd/1022 ; https://ir.library.louisville.edu/etd/1022
Universiteit Utrecht
24.
Waal, L.M. de.
Treatment of subtypes in non-small cell lung cancer.
Degree: 2012, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/241663
► Lung cancer accounts for the highest number of cancer related deaths among all cancer patients. It has been well established that exposure to tobacco significantly…
(more)
▼ Lung cancer accounts for the highest number of
cancer related deaths among all
cancer patients. It has been well established that exposure to tobacco significantly
increases the risk of developing
lung cancer. Non-small cell
lung cancer (NSCLC) is
diagnosed in almost 80% of all
lung cancer patients. Despite different subtypes of
NSCLC, treatment regimens to not distinguish between subtypes. Different stages
and localization of determine treatment with surgery, radiotherapy or systemic
cytotoxic agents. Adenocarcinoma, squamous cell carcinoma and large cell
carcinoma are the three major subtypes make up 90% of all NSCLC patients.
Differences in morphology, differentiation, smoking history and genetic alterations
determine these subtypes. A new generation anti-
cancer drugs have been designed
to specifically target tumor-specific alterations such as amplifications or mutations.
Various clinical trials have shown the importance of pretreatment screening for
specific alterations that can be targeted by targeted therapies. Mutations and
amplification of the epidermal growth factor have made it an interesting target for
new drug development with tyrosine kinase inhibitors and mono-clonal antibodies as
result. The future of NSCLC treatment will be based on individualized medicine in
which molecular mechanisms underlying tumor development will be of most
importance.
Advisors/Committee Members: Lammers MD. PhD., Prof. J.W.J..
Subjects/Keywords: lung cancer; treatment; targeted therapy; non-small cell lung cancer
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APA (6th Edition):
Waal, L. M. d. (2012). Treatment of subtypes in non-small cell lung cancer. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/241663
Chicago Manual of Style (16th Edition):
Waal, L M de. “Treatment of subtypes in non-small cell lung cancer.” 2012. Masters Thesis, Universiteit Utrecht. Accessed January 27, 2021.
http://dspace.library.uu.nl:8080/handle/1874/241663.
MLA Handbook (7th Edition):
Waal, L M de. “Treatment of subtypes in non-small cell lung cancer.” 2012. Web. 27 Jan 2021.
Vancouver:
Waal LMd. Treatment of subtypes in non-small cell lung cancer. [Internet] [Masters thesis]. Universiteit Utrecht; 2012. [cited 2021 Jan 27].
Available from: http://dspace.library.uu.nl:8080/handle/1874/241663.
Council of Science Editors:
Waal LMd. Treatment of subtypes in non-small cell lung cancer. [Masters Thesis]. Universiteit Utrecht; 2012. Available from: http://dspace.library.uu.nl:8080/handle/1874/241663
University of Cambridge
25.
Barry, Philip Simon.
Exploiting a novel organotypic model of SOX2-driven early squamous lung cancer to identify potential routes to chemoprevention.
Degree: PhD, 2020, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/303261
► Lung cancer is a devastating disease and is the leading cause of cancer related death globally. Squamous cell lung cancer (SQC) accounts for around 25%…
(more)
▼ Lung cancer is a devastating disease and is the leading cause of cancer related death globally. Squamous cell lung cancer (SQC) accounts for around 25% of all lung cancer diagnoses. Better strategies for the early detection, prevention and treatment of lung cancer are urgently needed. Using a novel in vitro model of SOX2-driven early SQC I performed a screen using tool compounds and compounds in late phase clinical development for potential efficacy in chemoprevention. I combined this approach with targeted genetic ablation studies to identify/characterise targets that may be key to the progression of SOX2-driven squamous cell carcinomas. In particular I highlight an AKT isoform dependence in SQC that could be exploited in future clinical chemoprevention studies.
Subjects/Keywords: lung cancer; SOX2; squamous; AKT3; chemoprevention; squamous cell lung cancer
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APA (6th Edition):
Barry, P. S. (2020). Exploiting a novel organotypic model of SOX2-driven early squamous lung cancer to identify potential routes to chemoprevention. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/303261
Chicago Manual of Style (16th Edition):
Barry, Philip Simon. “Exploiting a novel organotypic model of SOX2-driven early squamous lung cancer to identify potential routes to chemoprevention.” 2020. Doctoral Dissertation, University of Cambridge. Accessed January 27, 2021.
https://www.repository.cam.ac.uk/handle/1810/303261.
