You searched for subject:(Cancer therapy).
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University of Southern California
1.
Sankaranarayanan, Ishwarya.
Stable expression of human B7-H4 in a mouse mammary tumor
model as a target for cancer immunotherapy.
Degree: MS, Molecular Microbiology and Immunology, 2014, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/444516/rec/6022 
► B7‐H4 is a member of the B7 family, which is a costimulatory molecule and negatively regulates the immune response of T cells. Its mechanism of…
(more)
▼ B7‐H4 is a member of the B7 family, which is a
costimulatory molecule and negatively regulates the immune response
of T cells. Its mechanism of tumoral immune escape and therapeutic
targeting is still unknown. B7‐H4 is overly expressed in breast
cancer, ovarian
cancer, and many solid tumors and is being
investigated as a good immunotherapy target for antibodies or
antibody drug conjugates. To elucidate its immune function as well
as investigate newly developed anti‐B7‐H4 antibodies, the murine
mammary tumor cell line, 4T1, was transfected with the human B7‐H4
gene to generate a syngeneic tumor model in immuno‐competent BALB/c
mice. To facilitate the generation of a stabile cell line for in
vivo studies, 4T1 a mouse breast
cancer cell line with metastatic
potential similar to that seen in human breast
cancer, was
transfected with the pIRES‐eGFP plasmid containing an internal
ribosomal entry site of encephalomyocarditis virus (CMV), the gene
for green fluorescent protein (GFP), and the Genetecin resistant
gene for selection. The human B7‐H4 gene was first amplified from
the SKBR3 human breast
cancer cell line known to be a high
expressor of B7‐H4 and cloned into pIRES‐eGFP via the EcoRI and
BamHI restriction sites. Tumors grown on BALB/c mice with
transfected 4T1 cells were not rejected demonstrating the utility
of this approach.
Advisors/Committee Members: McMillan, Minnie (Committee Chair), Epstein, Alan L. (Committee Member), Akbari, Omid (Committee Member).
Subjects/Keywords: cancer therapy
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APA (6th Edition):
Sankaranarayanan, I. (2014). Stable expression of human B7-H4 in a mouse mammary tumor
model as a target for cancer immunotherapy. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/444516/rec/6022
Chicago Manual of Style (16th Edition):
Sankaranarayanan, Ishwarya. “Stable expression of human B7-H4 in a mouse mammary tumor
model as a target for cancer immunotherapy.” 2014. Masters Thesis, University of Southern California. Accessed January 17, 2020.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/444516/rec/6022.
MLA Handbook (7th Edition):
Sankaranarayanan, Ishwarya. “Stable expression of human B7-H4 in a mouse mammary tumor
model as a target for cancer immunotherapy.” 2014. Web. 17 Jan 2020.
Vancouver:
Sankaranarayanan I. Stable expression of human B7-H4 in a mouse mammary tumor
model as a target for cancer immunotherapy. [Internet] [Masters thesis]. University of Southern California; 2014. [cited 2020 Jan 17].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/444516/rec/6022.
Council of Science Editors:
Sankaranarayanan I. Stable expression of human B7-H4 in a mouse mammary tumor
model as a target for cancer immunotherapy. [Masters Thesis]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/444516/rec/6022
University of Otago
2.
Mazumder, Aloran.
Raloxifene along with curcumin analogue RL91, a combinational approach against hormone refractory prostate cancer
.
Degree: 2013, University of Otago
URL: http://hdl.handle.net/10523/4070
► Background: Approximately 80% of prostate cancer patients undergoing hormone therapy progress within 12-18 months to a hormone insensitive form of the disease known as hormone…
(more)
▼ Background: Approximately 80% of prostate
cancer patients undergoing hormone
therapy progress within 12-18 months to a hormone insensitive form of the disease known as hormone refractory prostate
cancer. The median survival rate is less than 12 months and traditional therapeutic agents have shown little effect on the progression of the disease. The selective estrogen receptor modulator (SERM), raloxifene has been examined in a limited phase ІІ clinical trial and showed anti-tumor properties. The current study investigated the activity of raloxifene on expression of ERα, ERβ, AR, EGFR and caveolin-1. Also the study aimed to see whether synergistic cytotoxicity could be obtained administering raloxifene in combination with the curcumin analogue RL91.
Methods: Two different hormone refractory prostate
cancer cell lines PC3 and DU-145 were used in the study. PC3 cells were specifically used to understand the role of raloxifene 10 and 15 μM on different receptors such as estrogen receptor α (ERα), estrogen receptor β (ERβ), androgen receptor (AR), epidermal growth factor receptor (EGFR) and caveolin-1. Since raloxifene is a SERM it should primarily target estrogen receptors. We wanted to determine the effect of raloxifene on different receptors. Immunocytochemistry and Western blotting was carried out to analyze the change in receptor localization and quantitative protein expression levels, respectively. To assess the synergistic potential of the combinational
therapy, raloxifene 5, 10 μM and RL91 1.5 and 2 μM were measured individually and in combination on PC3 and DU-145 using sulforhodamine B assay.
Results: Raloxifene treatment affected the localization of ERβ, EGFR, AR and caveolin-1 in PC3 cells. The drug was shown to increase the translocation of ERβ and EGFR after 6 h of treatment with a maximum difference observed after 48 h. Also, a decreased expression of ERβ and EGFR was shown following 48 h of raloxifene treatment. It also decreased the co-localization of the EGFR and caveolin-1. Apart from this, it also induced vesicle formation and accumulation of cellular content inside the cells. The cytotoxicity assay showed more cytotoxic potential of RL91 compared to raloxifene, however the combination showed synergism with more than 80 % of cell death observed for both PC3 and DU-145 cells following raloxifene 10 μM and RL91 1.5 μM treatment.
Conclusions: In HRPC, ER and EGFR mediated signaling is important for the proliferation of the cells. Raloxifene’s modulation of ERβ, EGFR and AR develops a stressed condition for the cells which decreased the proliferation. By this mechanism raloxifene enhances the cytotoxicity elicited by RL91 when administered in combination.
Advisors/Committee Members: Rosengren, Rhonda (advisor).
Subjects/Keywords: Therapy against prostate cancer;
therapy;
prostate;
cancer
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Manager
APA (6th Edition):
Mazumder, A. (2013). Raloxifene along with curcumin analogue RL91, a combinational approach against hormone refractory prostate cancer
. (Masters Thesis). University of Otago. Retrieved from http://hdl.handle.net/10523/4070
Chicago Manual of Style (16th Edition):
Mazumder, Aloran. “Raloxifene along with curcumin analogue RL91, a combinational approach against hormone refractory prostate cancer
.” 2013. Masters Thesis, University of Otago. Accessed January 17, 2020.
http://hdl.handle.net/10523/4070.
MLA Handbook (7th Edition):
Mazumder, Aloran. “Raloxifene along with curcumin analogue RL91, a combinational approach against hormone refractory prostate cancer
.” 2013. Web. 17 Jan 2020.
Vancouver:
Mazumder A. Raloxifene along with curcumin analogue RL91, a combinational approach against hormone refractory prostate cancer
. [Internet] [Masters thesis]. University of Otago; 2013. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/10523/4070.
Council of Science Editors:
Mazumder A. Raloxifene along with curcumin analogue RL91, a combinational approach against hormone refractory prostate cancer
. [Masters Thesis]. University of Otago; 2013. Available from: http://hdl.handle.net/10523/4070
Deakin University
3.
Ajji, Parminder Kaur.
Functional characterization of a novel ribosome inactivating protein from Momordica balsamina.
Degree: School of Life and Environmental Sciences, 2016, Deakin University
URL: http://hdl.handle.net/10536/DRO/DU:30103049
► This study provides an insight into the cytotoxic potential of natural and recombinant ribosome-inactivating protein (Balsamin) from Momordica balsamina. It explores the molecular mechanism of…
(more)
▼ This study provides an insight into the cytotoxic potential of natural and recombinant ribosome-inactivating protein (Balsamin) from Momordica balsamina. It explores the molecular mechanism of Balsamin-induced apoptosis in
cancer cells. The study offers far-reaching implications of exploring new balsamin targets and delivery systems for
cancer therapy.
Advisors/Committee Members: Puri, Munish, Walder, Ken, Barrow, Colin.
Subjects/Keywords: liver cancer therapy; breast cancer therapy; balsamin
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APA (6th Edition):
Ajji, P. K. (2016). Functional characterization of a novel ribosome inactivating protein from Momordica balsamina. (Thesis). Deakin University. Retrieved from http://hdl.handle.net/10536/DRO/DU:30103049
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):
Ajji, Parminder Kaur. “Functional characterization of a novel ribosome inactivating protein from Momordica balsamina.” 2016. Thesis, Deakin University. Accessed January 17, 2020.
http://hdl.handle.net/10536/DRO/DU:30103049.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ajji, Parminder Kaur. “Functional characterization of a novel ribosome inactivating protein from Momordica balsamina.” 2016. Web. 17 Jan 2020.
Vancouver:
Ajji PK. Functional characterization of a novel ribosome inactivating protein from Momordica balsamina. [Internet] [Thesis]. Deakin University; 2016. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/10536/DRO/DU:30103049.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ajji PK. Functional characterization of a novel ribosome inactivating protein from Momordica balsamina. [Thesis]. Deakin University; 2016. Available from: http://hdl.handle.net/10536/DRO/DU:30103049
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Rutgers University
4.
FENG, XING, 1987-.
Roles of SETD4 in radiation sensitivity and tumorigenesis.