MLA Handbook (7th Edition):
Barry, Philip Simon. “Exploiting a novel organotypic model of SOX2-driven early squamous lung cancer to identify potential routes to chemoprevention.” 2020. Web. 27 Jan 2021.
Vancouver:
Barry PS. Exploiting a novel organotypic model of SOX2-driven early squamous lung cancer to identify potential routes to chemoprevention. [Internet] [Doctoral dissertation]. University of Cambridge; 2020. [cited 2021 Jan 27].
Available from: https://www.repository.cam.ac.uk/handle/1810/303261.
Council of Science Editors:
Barry PS. Exploiting a novel organotypic model of SOX2-driven early squamous lung cancer to identify potential routes to chemoprevention. [Doctoral Dissertation]. University of Cambridge; 2020. Available from: https://www.repository.cam.ac.uk/handle/1810/303261
University of Toronto
26.
Ting Hai, Josephine Wun.
Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer.
Degree: PhD, 2014, University of Toronto
URL: http://hdl.handle.net/1807/79814
► Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Global expression profiling of patient tumours has identified hundreds of genes controlling…
(more)
▼ Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Global expression profiling of patient tumours has identified hundreds of genes controlling NSCLC progression and patient survival. Our laboratory previously identified a robust 15-gene prognostic signature predictive of NSCLC patient outcome. We hypothesized that these genes may contribute to malignant progression of lung cancer. This thesis probes the functions of three signature genes as a means to classify their expression changes as causal or responsive to NSCLC. In the first study, the signature gene L1CAM was found to promote both NSCLC metastasis and cell migration and invasion. This was supported by in silico analyses, which showed that L1CAM expression is consistently an independent prognostic factor in multiple large cohorts of NSCLC patients. The second study identified the signature gene TRIM14 as a putative NSCLC tumour suppressor. Loss of TRIM14 function increased in vitro proliferation and in vivo tumorigenicity of NSCLC cell lines. To exert its function, TRIM14 interacts with apoptosis-inducing factor possibly regulating its stability. The third study explored the efficacy of molecularly targeting prognostic biomarkers such as the signature gene MDM2 in primary tumour xenograft models of NSCLC. MDM2 inhibitors were found to effectively inhibit NSCLC tumour growth by activating the p53 tumour suppressor pathway and cell cycle arrest, confirming a role for MDM2 in the oncogenesis of NSCLC. Overall, these results demonstrate that prognostic gene signatures constructed using genomics approaches are a powerful tool to uncover genes having critical roles in lung cancer progression.
2017-11-16 00:00:00
Advisors/Committee Members: Tsao, Ming S, Medical Biophysics.
Subjects/Keywords: lung cancer; Non-small cell lung cancer; 0992
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APA (6th Edition):
Ting Hai, J. W. (2014). Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/79814
Chicago Manual of Style (16th Edition):
Ting Hai, Josephine Wun. “Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer.” 2014. Doctoral Dissertation, University of Toronto. Accessed January 27, 2021.
http://hdl.handle.net/1807/79814.
MLA Handbook (7th Edition):
Ting Hai, Josephine Wun. “Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer.” 2014. Web. 27 Jan 2021.
Vancouver:
Ting Hai JW. Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer. [Internet] [Doctoral dissertation]. University of Toronto; 2014. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1807/79814.
Council of Science Editors:
Ting Hai JW. Functional Analysis of Novel Prognostic Markers of Non-small Cell Lung Cancer. [Doctoral Dissertation]. University of Toronto; 2014. Available from: http://hdl.handle.net/1807/79814
IUPUI
27.
Krueger, Ellen F.
Development of a Patient Centered Outcome Questionnaire for Advanced Lung Cancer Patients.