Degree: PhD, Pharmacology, Cellular and Molecular, 2018, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/59084/
► The SET domain protein methyltransferases play a critical role in histone modifications and global epigenetic regulations. Recent evidence suggests that some SET domain proteins may…
(more)
▼ The SET domain protein methyltransferases play a critical role in histone modifications and global epigenetic regulations. Recent evidence suggests that some SET domain proteins may have the ability to modify non-histone proteins. The SET domain containing protein 4 (SETD4) was believed to be a non-histone methyltransferase, but no physiological substrate or biological functions of SETD4 has been identified. In this study, we constructed an inducible Setd4 knockout model and investigated the role of Setd4 in radiation sensitivity and tumorigenesis. We found that Setd4 deficient mice were significantly more resistant to radiation-induced hematopoietic syndrome than littermate wild type mice. Using several long-term bone marrow transplantation assays, we found that Setd4 deficient hematopoietic stem cells (HSCs) and progenitor cells (HPCs) have a slight in vivo growth advantage than the wild type cells, but are more sensitive to radiation. We also found that the Setd4 deficient recipient mice have an enhanced ability to engraft transplanted HSCs, suggesting an improved bone marrow niche for the Setd4 deficient animals. Using a radiation-induced thymic lymphoma model, we also found that Setd4 deletion delayed radiation-induced tumorigenesis. Collectively, our study suggests that Setd4 defect can enhance the recovery of radiation-induced bone marrow damage and suppress radiation-induced thymic lymphoma, and that Setd4 is a new gene involved in regulating bone marrow and hematopoietic functions in mice.
Advisors/Committee Members: Bunting, Samuel (chair), Shen, Zhiyuan (internal member), Denzin, Lisa (internal member), Xie, Ping (outside member), School of Graduate Studies.
Subjects/Keywords: Cancer – Gene therapy
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APA (6th Edition):
FENG, XING, 1. (2018). Roles of SETD4 in radiation sensitivity and tumorigenesis. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/59084/
Chicago Manual of Style (16th Edition):
FENG, XING, 1987-. “Roles of SETD4 in radiation sensitivity and tumorigenesis.” 2018. Doctoral Dissertation, Rutgers University. Accessed January 17, 2020.
https://rucore.libraries.rutgers.edu/rutgers-lib/59084/.
MLA Handbook (7th Edition):
FENG, XING, 1987-. “Roles of SETD4 in radiation sensitivity and tumorigenesis.” 2018. Web. 17 Jan 2020.
Vancouver:
FENG, XING 1. Roles of SETD4 in radiation sensitivity and tumorigenesis. [Internet] [Doctoral dissertation]. Rutgers University; 2018. [cited 2020 Jan 17].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/59084/.
Council of Science Editors:
FENG, XING 1. Roles of SETD4 in radiation sensitivity and tumorigenesis. [Doctoral Dissertation]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/59084/
5.
Wright, Robert Clay.
ADVANCES IN THE DEVELOPMENT OF HIF-1α-ACTIVATED PROTEIN SWITCHES FOR ENZYME PRODRUG THERAPY.
Degree: 2014, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/37975
► Prevailing approaches for developing cancer protein therapeutics focus on creating proteins that therapeutically modulate a cancer marker’s function. Such an approach limits the therapeutic mechanism…
(more)
▼ Prevailing approaches for developing
cancer protein therapeutics focus on creating proteins that therapeutically modulate a
cancer marker’s function. Such an approach limits the therapeutic mechanism to those that naturally arise from modulation of the
cancer marker and precludes the use of
cancer markers for which therapeutic modulation is not feasible. Furthermore, many potential protein therapies lack the desired
cancer targeting. The ability to link recognition of any
cancer marker with activation of any desired therapeutic function would enormously expand the number of possible protein therapeutics. We have previously engineered a switchable prodrug-activating enzyme that selectively kills human
cancer cells that accumulate the
cancer marker hypoxia-inducible factor 1α (HIF-1α). This HIF-1α-activated enzyme switch (Haps59) was created by fusing the prodrug-converting enzyme yeast cytosine deaminase (yCD) and the CH1 domain of the p300 protein, which binds HIF-1α.
Haps59 autonomously increases its ability to convert the prodrug 5-fluorcytosine (5FC) into the chemotherapeutic 5-fluorouracil (5FU) in a HIF-1α-dependent manner, rendering colon and breast
cancer cells more susceptible to the prodrug. However, the difference in 5FC sensitivity between the presence and absence of HIF-1α was not as large as desired. Using a variety of mutagenesis methods, followed by a two-tiered genetic selection for improved switches, we have identified new HIF-1α-activated enzymes that confer E. coli with modest increases in HIF-1α-dependent 5FC toxicity. However, the current bottleneck in further translation of HIF-1α-activated protein switches is screening potential switch candidates in mammalian cells. To accommodate higher throughput, we explored the use of Flp recombinase-mediated isogenic integration. While initial results in this system are promising, these experiments also brought to light the disadvantageous promiscuous binding activity of the CH1 domain,
which we further confirmed in E. coli. This promiscuous binding and subsequent off-target activation needs to be examined under normal physiological conditions to pinpoint off-target activity in these potential therapeutics. With relevant aberrant activators identified, further directed evolution can be used to improve the
cancer specificity of HIF-1α-activated protein switches.
Advisors/Committee Members: Townsend, Craig A (advisor).
Subjects/Keywords: Enzyme Prodrug Therapy; Protein Engineering; Cancer Therapy
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APA (6th Edition):
Wright, R. C. (2014). ADVANCES IN THE DEVELOPMENT OF HIF-1α-ACTIVATED PROTEIN SWITCHES FOR ENZYME PRODRUG THERAPY. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37975
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):
Wright, Robert Clay. “ADVANCES IN THE DEVELOPMENT OF HIF-1α-ACTIVATED PROTEIN SWITCHES FOR ENZYME PRODRUG THERAPY.” 2014. Thesis, Johns Hopkins University. Accessed January 17, 2020.
http://jhir.library.jhu.edu/handle/1774.2/37975.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wright, Robert Clay. “ADVANCES IN THE DEVELOPMENT OF HIF-1α-ACTIVATED PROTEIN SWITCHES FOR ENZYME PRODRUG THERAPY.” 2014. Web. 17 Jan 2020.
Vancouver:
Wright RC. ADVANCES IN THE DEVELOPMENT OF HIF-1α-ACTIVATED PROTEIN SWITCHES FOR ENZYME PRODRUG THERAPY. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2020 Jan 17].
Available from: http://jhir.library.jhu.edu/handle/1774.2/37975.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wright RC. ADVANCES IN THE DEVELOPMENT OF HIF-1α-ACTIVATED PROTEIN SWITCHES FOR ENZYME PRODRUG THERAPY. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37975
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Georgia Tech
6.
Mackey, Megan A.
Gold nanoparticles in some chemical and photothermal applications of cancer therapy.
Degree: PhD, Chemistry and Biochemistry, 2013, Georgia Tech
URL: http://hdl.handle.net/1853/52934
► Gold nanoparticles exhibit an array of properties, both intrinsic (chemical) and extrinsic (photothermal), that can be exploited for their use in cancer therapeutics. Owing to…
(more)
▼ Gold nanoparticles exhibit an array of properties, both intrinsic (chemical) and extrinsic (photothermal), that can be exploited for their use in
cancer therapeutics. Owing to their size and ease with which they can be functionalized with various ligands, gold nanoparticles represent a class of highly functional biomedically relevant nanostructures. Here, we explore the use of gold nanoparticles as intrinsic (chemical) antineoplastic agents, with their ability to cause DNA damage and cytokinesis arrest, to induce apoptosis in a metallic composition-dependent manner, as well as their ability to enhance sensitivity to chemotherapy by regulation of the cell cycle. The extrinsic (photothermal) properties of gold nanoparticles are also examined, in detail, through both theoretical and experimental assessment, for their use as photothermal contrast agents in vitro. Based on this assessment, the gold nanoparticles are tested in the plasmonic photothermal
therapy of head and neck
cancer in a mouse model.
Advisors/Committee Members: El-Sayed, Mostafa A. (advisor), Schmidt-Krey, Ingeborg (committee member), Barry, Bridgette A. (committee member), Oyelere, Adegboyega K. (committee member), Payne, Christine K. (committee member).
Subjects/Keywords: Gold nanopartices; Cancer therapy; Photothermal therapy
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APA (6th Edition):
Mackey, M. A. (2013). Gold nanoparticles in some chemical and photothermal applications of cancer therapy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/52934
Chicago Manual of Style (16th Edition):
Mackey, Megan A. “Gold nanoparticles in some chemical and photothermal applications of cancer therapy.” 2013. Doctoral Dissertation, Georgia Tech. Accessed January 17, 2020.
http://hdl.handle.net/1853/52934.
MLA Handbook (7th Edition):
Mackey, Megan A. “Gold nanoparticles in some chemical and photothermal applications of cancer therapy.” 2013. Web. 17 Jan 2020.
Vancouver:
Mackey MA. Gold nanoparticles in some chemical and photothermal applications of cancer therapy. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/1853/52934.
Council of Science Editors:
Mackey MA. Gold nanoparticles in some chemical and photothermal applications of cancer therapy. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/52934
University of Alberta
7.
Keuling, Angela.
Characterization of the response of melanoma cell lines to
inhibition of anti-apoptotic Bcl-2 proteins.
Degree: PhD, Medical Sciences - Medical Genetics, 2010, University of Alberta
URL: https://era.library.ualberta.ca/files/3t945r78j
► Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma…
(more)
▼ Malignant melanoma is resistant to almost all
conventional forms of chemotherapy. Recent evidence suggests that
anti-apoptotic proteins of the Bcl-2 family are overexpressed in
melanoma and may contribute to melanoma’s striking resistance to
apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and
Bcl-w, has demonstrated efficacy in several forms of cancer.