Degree: 2020, IUPUI
URL: http://hdl.handle.net/1805/22685
► Indiana University-Purdue University Indianapolis (IUPUI)
Symptom research with advanced lung cancer patients has primarily focused on symptom severity, frequency, and distress; yet, little is known…
(more)
▼ Indiana University-Purdue University Indianapolis (IUPUI)
Symptom research with advanced lung cancer patients has primarily focused on symptom severity, frequency, and distress; yet, little is known about advanced lung cancer patients’ priorities and success criteria for symptom improvement. To address these gaps in the literature, this study examined these outcomes using a modified Patient Centered Outcomes Questionnaire (PCOQ), which has largely been used with adults with chronic pain. Advanced lung cancer patients (N = 102) were recruited from the Indiana University Simon Cancer Center to participate in a one-time self-report survey, including demographic and medical questionnaires, symptom treatment history, standardized measures of symptom severity and quality of life, and the modified PCOQ focused on eight common symptoms in advanced lung cancer. Cancer information was collected from medical records. My primary aim was to evaluate the construct validity of the PCOQ. As hypothesized, symptom severity ratings on the PCOQ were positively correlated with standardized assessments of the same symptoms as well as functional status. Greater severity of most symptoms on the PCOQ was also correlated with worse quality of life, and greater severity of four symptoms was correlated with having more medical comorbidities. Positive, moderate correlations were found between the severity and importance of seeing improvement in cough, fatigue, sleep problems, and pain on the PCOQ. Patients considered low levels of symptom severity to be acceptable following symptom treatment; no differences were found across the eight symptoms. Latent profile analysis identified four patient subgroups based on the importance of seeing improvement in each of the symptoms: (1) those who rated all symptoms as low in importance (n = 12); (2) those who rated bronchial symptoms and sleep problems as low in importance and all other symptoms as moderately important (n = 29); (3) those who rated nausea and emotional distress as low in importance and all other symptoms as moderately important (n = 23); and (4) those who rated all symptoms as highly important (n = 33). These subgroups were unrelated to demographic and clinical factors, except for functional status. Findings suggest that symptom severity and importance are related yet distinct aspects of the advanced lung cancer symptom experience. Furthermore, patients have heterogeneous priorities for symptom management, which has implications for tailoring treatment.
Advisors/Committee Members: Mosher, Catherine, Hirsh, Adam, McGrew, John.
Subjects/Keywords: lung cancer; patient-centered care; cancer symptom management; advanced lung cancer; patient-centered outcomes
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Manager
APA (6th Edition):
Krueger, E. F. (2020). Development of a Patient Centered Outcome Questionnaire for Advanced Lung Cancer Patients. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/22685
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):
Krueger, Ellen F. “Development of a Patient Centered Outcome Questionnaire for Advanced Lung Cancer Patients.” 2020. Thesis, IUPUI. Accessed January 27, 2021.
http://hdl.handle.net/1805/22685.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Krueger, Ellen F. “Development of a Patient Centered Outcome Questionnaire for Advanced Lung Cancer Patients.” 2020. Web. 27 Jan 2021.
Vancouver:
Krueger EF. Development of a Patient Centered Outcome Questionnaire for Advanced Lung Cancer Patients. [Internet] [Thesis]. IUPUI; 2020. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/1805/22685.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Krueger EF. Development of a Patient Centered Outcome Questionnaire for Advanced Lung Cancer Patients. [Thesis]. IUPUI; 2020. Available from: http://hdl.handle.net/1805/22685
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
28.
Yamazaki, Motohiko.
A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma : 術前CT所見と術後血清癌胎児性抗原 (CEA) の値を組み合わせると病理病期 I 期肺腺癌の再発予測能が向上する.
Degree: 博士（医学）, 2015, Niigata University / 新潟大学
URL: http://hdl.handle.net/10191/32260
► 学位の種類: 博士（医学）. 報告番号: 甲第3976号. 学位記番号: 新大院博（医）甲第622号. 学位授与年月日: 平成27年3月23日
European Journal of Radiology. 2015, 84(1), 178-184.
Objectives: To assess the prognostic value of combined evaluation of…
(more)
▼ 学位の種類: 博士（医学）. 報告番号: 甲第3976号. 学位記番号: 新大院博（医）甲第622号. 学位授与年月日: 平成27年3月23日
European Journal of Radiology. 2015, 84(1), 178-184.