However, overexpression of Mcl-1, a frequent observance in
melanoma, is known to confer ABT-737 resistance. My results
demonstrate that the combination of ABT-737 and RNA silencing of
Mcl-1 induces significant cell death in six different melanoma cell
lines, representing a potential new therapeutic strategy. I show
that the apoptotic response to the combination treatment involves
both the intrinsic pathway and a death receptor-independent role
for extrinsic pathway proteins. The combination treatment also
induces a number of gene expression changes as assessed by cDNA
microarray and follow-up analyses. Based on the results of the
array, I investigated the effects of inhibition of MAPK proteins
combined with ABT-737 and/or Mcl-1 knockdown. I found that the
combination of a p38 MAPK inhibitor and ABT-737 strongly and
synergistically induces apoptosis in melanoma cell lines, thus
suggesting a second novel treatment combination with potential for
melanoma therapy. Finally, I provide novel evidence that Bcl-2
family member PUMA is cleaved in a caspase-dependent fashion during
apoptosis and may play a role in treatment response. Currently,
there are no effective treatments for metastatic melanoma. My
findings describe two potential combination therapies for melanoma
as well as provide novel evidence as to the mechanisms involved in
treatment response.
Subjects/Keywords: apoptosis; cancer therapy; melanoma
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APA ·
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APA (6th Edition):
Keuling, A. (2010). Characterization of the response of melanoma cell lines to
inhibition of anti-apoptotic Bcl-2 proteins. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/3t945r78j
Chicago Manual of Style (16th Edition):
Keuling, Angela. “Characterization of the response of melanoma cell lines to
inhibition of anti-apoptotic Bcl-2 proteins.” 2010. Doctoral Dissertation, University of Alberta. Accessed January 17, 2020.
https://era.library.ualberta.ca/files/3t945r78j.
MLA Handbook (7th Edition):
Keuling, Angela. “Characterization of the response of melanoma cell lines to
inhibition of anti-apoptotic Bcl-2 proteins.” 2010. Web. 17 Jan 2020.
Vancouver:
Keuling A. Characterization of the response of melanoma cell lines to
inhibition of anti-apoptotic Bcl-2 proteins. [Internet] [Doctoral dissertation]. University of Alberta; 2010. [cited 2020 Jan 17].
Available from: https://era.library.ualberta.ca/files/3t945r78j.
Council of Science Editors:
Keuling A. Characterization of the response of melanoma cell lines to
inhibition of anti-apoptotic Bcl-2 proteins. [Doctoral Dissertation]. University of Alberta; 2010. Available from: https://era.library.ualberta.ca/files/3t945r78j
8.
Walker, David.
CREDENTIALING THE DNA METHYLATION MAINTENANCE PROTEIN UHRF1 AS A TARGET FOR ANTICANCER THERAPY.
Degree: 2014, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/37192
► Cancer is a disease of genome alterations that drive uncontrolled growth. The most challenging aspect of cancer treatment is that there are many avenues to…
(more)
▼ Cancer is a disease of genome alterations that drive uncontrolled growth. The most challenging aspect of
cancer treatment is that there are many avenues to enable proliferation within the cell, including alterations to epigenetic elements. DNA methylation—a methyl modification on the 5-carbon of cytosine bases—has been pinpointed to be one of these avenues, and as such is an option for targeted
therapy. DNA methylation at the promoter regions of genes can silence their transcription, and normally-silenced genes that are hypomethylated can be re-expressed. Current approved
cancer therapies targeting DNA methylation focus on inhibiting DNA methyltransferases, enzymes responsible for maintaining DNA methylation during division. These therapies, which are effective at reducing methylation levels on DNA globally and at tumor suppressor genes, come at a cost: they are nucleoside analogs that exhibit serious toxicities. The central hypothesis for this thesis is that another
DNA methylation maintenance protein, ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is an attractive candidate for anticancer
therapy. UHRF1 directly interacts with DNMT1 and is thought of as a “helper” molecule that recruits DNMTs to newly synthesized DNA. DNA is methylated symmetrically on both strands, but during replication new copies of DNA contain only one strand with the proper methylation information; this so-called hemimethylated state is the target for the Set- and RING-Associated (SRA) domain of UHRF1, which binds this hemimethylated DNA and allows UHRF1 to recruit the DNA methyltransferase machinery to maintain methylation on the newly synthesized strand. To address our hypothesis, we have developed a suite of molecular tools to study the impact of removing UHRF1 on cellular growth, DNA methylation patterns, gene expression and survivability in vitro. We have developed a mouse model for heterozygous deletion of UHRF1 in vivo. We have successfully
implemented a UHRF1 inhibitor assay to use on small molecule libraries to identify potential inhibitors. We show that UHRF1 is overexpressed in
cancer cell lines and tissue, and when knocked down, reduces growth and survival. We also demonstrate that UHRF1 is necessary for global and local methylation, and that methylation loss due to lower UHRF1 levels results in re-expression of silenced genes. Our mouse model of UHRF1 deletion shows that it is necessary for tumorigenesis in the APCmin model. Finally, we determine that anthracycline derivatives like mitoxantrone and doxorubicin interfere with UHRF1 binding DNA, decrease global methylation in cells and synergize with decitabine in cell killing. Synthesizing these results, we believe that UHRF1 is a viable target for
cancer treatment, and effectively inhibiting it can enhance approved DNA methylation chemotherapies for better
cancer control.
Advisors/Committee Members: Nelson, William G (advisor).
Subjects/Keywords: UHRF1;
cancer;
epigenetics;
epigenetic therapy
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Manager
APA (6th Edition):
Walker, D. (2014). CREDENTIALING THE DNA METHYLATION MAINTENANCE PROTEIN UHRF1 AS A TARGET FOR ANTICANCER THERAPY. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37192
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):
Walker, David. “CREDENTIALING THE DNA METHYLATION MAINTENANCE PROTEIN UHRF1 AS A TARGET FOR ANTICANCER THERAPY.” 2014. Thesis, Johns Hopkins University. Accessed January 17, 2020.
http://jhir.library.jhu.edu/handle/1774.2/37192.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Walker, David. “CREDENTIALING THE DNA METHYLATION MAINTENANCE PROTEIN UHRF1 AS A TARGET FOR ANTICANCER THERAPY.” 2014. Web. 17 Jan 2020.
Vancouver:
Walker D. CREDENTIALING THE DNA METHYLATION MAINTENANCE PROTEIN UHRF1 AS A TARGET FOR ANTICANCER THERAPY. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2020 Jan 17].
Available from: http://jhir.library.jhu.edu/handle/1774.2/37192.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Walker D. CREDENTIALING THE DNA METHYLATION MAINTENANCE PROTEIN UHRF1 AS A TARGET FOR ANTICANCER THERAPY. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37192
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Hong Kong
9.
Pon, Kwai-ling.
My wonderful life: developing a game based intervention
for patients with advanced cancer.
Degree: PhD, 2009, University of Hong Kong
URL: Pon,
K.
[潘桂玲].
(2009).
My
wonderful
life
:
developing
a
game
based
intervention
for
patients
with
advanced
cancer.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b4475146
;
http://dx.doi.org/10.5353/th_b4475146
;
http://hdl.handle.net/10722/130901
published_or_final_version
Social Work and Social
Administration
Doctoral
Doctor of Philosophy
Advisors/Committee Members: Chow, AYM, Chan, CLW.Subjects/Keywords: Play therapy.; Cancer - Psychological aspects.
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APA (6th Edition):
Pon, K. (2009). My wonderful life: developing a game based intervention
for patients with advanced cancer. (Doctoral Dissertation). University of Hong Kong. Retrieved from Pon, K. [潘桂玲]. (2009). My wonderful life : developing a game based intervention for patients with advanced cancer. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4475146 ; http://dx.doi.org/10.5353/th_b4475146 ; http://hdl.handle.net/10722/130901
Chicago Manual of Style (16th Edition):
Pon, Kwai-ling. “My wonderful life: developing a game based intervention
for patients with advanced cancer.” 2009. Doctoral Dissertation, University of Hong Kong. Accessed January 17, 2020.
Pon, K. [潘桂玲]. (2009). My wonderful life : developing a game based intervention for patients with advanced cancer. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4475146 ; http://dx.doi.org/10.5353/th_b4475146 ; http://hdl.handle.net/10722/130901.
MLA Handbook (7th Edition):
Pon, Kwai-ling. “My wonderful life: developing a game based intervention
for patients with advanced cancer.” 2009. Web. 17 Jan 2020.
Vancouver:
Pon K. My wonderful life: developing a game based intervention
for patients with advanced cancer. [Internet] [Doctoral dissertation]. University of Hong Kong; 2009. [cited 2020 Jan 17].
Available from: Pon, K. [潘桂玲]. (2009). My wonderful life : developing a game based intervention for patients with advanced cancer. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4475146 ; http://dx.doi.org/10.5353/th_b4475146 ; http://hdl.handle.net/10722/130901.
Council of Science Editors:
Pon K. My wonderful life: developing a game based intervention
for patients with advanced cancer. [Doctoral Dissertation]. University of Hong Kong; 2009. Available from: Pon, K. [潘桂玲]. (2009). My wonderful life : developing a game based intervention for patients with advanced cancer. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4475146 ; http://dx.doi.org/10.5353/th_b4475146 ; http://hdl.handle.net/10722/130901
10.
Servedio, Danielle Lauren.
Cancer Patients' Perception of Body Image: A Visual Exploration.