Objectives: To assess the prognostic value of combined evaluation of preoperative CT findings and pre/postoperative serum carcinoembryonic antigen (CEA) levels for pathological stage I lung adenocarcinoma. Methods: This retrospective study included 250 consecutive patients who underwent complete resection for <__-3-cm pathological stage I (T1–2aN0M0) adenocarcinomas (132 men, 118 women; mean age, 67.8 years). Radiologists evaluated following CT findings: maximum tumor diameter, percentage of solid component (%solid), air bronchogram, spiculation, adjacency of bullae or interstitial pneumonia (IP) around the tumor, notch, and pleural indent. These CT findings, pre/postoperative CEA levels, age, gender, and Brinkman index were assessed by Cox proportional hazards model to determine the best prognostic model. Prognostic accuracy was examined using the area under the receiver operating characteristic curve (AUC). Results: Median follow-up period was 73.2 months. In multivariate analysis, high %solid, adjacency of bullae or IP around the tumor, and high postoperative CEA levels comprised the best combination for predicting recurrence (P < 0.05). A combination of these three findings had a greater accuracy in predicting 5-year disease-free survival than did %solid alone (AUC = 0.853 versus 0.792; P = 0.023), with a sensitivity of 85.7% and a specificity of 74.3% at the optimal threshold. The best cut-off values of %solid and postoperative CEA levels for predicting high-risk patients were >__-48% and >__-3.7 ng/mL, respectively. Conclusion: Compared to %solid alone, combined evaluation of %solid, adjacency of bullae or IP change around the tumor, and postoperative CEA levels improves recurrence prediction for stage I lung adenocarcinoma.
Subjects/Keywords: Chest CT imaging; lung adenocarcinoma; lung cancer; serum CEA levels; prognosis
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APA (6th Edition):
Yamazaki, M. (2015). A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma : 術前CT所見と術後血清癌胎児性抗原 (CEA) の値を組み合わせると病理病期 I 期肺腺癌の再発予測能が向上する. (Thesis). Niigata University / 新潟大学. Retrieved from http://hdl.handle.net/10191/32260
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):
Yamazaki, Motohiko. “A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma : 術前CT所見と術後血清癌胎児性抗原 (CEA) の値を組み合わせると病理病期 I 期肺腺癌の再発予測能が向上する.” 2015. Thesis, Niigata University / 新潟大学. Accessed January 27, 2021.
http://hdl.handle.net/10191/32260.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yamazaki, Motohiko. “A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma : 術前CT所見と術後血清癌胎児性抗原 (CEA) の値を組み合わせると病理病期 I 期肺腺癌の再発予測能が向上する.” 2015. Web. 27 Jan 2021.
Vancouver:
Yamazaki M. A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma : 術前CT所見と術後血清癌胎児性抗原 (CEA) の値を組み合わせると病理病期 I 期肺腺癌の再発予測能が向上する. [Internet] [Thesis]. Niigata University / 新潟大学; 2015. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/10191/32260.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yamazaki M. A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma : 術前CT所見と術後血清癌胎児性抗原 (CEA) の値を組み合わせると病理病期 I 期肺腺癌の再発予測能が向上する. [Thesis]. Niigata University / 新潟大学; 2015. Available from: http://hdl.handle.net/10191/32260
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Kyoto University / 京都大学
29.
Nakaoku, Takashi.
Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma : 浸潤性粘液肺腺がんの遺伝子異常.
Degree: 博士(医学), 2016, Kyoto University / 京都大学
URL: http://hdl.handle.net/2433/215443
;
http://dx.doi.org/10.14989/doctor.k19617
リポジトリの登録にあたっては、Peer reviewされた最終版のみ可能であり、その際には下記の出版社のウェブサイトのアドレスを記載することが求められる。当該論文は2014年6月の出版であり、12ヶ月を経過していることから、公開には差し支えはない。http://clincancerres.aacrjournals.org/content/20/12/3087.full
新制・課程博士
甲第19617号
医博第4124号
Subjects/Keywords: Lung Cancer; Imvasive mucinous lung adenocarcinoma; Gene rearrangement; Targeted therapy; NRG1
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APA (6th Edition):
Nakaoku, T. (2016). Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma : 浸潤性粘液肺腺がんの遺伝子異常. (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/215443 ; http://dx.doi.org/10.14989/doctor.k19617
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):
Nakaoku, Takashi. “Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma : 浸潤性粘液肺腺がんの遺伝子異常.” 2016. Thesis, Kyoto University / 京都大学. Accessed January 27, 2021.
http://hdl.handle.net/2433/215443 ; http://dx.doi.org/10.14989/doctor.k19617.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nakaoku, Takashi. “Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma : 浸潤性粘液肺腺がんの遺伝子異常.” 2016. Web. 27 Jan 2021.