Degree: MA, Marital and Family Therapy, 2012, Loyola Marymount University
URL: http://digitalcommons.lmu.edu/etd/111
► This study explored the impact and trauma that a cancer diagnosis and cancer treatment can have on a women’s image and experience of her…
(more)
▼ This study explored the impact and trauma that a
cancer diagnosis and
cancer treatment can have on a women’s image and experience of her body. Focus group methodology was part of the qualitative art-based research approach. Since the research was focused on body image, the participants were asked to create art based on their experience of their body before and after
cancer treatment. Content analysis was applied to the transcripts of the focus group sessio n to consider themes. The clusters were then correlated with the imagery in the participants’ artwork. The study results suggest that women who have undergone medical treatment for
cancer have an altered view of their body image including fragmentation of the body, scarring and disfigurement, censoring of the body and feeling less feminine. The study asserts that the art process and discussion, in a therapeutic setting, provided a supportive environment for
cancer patients to discuss sensitive information about their perspectives of their body, diagnosis and treatment.
Advisors/Committee Members: Paige Asawa.
Subjects/Keywords: Cancer; Body Image; Art therapy
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APA (6th Edition):
Servedio, D. L. (2012). Cancer Patients' Perception of Body Image: A Visual Exploration. (Masters Thesis). Loyola Marymount University. Retrieved from http://digitalcommons.lmu.edu/etd/111
Chicago Manual of Style (16th Edition):
Servedio, Danielle Lauren. “Cancer Patients' Perception of Body Image: A Visual Exploration.” 2012. Masters Thesis, Loyola Marymount University. Accessed January 17, 2020.
http://digitalcommons.lmu.edu/etd/111.
MLA Handbook (7th Edition):
Servedio, Danielle Lauren. “Cancer Patients' Perception of Body Image: A Visual Exploration.” 2012. Web. 17 Jan 2020.
Vancouver:
Servedio DL. Cancer Patients' Perception of Body Image: A Visual Exploration. [Internet] [Masters thesis]. Loyola Marymount University; 2012. [cited 2020 Jan 17].
Available from: http://digitalcommons.lmu.edu/etd/111.
Council of Science Editors:
Servedio DL. Cancer Patients' Perception of Body Image: A Visual Exploration. [Masters Thesis]. Loyola Marymount University; 2012. Available from: http://digitalcommons.lmu.edu/etd/111
University of Rochester
11.
Stripay, Jennifer L.
Targeting a Network of Cancer Control Nodes through
Rescue of c-Cbl; A Novel Therapeutic Approach for Glioblastoma
Multiforme.
Degree: PhD, 2016, University of Rochester
URL: http://hdl.handle.net/1802/31636
► Glioblastoma multiforme is the most common primary brain tumor in adults, the most malignant of all intracranial tumors, and is associated with inevitable recurrence and…
(more)
▼ Glioblastoma multiforme is the most common primary
brain tumor in adults, the most malignant of all intracranial
tumors, and is associated with inevitable recurrence and 15 month
mean survival despite multimodal therapy. The majority of GBM
tumors maintain heterogeneous amplifications (many in the absence
of genetic mutation) in receptor tyrosine kinases (RTKs), which are
mediators of growth factor signaling. Our lab has discovered that
control over RTK levels in normal CNS progenitors is maintained by
the Redox/Fyn/c-Cbl (RFC) pathway whereby increased oxidative state
results in activation of the E3 ubiquitin ligase c-Cbl and the
subsequent internalization and degradation of target RTKs. RFC
signaling is disrupted in GBM due to a physical sequestration of
c-Cbl, preventing pro-oxidative chemotherapeutics from reducing
pro-survival signaling through EGFR, PDGFRα, etc. Using a
triangulating drug screen, we identified candidate c-Cbl restoring
agents (CRAs) from a library of FDA-approved small molecules based
on their ability to reduce signaling downstream of c-Cbl-targeted
RTKs. Considering clinically relevant criteria, we focused our
investigation on Maprotiline (MPT), a generic, tetracyclic
antidepressant. We discovered that MPT facilitated activation of
RFC signaling and restored functional activity of c-Cbl. Rescue of
c-Cbl resulted in distinct downstream effects of protein
degradation and transcriptional modulation of a network of cancer
control nodes. This translated into potent effects on GBM cell
viability and tumor initiation potential. Ultimately, this approach
was able to inhibit tumor progression and extend survival in an
animal model of GBM, supporting its clinical utility. Our work
supports the hypothesis that c-Cbl is a critical rheostat and
higher level regulator in GBM that integrates multiple nodes of
cancer control and that pharmacological rescue of c-Cbl represents
a potentially powerful therapeutic approach for this
disease.
Subjects/Keywords: Cancer; cbl; Glioblastoma; Redox; Therapy
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APA (6th Edition):
Stripay, J. L. (2016). Targeting a Network of Cancer Control Nodes through
Rescue of c-Cbl; A Novel Therapeutic Approach for Glioblastoma
Multiforme. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/31636
Chicago Manual of Style (16th Edition):
Stripay, Jennifer L. “Targeting a Network of Cancer Control Nodes through
Rescue of c-Cbl; A Novel Therapeutic Approach for Glioblastoma
Multiforme.” 2016. Doctoral Dissertation, University of Rochester. Accessed January 17, 2020.
http://hdl.handle.net/1802/31636.
MLA Handbook (7th Edition):
Stripay, Jennifer L. “Targeting a Network of Cancer Control Nodes through
Rescue of c-Cbl; A Novel Therapeutic Approach for Glioblastoma
Multiforme.” 2016. Web. 17 Jan 2020.
Vancouver:
Stripay JL. Targeting a Network of Cancer Control Nodes through
Rescue of c-Cbl; A Novel Therapeutic Approach for Glioblastoma
Multiforme. [Internet] [Doctoral dissertation]. University of Rochester; 2016. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/1802/31636.
Council of Science Editors:
Stripay JL. Targeting a Network of Cancer Control Nodes through
Rescue of c-Cbl; A Novel Therapeutic Approach for Glioblastoma
Multiforme. [Doctoral Dissertation]. University of Rochester; 2016. Available from: http://hdl.handle.net/1802/31636
Universiteit Utrecht
12.
Tenhagen, M.
FGFRs in breast cancer: expression, downstream effects and possible drug targets.
Degree: 2012, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/220167
► In the search of new drugs to treat cancer patients, many targeted therapies are being developed. Fibroblast growth factor receptors (FGFRs) are one of the…
(more)
▼ In the search of new drugs to treat
cancer patients, many targeted therapies are being developed. Fibroblast growth factor receptors (FGFRs) are one of the many molecules that are currently under investigation for their potential as a drug target in breast
cancer patients. These receptor tyrosine kinases play a major role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. In breast
cancer patients, several subgroups of patients have been identified to harbor genetic aberrations in FGFRs. These genetic aberrations include amplifications of FGFR1, -2 and -4, and mutations in FGFR2 and -4. Multiple in vitro and in vivo models have partly elucidated the molecular implications of these different genetic aberrations on the characteristics of the tumors. Based on these results several drug targets have been suggested. For some of these targets drugs have already been developed, which are currently being tested in in vitro and in vivo settings. Future experiments will have to be performed in order to further clarify the molecular implications of the genetic aberrations, to develop and test drugs but also to identify the subgroup of patients that will benefit from these newly developed therapies.
Advisors/Committee Members: P.J. van Diest, Prof. Dr..
Subjects/Keywords: FGFR; breast cancer, targeted therapy
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APA (6th Edition):
Tenhagen, M. (2012). FGFRs in breast cancer: expression, downstream effects and possible drug targets. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/220167
Chicago Manual of Style (16th Edition):
Tenhagen, M. “FGFRs in breast cancer: expression, downstream effects and possible drug targets.” 2012. Masters Thesis, Universiteit Utrecht. Accessed January 17, 2020.
http://dspace.library.uu.nl:8080/handle/1874/220167.
MLA Handbook (7th Edition):
Tenhagen, M. “FGFRs in breast cancer: expression, downstream effects and possible drug targets.” 2012. Web. 17 Jan 2020.
Vancouver:
Tenhagen M. FGFRs in breast cancer: expression, downstream effects and possible drug targets. [Internet] [Masters thesis]. Universiteit Utrecht; 2012. [cited 2020 Jan 17].
Available from: http://dspace.library.uu.nl:8080/handle/1874/220167.
Council of Science Editors:
Tenhagen M. FGFRs in breast cancer: expression, downstream effects and possible drug targets. [Masters Thesis]. Universiteit Utrecht; 2012. Available from: http://dspace.library.uu.nl:8080/handle/1874/220167
Penn State University
13.
Yao, Nengliang.
Radiation Therapy For Early Stage Breast Cancer After
Breast-conserving Surgery.
Degree: PhD, Health Policy and Administration, 2013, Penn State University
URL: https://etda.libraries.psu.edu/catalog/17428
► Background: Whole breast irradiation (WBI) has been recommended after breast-conserving surgery (BCS) in practice guidelines for definitive local therapy of early stage breast cancers since…
(more)
▼ Background: Whole breast irradiation (WBI) has been
recommended after breast-conserving surgery (BCS) in practice
guidelines for definitive local therapy of early stage breast
cancers since 1990, in light of evidence that BCS without radiation
is associated with higher local recurrence rates and higher
mortality risk. Accelerated partial breast irradiation (APBI) is an
alternative to WBI, which significantly decreases the number of
patient visits. In contrast to 16-36 doses of radiotherapy in WBI,
APBI usually involves twice-daily treatments over 4-5 days. Three
important issues related to BCS-related radiation therapy are the
focus of this dissertation. First, factors underlying regional
disparities in the receipt of radiation after BCS are not well
understood. The second issue relates to a knowledge gap about the
effect of treatment features on the probability of choosing a
treatment among different alternatives. The third issue is the
increasing use of brachytherapy APBI among early stage breast
cancer patients without conclusive population-based evidence of
clinical effectiveness. Objectives: This dissertation includes
three related studies that each address a key question related to
radiation therapy for early stage breast cancer: (1) What
mechanisms underlie geographic variation in the omission of
radiation therapy after BCS? (2) What are the effects of treatment
characteristics on the probabilities of choosing various
alternative local therapies for early stage breast cancer? and (3)
What is the comparative effectiveness of brachytherapy ABPI versus
WBI among elderly women after BCS? Methods: This dissertation
analyzes data from SEER, SEER-Medicare, the Area Resource File,
Medicare Local Coverage Determination database, and Census files.