Vancouver:
Nakaoku T. Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma : 浸潤性粘液肺腺がんの遺伝子異常. [Internet] [Thesis]. Kyoto University / 京都大学; 2016. [cited 2021 Jan 27].
Available from: http://hdl.handle.net/2433/215443 ; http://dx.doi.org/10.14989/doctor.k19617.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nakaoku T. Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma : 浸潤性粘液肺腺がんの遺伝子異常. [Thesis]. Kyoto University / 京都大学; 2016. Available from: http://hdl.handle.net/2433/215443 ; http://dx.doi.org/10.14989/doctor.k19617
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Louisiana State University
30.
Williams, Kendrick J.
Assessment of detection and characterization of simulated lung nodules with low-dose CT.
Degree: MS, Physical Sciences and Mathematics, 2013, Louisiana State University
URL: etd-09122013-070549
;
https://digitalcommons.lsu.edu/gradschool_theses/3320
► Purpose: The quality of a computed tomography (CT) image and the dose delivered depend upon the acquisition parameters used to acquire the CT scan. Current,…
(more)
▼ Purpose: The quality of a computed tomography (CT) image and the dose delivered depend upon the acquisition parameters used to acquire the CT scan. Current, voltage and pitch are acquisition parameters that affect the image quality. The purpose of this study was to determine the influence of current, voltage and pitch on physicians’ ability to characterize small, solid nodules with low-dose computed tomography. Methods: A database of lung scans with various acquisition parameters was compiled. A torso phantom and acrylic beads were used to simulate the lungs and nodules within the lungs. Several sizes of acrylic sphere were used to simulate different size nodules. An image visualization software was used to display the images for physicians and to assess. The physicians’ assessments were compared to known objects. The reliability of CTDI estimates reported by the CT acquisition software was verified. Results: The diameter that physician’s measured for the sphere became closer to the actual diameter of the sphere as the sphere size, tube current, and kVp increased. The pitch did not affect the physicians’ measurement of sphere size for the larger sphere as much as it did for the smaller spheres. Conclusion: We concluded that physicians are still able to judge size and shape of nodules accurately using low-dose CT. The 80 kV tube voltage proved to be an ineffective voltage for screening for lung cancer. Between the machines used there was not a substantial difference in perceived image quality when a current of 50 mA or higher was used. Based on this work, a low-dose protocol of 120 kV, 50 mA, and a pitch of 1.4 is recommended to balance patient dose and acceptable image quality.
Subjects/Keywords: Low-Dose CT; Lung Cancer Screening; Computed Tomography; Simulated lung nodules
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APA (6th Edition):
Williams, K. J. (2013). Assessment of detection and characterization of simulated lung nodules with low-dose CT. (Masters Thesis). Louisiana State University. Retrieved from etd-09122013-070549 ; https://digitalcommons.lsu.edu/gradschool_theses/3320
Chicago Manual of Style (16th Edition):
Williams, Kendrick J. “Assessment of detection and characterization of simulated lung nodules with low-dose CT.” 2013. Masters Thesis, Louisiana State University. Accessed January 27, 2021.
etd-09122013-070549 ; https://digitalcommons.lsu.edu/gradschool_theses/3320.
MLA Handbook (7th Edition):
Williams, Kendrick J. “Assessment of detection and characterization of simulated lung nodules with low-dose CT.” 2013. Web. 27 Jan 2021.
Vancouver:
Williams KJ. Assessment of detection and characterization of simulated lung nodules with low-dose CT. [Internet] [Masters thesis]. Louisiana State University; 2013. [cited 2021 Jan 27].
Available from: etd-09122013-070549 ; https://digitalcommons.lsu.edu/gradschool_theses/3320.
Council of Science Editors:
Williams KJ. Assessment of detection and characterization of simulated lung nodules with low-dose CT. [Masters Thesis]. Louisiana State University; 2013. Available from: etd-09122013-070549 ; https://digitalcommons.lsu.edu/gradschool_theses/3320
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Open Access Theses and Dissertations