Cancer registry codes and Medicare claims codes were used to
identify the study cohort and diagnosis and treatment information.
Spatial exploratory data analysis, logistic regression, nested
logit modeling, log-rank tests, Cox proportional hazards modeling,
and instrumental variable analyses were used to address the
research questions. Findings: The first study found that
metropolitan patients living in counties that have WBI, AAPBI, or
both services are more likely to omit radiation after BCS than
other patients living in counties without radiation therapy
facilities. Study 2 found that treatment alternatives with longer
treatment and recovery times and longer travel distances are
associated with decreased probability of being chosen. Alternatives
recommended by guidelines and covered by Medicare are associated
with increased probabilities of being chosen. Study 3 found that
the risk of death in patients treated with APBI-Brachy was not
significantly different from patients treated with WBI. Factors
independently associated with an increased risk of death included
older age, invasive cancer, tumor size greater than 2 cm, lymph
node involvement, ductal histology, negative estrogen receptor
status, undifferentiated tumor, the existence of comorbid
conditions, and living in a…
Subjects/Keywords: Radiation Therapy; Breast Cancer
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APA ·
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MLA ·
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Export
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Manager
APA (6th Edition):
Yao, N. (2013). Radiation Therapy For Early Stage Breast Cancer After
Breast-conserving Surgery. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/17428
Chicago Manual of Style (16th Edition):
Yao, Nengliang. “Radiation Therapy For Early Stage Breast Cancer After
Breast-conserving Surgery.” 2013. Doctoral Dissertation, Penn State University. Accessed January 17, 2020.
https://etda.libraries.psu.edu/catalog/17428.
MLA Handbook (7th Edition):
Yao, Nengliang. “Radiation Therapy For Early Stage Breast Cancer After
Breast-conserving Surgery.” 2013. Web. 17 Jan 2020.
Vancouver:
Yao N. Radiation Therapy For Early Stage Breast Cancer After
Breast-conserving Surgery. [Internet] [Doctoral dissertation]. Penn State University; 2013. [cited 2020 Jan 17].
Available from: https://etda.libraries.psu.edu/catalog/17428.
Council of Science Editors:
Yao N. Radiation Therapy For Early Stage Breast Cancer After
Breast-conserving Surgery. [Doctoral Dissertation]. Penn State University; 2013. Available from: https://etda.libraries.psu.edu/catalog/17428
Université Catholique de Louvain
14.
Barragan Montero, Ana Maria.
Robust, accurate and patient-specific treatment planning for proton therapy.
Degree: 2017, Université Catholique de Louvain
URL: http://hdl.handle.net/2078.1/189076
► The survival statistics for cancer patients treated with radiation therapy using photon beams show that many treatments fail due to poor tumour local control (TLC).…
(more)
▼ The survival statistics for cancer patients treated with radiation therapy using photon beams show that many treatments fail due to poor tumour local control (TLC). A potential solution would be to increase the target dose, but this often entails high toxicity in the nearby healthy tissue. Unlike photons, protons release most of their energy at the end of their path (the so-called Bragg peak), reducing the dose to healthy tissue, which might be the key for safe dose escalation. Moreover, functional images can reveal spatial heterogeneity in the tumor radioresistance pattern and therefore allow for improved targeting (dose painting) and possibly enhanced TLC. In this context, special care must be taken to accurately model the possible uncertainties in the position of the Bragg peak, since they can strongly deteriorate treatment quality, especially in very heterogeneous dose distributions as in dose painting plans. In this thesis, we investigated the use of the most advanced techniques, such as Monte Carlo dose calculation and robust optimization, to ensure accurate and robust planning for (dose painted) proton therapy treatments.
(BIFA - Sciences biomédicales et pharmaceutiques) – UCL, 2017
Advisors/Committee Members: UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - Faculté de pharmacie et des sciences biomédicales, Lee, John Aldo, Sterpin, Edmond, Lecouvet, Frédéric, Geets, Xavier, Orban de Xivry, Jonathan, Verellen, Dirk, Oelfke, Uwe, Reynaert, Nick.
Subjects/Keywords: Proton therapy; Cancer treatment planning
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APA (6th Edition):
Barragan Montero, A. M. (2017). Robust, accurate and patient-specific treatment planning for proton therapy. (Thesis). Université Catholique de Louvain. Retrieved from http://hdl.handle.net/2078.1/189076
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):
Barragan Montero, Ana Maria. “Robust, accurate and patient-specific treatment planning for proton therapy.” 2017. Thesis, Université Catholique de Louvain. Accessed January 17, 2020.
http://hdl.handle.net/2078.1/189076.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Barragan Montero, Ana Maria. “Robust, accurate and patient-specific treatment planning for proton therapy.” 2017. Web. 17 Jan 2020.
Vancouver:
Barragan Montero AM. Robust, accurate and patient-specific treatment planning for proton therapy. [Internet] [Thesis]. Université Catholique de Louvain; 2017. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/2078.1/189076.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Barragan Montero AM. Robust, accurate and patient-specific treatment planning for proton therapy. [Thesis]. Université Catholique de Louvain; 2017. Available from: http://hdl.handle.net/2078.1/189076
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Vanderbilt University
15.
Meador, Catherine Belle.
Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma.
Degree: PhD, Cancer Biology, 2015, Vanderbilt University
URL: http://etd.library.vanderbilt.edu/available/etd-07202015-172236/
;
► 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, âsecond-lineâ acquired resistance to A+C and AZD9291, after âfirst-lineâ 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), Rebecca Cook (chair), William Pao (committee member).
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://etd.library.vanderbilt.edu/available/etd-07202015-172236/ ;
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 17, 2020.
http://etd.library.vanderbilt.edu/available/etd-07202015-172236/ ;.
MLA Handbook (7th Edition):
Meador, Catherine Belle. “Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma.” 2015. Web. 17 Jan 2020.
Vancouver:
Meador CB. Optimizing the sequence of targeted therapy in EGFR-mutant lung adenocarcinoma. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2020 Jan 17].
Available from: http://etd.library.vanderbilt.edu/available/etd-07202015-172236/ ;.
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://etd.library.vanderbilt.edu/available/etd-07202015-172236/ ;
University of Waterloo
16.
Zhang, Qinrong.
A Novel Combination Therapy of Cisplatin with a Molecular Promoter for Cancer Treatment.
Degree: 2017, University of Waterloo
URL: http://hdl.handle.net/10012/11272
► Cisplatin is the first and most widely used platinum-based chemotherapy drug and is the cornerstone agent in treating a broad spectrum of cancers, including ovarian…
(more)
▼ Cisplatin is the first and most widely used platinum-based chemotherapy drug and is the cornerstone agent in treating a broad spectrum of cancers, including ovarian cancer, testicular cancer, cervical cancer, bladder cancer, lung cancer, head and neck cancer, lymphoma, and brain tumors. It is one of the few curative anti-cancer agents; however, its clinical application is often limited by severe toxic side effects and resistance possessed by some cancers.
Our group has recently, through the femtomedicine approach, unraveled a new molecular mechanism of Cisplatin. It has been found that Cisplatin is extremely effective for the dissociative electron transfer (DET) reaction with weakly-bound electrons to produce reactive radicals that cause DNA strand breaks, apoptosis, and final clonogenic cell kill.
Based on this DET mechanism, it is proposed that Cisplatin may be administered in combination with a biological electron donor to enhance its chemotherapeutic efficacy. We have tried a few combinations of Cisplatin and electron-donating compounds. In this thesis, we show results of the combination: Cisplatin and Rhodamine-B, the one with the greatest potential as demonstrated in both in vitro assays and in vivo xenograft mouse cancer models. This thesis begins with an introduction to cancer and cancer therapies in Chapter 1, where the theory, objective, and scope of this thesis are introduced. Chapter 2 focuses on some new understandings of Cisplatin-induced DNA damage. In vitro and in vivo experiment results on the effectiveness of the combination of Cisplatin and Rhodamine-B are presented in Chapter 3 and Chapter 4, respectively. In Chapter 5, time-resolved femtosecond laser spectroscopic studies on the reaction between Cisplatin and Rhodamine-B are shown. Chapter 6 as the last Chapter summarizes results obtained in this project and proposes some possible future research.
In vitro experiments confirm the potential of this proposed combination of Cisplatin and Rhodamine-B to treat cancer. From cell survival tests, by applying MTT assays and clonogenic assays, it has been shown that our proposed combination significantly enhances the cell-killing efficacy in cancer cells; but surprisingly, not in normal cells. Besides, plasmid DNA gel electrophoresis and γ-H2AX staining in treated cells indicate that more double-strand breaks can be induced using our combination, compared to Cisplatin only. In addition, measurements on Caspase 3/7 activation and Annexin V-FITC labeling flow cytometry experiments clearly show a significant enhancement in the population of apoptotic cells using our combination. To further verify the effectiveness of the combination of Cisplatin and Rhodamine-B, in vivo xenograft mouse models have been developed. Our combination greatly enhances the tumor growth inhibition and even tumor shrinkage in three different mouse models. Acute toxicity analysis and body weight measurements do not show additional side effects induced by the addition of Rhodamine-B. Lastly, spectroscopic measurements…
Subjects/Keywords: Cancer; Combination Therapy; Cisplatin
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APA (6th Edition):
Zhang, Q. (2017). A Novel Combination Therapy of Cisplatin with a Molecular Promoter for Cancer Treatment. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/11272
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):
Zhang, Qinrong. “A Novel Combination Therapy of Cisplatin with a Molecular Promoter for Cancer Treatment.” 2017. Thesis, University of Waterloo. Accessed January 17, 2020.
http://hdl.handle.net/10012/11272.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhang, Qinrong. “A Novel Combination Therapy of Cisplatin with a Molecular Promoter for Cancer Treatment.” 2017. Web. 17 Jan 2020.
Vancouver:
Zhang Q. A Novel Combination Therapy of Cisplatin with a Molecular Promoter for Cancer Treatment. [Internet] [Thesis]. University of Waterloo; 2017. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/10012/11272.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhang Q. A Novel Combination Therapy of Cisplatin with a Molecular Promoter for Cancer Treatment. [Thesis]. University of Waterloo; 2017. Available from: http://hdl.handle.net/10012/11272
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
17.
Berinstein, Elliot.
The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.
Degree: 2016, University of Toronto
URL: http://hdl.handle.net/1807/90143
► The adoptive transfer of T lymphocytes expressing chimeric antigen receptors (CARs) has become a promising treatment for various cancers. CARs have been shown to redirect…
(more)
▼ The adoptive transfer of T lymphocytes expressing chimeric antigen receptors (CARs) has become a promising treatment for various cancers. CARs have been shown to redirect the cytotoxicity of T lymphocytes towards cancerous cells independent of the interactions between T cell receptors and major histocompatibility complexes. Given that CARs tie together an extracellular recognition domain with intracellular signaling domains of immune cells, there exists flexibility in designing CARs specific for different antigens in order to target different malignancies.
Here, we established murine antibodies specific for CD138 with the goal of designing a novel CAR. We designed a 2nd generation CAR using a single chain variable fragment derived from the 3E9B6 monoclonal antibody as the extracellular recognition domain. The expression of the 3E9B6 HL CAR specifically enhanced the cytotoxicity of the NK-92 cell line against CD138+ cells. Downstream activation of ZAP70 in NK-92 3E9B6 HL CAR cells was also dependent on the presence of CD138+ target cells. This work shows that the 3E9B6 HL CAR is functionally able to recognize CD138 and to initiate the CD3Îś activation pathway.
M.Sc.
2018-08-09 00:00:00
Advisors/Committee Members: Medin, Jeffrey A, Medical Biophysics.
Subjects/Keywords: Cancer; Gene Therapy; Immunotherapy; 0992
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APA (6th Edition):
Berinstein, E. (2016). The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/90143
Chicago Manual of Style (16th Edition):
Berinstein, Elliot. “The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.” 2016. Masters Thesis, University of Toronto. Accessed January 17, 2020.
http://hdl.handle.net/1807/90143.
MLA Handbook (7th Edition):
Berinstein, Elliot. “The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.” 2016. Web. 17 Jan 2020.
Vancouver:
Berinstein E. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. [Internet] [Masters thesis]. University of Toronto; 2016. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/1807/90143.
Council of Science Editors:
Berinstein E. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. [Masters Thesis]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/90143
University of New South Wales
18.
Armstrong, Luke.
Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic.
Degree: Biotechnology & Biomolecular Sciences, 2016, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/56172
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40188/SOURCE02?view=true
► Mesothelioma is a cancer of the pleural cavity in the lungs. The prognosis for people who develop this type of cancer is incredibly low, with…
(more)
▼ Mesothelioma is a
cancer of the pleural cavity in the lungs. The prognosis for people who develop this type of
cancer is incredibly low, with survival rates of less than 18 months for nearly all patients. Chemotherapy so far has not improved the quality of life significantly for mesothelioma patients. This means new methods of treating the disease are required.The EnGeneIC Dream Vector™ (EDV) is a 400nm bacterially derived nanocell which can be loaded with either chemotherapeutic drugs or genetic material and targeted with bispecific proteins to target
cancer cells directly and deliver the treatment specifically to these cells. For malignant pleural mesothelioma, a miR-16 mimic RNA molecule was loaded into the EDVs in order to prevent cell proliferation and promote apoptosis.In this study, several non-invasive methods were investigated to determine their value as markers pre and post EDV treatment in mesothelioma. First, circulating tumour cells (CTCs) were extracted from the whole blood samples of mesothelioma patients for diagnostic purposes based on their concentration. To corroborate this data, the biomarker mesothelin was also quantified from serum samples of these patients as well as in tissue culture experiments. Additionally, macrophages from tumour microenvironments in murine models of mesothelioma were isolated and identified based on their cell surface receptors. Methods for the identification of different classes of macrophage were developed to monitor their concentrations in the tumour microenvironment pre and post EDV treatment. This study found no significant results for the change in CTC concentrations of mesothelioma patients or the differentiation of macrophages. Surprisingly, a significant increase in mesothelin levels of cultured mesothelioma cells occurred when cell death was achieved. The trend in the patients matched this increase but was not significant.
Advisors/Committee Members: Marquis, Christopher, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, MacDiarmid, Jennifer, UNSW.
Subjects/Keywords: Cancer; Mesothelioma; EDV; Targeted therapy
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APA (6th Edition):
Armstrong, L. (2016). Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/56172 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40188/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Armstrong, Luke. “Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic.” 2016. Masters Thesis, University of New South Wales. Accessed January 17, 2020.
http://handle.unsw.edu.au/1959.4/56172 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40188/SOURCE02?view=true.
MLA Handbook (7th Edition):
Armstrong, Luke. “Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic.” 2016. Web. 17 Jan 2020.
Vancouver:
Armstrong L. Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic. [Internet] [Masters thesis]. University of New South Wales; 2016. [cited 2020 Jan 17].
Available from: http://handle.unsw.edu.au/1959.4/56172 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40188/SOURCE02?view=true.
Council of Science Editors:
Armstrong L. Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic. [Masters Thesis]. University of New South Wales; 2016. Available from: http://handle.unsw.edu.au/1959.4/56172 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40188/SOURCE02?view=true
University of Ottawa
19.
Watson, Margaret.
Characterizing a Novel Viral Sensitizer BI-D1870
.
Degree: 2019, University of Ottawa
URL: http://hdl.handle.net/10393/39364
► Oncolytic viruses (OVs) are an emerging cancer therapy that use an oncotropic virus to selectively infect and kill cancer cells, as well as stimulate long-lasting…
(more)
▼ Oncolytic viruses (OVs) are an emerging cancer therapy that use an oncotropic virus to selectively infect and kill cancer cells, as well as stimulate long-lasting anti-tumor immune responses. In order to achieve high therapeutic efficacy, OVs need sufficient replication within the tumor tissue to mediate these effects. However, OV’s infectivity varies between different tumors and the host’s immune system can rapidly clear the virus, hampering treatment efficiency. Oncolytic virus sensitizers are chemical compounds that specifically enhance OV’s infectivity and efficacy. In our lab, I found that treatment of various cancer cell lines with BI-D1870, a pan-RSK (ribosomal S6 kinase) inhibitor, resulted in augmented Herpes Simplex Virus-1 (HSV1) and Vesicular Stomatitis Virus (VSVΔ51) infectivity. I also demonstrated that the effects of BI-D1870 on viral infection are virus-specific, and that RSK inhibition is not the primary target causing the enhancement of HSV1 and VSVΔ51 infection. Finally, BI-D1870 structural analogs were generated in an attempt to enhance the efficacy and selectivity of BI-D1870-based OV sensitizers. One of the analogs synthesized, KA-019, showed an improvement in the augmentation of OV infection over BI-D1870. As a genetically engineered strain of HSV1 has been approved by FDA for treatment of melanoma, the results of my project propose a novel viral sensitizer to improve viral replication within tumour cells with the hope of improving therapeutic efficacy.
Subjects/Keywords: Oncolytic virus;
Cancer therapy
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APA (6th Edition):
Watson, M. (2019). Characterizing a Novel Viral Sensitizer BI-D1870
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/39364
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):
Watson, Margaret. “Characterizing a Novel Viral Sensitizer BI-D1870
.” 2019. Thesis, University of Ottawa. Accessed January 17, 2020.
http://hdl.handle.net/10393/39364.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Watson, Margaret. “Characterizing a Novel Viral Sensitizer BI-D1870
.” 2019. Web. 17 Jan 2020.
Vancouver:
Watson M. Characterizing a Novel Viral Sensitizer BI-D1870
. [Internet] [Thesis]. University of Ottawa; 2019. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/10393/39364.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Watson M. Characterizing a Novel Viral Sensitizer BI-D1870
. [Thesis]. University of Ottawa; 2019. Available from: http://hdl.handle.net/10393/39364
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Rutgers University
20.
Karjoo Diarkhan, Zahra, 1980-.
Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells.
Degree: PhD, Pharmaceutical Science, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/46367/
► Developing an efficient and safe system for gene delivery is considered the bottleneck of gene therapy, where a successful delivery of the nucleic acid can…
(more)
▼ Developing an efficient and safe system for gene delivery is considered the bottleneck of gene therapy, where a successful delivery of the nucleic acid can reverse a defective cellular pathway to normal, eradicate cancer at molecular level or simply make it more susceptible to current chemotherapies. Not only have the intracellular events played a crucial role for obtaining a successful gene delivery, but the interaction of nano-particles with extracellular factors should be studied as well. The goal of this study was to design, produce and optimize a non-viral gene delivery system for targeted delivery of nucleic acid such as reporter genes (e.g., green fluorescent protein) or therapeutic genes (e.g., suicide genes) to cancer cells. The system was designed in a way to be easily customized for different cancer types, still presenting a high level of targeted delivery. The first chapter of this thesis will focus on the concept of gene therapy and current systems used for this modality. Different types of vectors including viral and non-viral polymeric vectors will be discussed briefly and the advantages and disadvantages of each will be mentioned. We also discussed natured inspired biopolymers such as peptides and amino acid based vectors which are the fundamental premise of this study. In chapter II, the concept of suicide gene therapy will be explained. Additionally, the current enzyme/prodrug systems, different methods for delivery of suicide genes will be elaborated. In chapter III and IV, the new nanotechnology platform for targeted delivery of plasmid DNA to HER2-positive ovarian cancer cells and HER2-negative prostate cancer cells will be presented. In chapter III, the method for optimization of nanotechnology platform will be discussed and the features of optimized particles will be presented. Chapter IV explains the modification we introduced to the vectors’ primary structure to customize it for a different cell line. Also another method for optimization of amino-acid based vectors for in vivo delivery will be introduced. In these two chapters, the methods of designing and the efficiency of each vector to fulfill the expected goals as well as their safety will be discussed in details and supportive data will be presented.
Advisors/Committee Members: Hatefi, Arash (chair), Minko, Tamara (internal member), You, Guofeng (internal member), GOW, ANDREW (outside member).
Subjects/Keywords: Gene therapy; Cancer – Treatment; Nanoparticles
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APA (6th Edition):
Karjoo Diarkhan, Zahra, 1. (2015). Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/46367/
Chicago Manual of Style (16th Edition):
Karjoo Diarkhan, Zahra, 1980-. “Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells.” 2015. Doctoral Dissertation, Rutgers University. Accessed January 17, 2020.
https://rucore.libraries.rutgers.edu/rutgers-lib/46367/.
MLA Handbook (7th Edition):
Karjoo Diarkhan, Zahra, 1980-. “Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells.” 2015. Web. 17 Jan 2020.
Vancouver:
Karjoo Diarkhan, Zahra 1. Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2020 Jan 17].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/46367/.
Council of Science Editors:
Karjoo Diarkhan, Zahra 1. Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/46367/
Kansas State University
21.
Kunkel, Olivia Nicolle.
Effects of
acute and repeated heat therapy on prostate cancer cell survival
and viability.
Degree: MS, Department of
Kinesiology, 2019, Kansas State University
URL: http://hdl.handle.net/2097/40032
► Background: Despite advances in treatment options, prostate cancer remains the second-most diagnosed and second leading cause of cancer-related death in men in the United States.…
(more)
▼ Background: Despite advances in treatment options,
prostate
cancer remains the second-most diagnosed and second
leading cause of
cancer-related death in men in the United States.
The efficacy of conventional anti-
cancer treatments is dependent,
in part, on tumor blood flow and oxygenation. Tumor vasculature is
abnormal relative to healthy tissue, leading to reduced blood flow
and oxygen delivery, and thus, treatment resistance. An emerging
adjuvant to conventional treatment to overcome resistance to
radiation is heat
therapy. While heat
therapy may sensitize tumors
to radiation via increases in tumor blood flow and thus,
oxygenation, we hypothesized that heat-induced radiosensitization
occurs independent, in part, of tumor blood flow or oxygenation.
Methods: Clonogenic cell survival and cell viability were assessed
using human prostate
cancer (PC-3) cells in vitro. Individual
tissue culture flasks of PC-3 cells were randomized into 6 groups,
normothermic non-radiated (NT-NR, n=8), normothermic radiated
(NT-R, n=8), acute hyperthermic non-radiated (HTA-NR, n=8), acute
hyperthermic radiated (HTA-R, n=8), chronic (repeated) hyperthermic
non-radiated (HTC-NR, n=8), and chronic (repeated) hyperthermic
radiated (HTC-R, n=8) for both clonogenic cell survival and cell
viability assays. For assessment of both clonogenic cell survival
and cell viability, NT-NR and NT-R flasks were maintained in an
incubator at 37° C for the duration of the experiment. HTA-NR and
HTA-R flasks were maintained in an incubator at 37° C and heated in
a separate incubator to 41° C for 60 minutes prior to radiation.
HTC-NR and HTC-R flasks were maintained at 37º C and heated to 41º
C for 60 minutes every 48 hours for 3 heat treatments. Non-radiated
flasks were subjected to 0 Gy radiation, while radiated flasks were
subjected to 2 Gy radiation. For clonogenic cell survival, cells
were then plated in 60 mm tissue culture dishes at a density of 500
cells/plate and 1000 cells/plate in 5 replicates each per flask and
allowed to grow for 8 days in an incubator at 37° C. Cell survival
was assessed via counting the number of fixed and stained colonies
>50 cells at the completion of 8 days of incubation. For cell
viability, cells were plated into 96-well plates and incubated for
24, 48, and 72 hours before addition of MTT reagent for
quantification of absorbance. Data are presented as mean ± SEM.
Results: Clonogenic cell survival was significantly reduced between
NT-NR vs. NT-R, HTA-NR, HTA-R, and HTC-R (100 % ± 9.7% vs. 59.1 % ±
5.9 %, 72.4% ± 8.5%, 40.3% ± 3.1%, and 43.3% ± 3.4%, respectively;
p < 0.05). There were no differences between NT-R and HTA-NR or
HTC-NR. Conclusions: This investigation indicates that 60 minutes
of mild-temperature hyperthermia before radiation treatment does
not enhance the efficacy of radiation treatment, but that heat
therapy alone may be as effective as low-dose radiation in vitro.
Further, given that 2 Gy radiation alone (representative of one
radiation fraction given clinically) was not more effective at
reducing
cancer cell…
Advisors/Committee Members: Brad J. Behnke.
Subjects/Keywords: Prostate
cancer;
Radiosensitivity; Heat
therapy
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APA ·
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Export
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Manager
APA (6th Edition):
Kunkel, O. N. (2019). Effects of
acute and repeated heat therapy on prostate cancer cell survival
and viability. (Masters Thesis). Kansas State University. Retrieved from http://hdl.handle.net/2097/40032
Chicago Manual of Style (16th Edition):
Kunkel, Olivia Nicolle. “Effects of
acute and repeated heat therapy on prostate cancer cell survival
and viability.” 2019. Masters Thesis, Kansas State University. Accessed January 17, 2020.
http://hdl.handle.net/2097/40032.
MLA Handbook (7th Edition):
Kunkel, Olivia Nicolle. “Effects of
acute and repeated heat therapy on prostate cancer cell survival
and viability.” 2019. Web. 17 Jan 2020.
Vancouver:
Kunkel ON. Effects of
acute and repeated heat therapy on prostate cancer cell survival
and viability. [Internet] [Masters thesis]. Kansas State University; 2019. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/2097/40032.
Council of Science Editors:
Kunkel ON. Effects of
acute and repeated heat therapy on prostate cancer cell survival
and viability. [Masters Thesis]. Kansas State University; 2019. Available from: http://hdl.handle.net/2097/40032
University of Gothenburg / Göteborgs Universitet
22.
Nordenskjöld, Anna.
To predict results of breast cancer therapy.
Degree: 2019, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/58241
► We have used the almost complete national Swedish Cancer register, regional quality management register and one randomized adjuvant endocrine trial to study, the effect of…
(more)
▼ We have used the almost complete national Swedish Cancer register, regional quality management register and one randomized adjuvant endocrine trial to study, the effect of radiotherapy in breast cancer with 1-3 positive nodes (study 1), the effect of tamoxifen in estrogen receptor (ER)-positive tumors depending on expression of the progesterone receptor (PR) (studies 2 and 4) and the development of the survival rates of breast cancer in Sweden 1989-2013 (study 3)
Study 1. We compared relative breast cancer survival in two Swedish health care regions that between 1989 and 2006 had different guidelines for postoperative radiotherapy. Patients with 1–3 positive lymph nodes in the western region received radiotherapy of the remaining parts of the breast only, while patients in the south eastern region also received therapy of regional lymph nodes. Other aspects of the guidelines were very similar including those for screening mammography, surgery and adjuvant medical treatment. Results: The 10-year relative survival for patients with 1–3 positive lymph nodes was 78% in the western region and 77% in the southeastern region (p=0.12). Conclusions: There was little or no influence of addition of lymph node radiotherapy on survival in patients with 1–3 positive lymph nodes in a population with screening mammography and modern systemic treatment.
Studies 2 and 4 We investigated the independent predictive value of progesterone receptor (PR) determined with immunohistochemistry (IHC) in estrogen receptor (ER) positive tumors from patients participating in the Stockholm trial of adjuvant tamoxifen. Methods We evaluated patients without lymph node metastasis for whom PR in study 2 was determined by IHC in tissue micro arrays (thin cores of tumor tissue). In study 4, PR was scored by gene expression and by IHC of entire tumor sections and separate analyses of patients with luminal A tumors were performed. Conclusions PR positivity determined by IHC or gene expression is a marker indicating long-term benefit from adjuvant tamoxifen. We observed a very marked benefit for patients with PR positive luminal A tumors.
Study 3 During the recent decades, breast cancer survival has gradually improved but there is limited knowledge on the improvement in population-based studies of patients diagnosed with different stages of disease and in different age groups. Patients and methods. In two Swedish health care regions a total of 42 220 female breast cancer patients below 90 years of age were diagnosed between 1989 and 2013. Results. Using patients diagnosed 1989-1993 as a reference the relative risk of 5 year mortality decreased with 49% (ci95% 45 – 58) for patients diagnosed in the end of the observation period. Conclusions. Improvements were seen in all age groups but was unevenly distributed between stages and age groups pointing to the need for…
Subjects/Keywords: breast cancer; endocrine therapy; survival
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APA (6th Edition):
Nordenskjöld, A. (2019). To predict results of breast cancer therapy. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/58241
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):
Nordenskjöld, Anna. “To predict results of breast cancer therapy.” 2019. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed January 17, 2020.
http://hdl.handle.net/2077/58241.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nordenskjöld, Anna. “To predict results of breast cancer therapy.” 2019. Web. 17 Jan 2020.
Vancouver:
Nordenskjöld A. To predict results of breast cancer therapy. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2019. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/2077/58241.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nordenskjöld A. To predict results of breast cancer therapy. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2019. Available from: http://hdl.handle.net/2077/58241
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Georgia State University
23.
Yang, Lingyun.
Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions.
Degree: MS, Chemistry, 2017, Georgia State University
URL: https://scholarworks.gsu.edu/chemistry_theses/104
► Hypoxia Inducible Factors (HIFs) are very important transcription factors that can respond to low oxygen concentrations in the cellular environment. Inhibition of HIF’s transcriptional…
(more)
▼ Hypoxia Inducible Factors (HIFs) are very important transcription factors that can respond to low oxygen concentrations in the cellular environment. Inhibition of HIF’s transcriptional activity represents a promising approach to new anticancer compounds. Herein, we describe the design and synthesis of a series of HIF-1 inhibitors. Evaluation of these inhibitors using a cell-based luciferase assay led to the discovery compounds with sub-micromolar potency.
Advisors/Committee Members: Dr. Binghe Wang, Dr. Donald Hamelberg, Dr. Suri S. Iyer.
Subjects/Keywords: hypoxia; hif-1; cancer therapy
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APA (6th Edition):
Yang, L. (2017). Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions. (Thesis). Georgia State University. Retrieved from https://scholarworks.gsu.edu/chemistry_theses/104
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):
Yang, Lingyun. “Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions.” 2017. Thesis, Georgia State University. Accessed January 17, 2020.
https://scholarworks.gsu.edu/chemistry_theses/104.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yang, Lingyun. “Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions.” 2017. Web. 17 Jan 2020.
Vancouver:
Yang L. Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions. [Internet] [Thesis]. Georgia State University; 2017. [cited 2020 Jan 17].
Available from: https://scholarworks.gsu.edu/chemistry_theses/104.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yang L. Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions. [Thesis]. Georgia State University; 2017. Available from: https://scholarworks.gsu.edu/chemistry_theses/104
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Melbourne
24.
Au-Yeung, George.
Cyclin E1 as a therapeutic target in high grade serous ovarian cancer.
Degree: 2017, University of Melbourne
URL: http://hdl.handle.net/11343/191772
► The central theme of this thesis is developing therapeutic strategies to selectively target CCNE1 amplified high grade serous ovarian cancer (HGSC). Patients with CCNE1 amplified…
(more)
▼ The central theme of this thesis is developing therapeutic strategies to selectively target CCNE1 amplified high grade serous ovarian cancer (HGSC). Patients with CCNE1 amplified HGSC represent a key unmet clinical need given that they are associated with primary treatment resistance and poor clinical outcome. Novel therapeutic strategies are urgently required in order to provide these patients with additional treatment options.
Using short interfering RNA and short hairpin RNA, I demonstrated selective sensitivity of CCNE1 amplified HGSC to CDK2 gene suppression. However, I did not demonstrate similar amplicon dependent sensitivity to dinaciclib, a potent small molecule inhibitor of multiple CDKs. In order to identify drug combinations that would synergise with dinaciclib, I performed a high throughput compound screen in CCNE1 amplified HGSC cell lines. I identified a combination of dinaciclib and MK-2206, an AKT inhibitor, that was selectively synergistic in in vitro and in vivo models of CCNE1 amplified HGSC. CCNE1 and AKT2 were noted to be co-amplified in primary HGSC samples, and a number of genes in the AKT pathway were found to be required in CCNE1 amplified HGSC cell lines. Furthermore, over-expression of cyclin E1 and AKT isoforms resulted in uncontrolled growth characteristics in TP53-mutant fallopian tube secretory cells, the proposed cell of origin for HGSC. Taken together, these findings suggest that co-operative interaction between CCNE1 and the AKT pathway in HGSC may be exploited therapeutically.
I also explored the potential mechanisms of resistance to CDK inhibitors by generating cell lines resistant to dinaciclib. Dinaciclib in combination with multiple BH3-mimetic compounds was noted to be synergistic in CDK-inhibitor resistant cell lines. Upregulation of multiple anti-apoptotic genes was observed in resistant cell lines compared to parental sensitive cell lines, suggesting that this is a potential mechanism of resistance to CDK inhibitors.
Targeting homologous recombination (HR) may also be a therapeutic option in CCNE1 amplified HGSC. Proteasome inhibitors such as bortezomib have been shown to be indirect inhibitors of HR, and I showed that CCNE1 amplified cell lines were highly sensitive to bortezomib and MLN9708, a second generation proteasome inhibitor. Potential synergistic combinations with bortezomib were identified in a high throughput compound screen, including a number of HDAC inhibitors, suggesting a possible class effect.
Subjects/Keywords: Ovarian cancer; Molecular targets; Cancer therapy
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APA (6th Edition):
Au-Yeung, G. (2017). Cyclin E1 as a therapeutic target in high grade serous ovarian cancer. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/191772
Chicago Manual of Style (16th Edition):
Au-Yeung, George. “Cyclin E1 as a therapeutic target in high grade serous ovarian cancer.” 2017. Doctoral Dissertation, University of Melbourne. Accessed January 17, 2020.
http://hdl.handle.net/11343/191772.
MLA Handbook (7th Edition):
Au-Yeung, George. “Cyclin E1 as a therapeutic target in high grade serous ovarian cancer.” 2017. Web. 17 Jan 2020.
Vancouver:
Au-Yeung G. Cyclin E1 as a therapeutic target in high grade serous ovarian cancer. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/11343/191772.
Council of Science Editors:
Au-Yeung G. Cyclin E1 as a therapeutic target in high grade serous ovarian cancer. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/191772
Rutgers University
25.
Salman Noori, Faranak, 1986-.
Stem cell-based ovarian cancer suicide gene therapy.
Degree: PhD, Pharmaceutical Science, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48643/
► Cancer is a leading cause of death worldwide, resulting in 8.2 million deaths in 2012. Tumor suicide gene therapy is among the novel targeted therapeutics…
(more)
▼ Cancer is a leading cause of death worldwide, resulting in 8.2 million deaths in 2012. Tumor suicide gene therapy is among the novel targeted therapeutics that has demonstrated promising results. There are two important factors that specify the efficiency and safety of the suicide gene therapy systems. One is vector safety and efficiency and the other enzyme/prodrug anticancer efficacy. Among the vectors employed for delivery of therapeutics, mesenchymal stem cells (MSCs) have attracted tremendous amount of attention due to their unique features such as inherent tumor tropism and low immunogenicity. The objective of this research was to take advantage of MSCs as cell-based vectors to develop an efficient and safe suicide gene therapy system for cancer. As a first step towards achieving the objective, I engineered a panel of MSCs that were genetically modified to express five different suicide genes and compared their anti-tumor efficiency in vitro and in vivo. Among the enzyme/prodrug systems tested, genetically modified MSCs that expressed yeast cytosine deaminase enzyme (yCD-UPRT) in combination with prodrug 5-fluorocytosine (5FC) demonstrated the highest anti-tumor efficacy. In the next step we focused on developing a safe and efficient method for stem cell engineering. Since current commercially available transfection agents are inefficient and toxic to MSCs, I made an attempt to develop a safe and efficient gene delivery system suitable for MSC engineering. Using a previously developed vector in Dr. Hatefi’s lab as a template, I recombinantly engineered a new vector for MSC transfection. This vector is comprised of a cell penetrating peptide for penetration into MSCs, four histone H2A repeats to condense plasmid DNA (pDNA) into nanosize particles and a fusogenic peptide named GALA to facilitate endosomal escape. The results of this study illustrated that the newly developed recombinant vector could efficiently and safely transfect MSCs. In conclusion we not only successfully developed a safe and efficient method for stem cell engineering but also identified an enzyme/prodrug system that could be used for effective treatment of ovarian cancer.
Advisors/Committee Members: Minko, Tamara (chair).
Subjects/Keywords: Cancer – Gene therapy; Ovaries – Cancer; Stem cells
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APA (6th Edition):
Salman Noori, Faranak, 1. (2015). Stem cell-based ovarian cancer suicide gene therapy. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48643/
Chicago Manual of Style (16th Edition):
Salman Noori, Faranak, 1986-. “Stem cell-based ovarian cancer suicide gene therapy.” 2015. Doctoral Dissertation, Rutgers University. Accessed January 17, 2020.
https://rucore.libraries.rutgers.edu/rutgers-lib/48643/.
MLA Handbook (7th Edition):
Salman Noori, Faranak, 1986-. “Stem cell-based ovarian cancer suicide gene therapy.” 2015. Web. 17 Jan 2020.
Vancouver:
Salman Noori, Faranak 1. Stem cell-based ovarian cancer suicide gene therapy. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2020 Jan 17].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48643/.
Council of Science Editors:
Salman Noori, Faranak 1. Stem cell-based ovarian cancer suicide gene therapy. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48643/
University of Western Australia
26.
Brown, Matthew David.
An empirical framework for combining surgery with immune therapy.
Degree: PhD, 2007, University of Western Australia
URL: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=30337&local_base=GEN01-INS01
► [Truncated abstract] Only 50% of patients diagnosed with cancer can expect to survive more than five years,1 and overall cure rates have remained static for…
(more)
▼ [Truncated abstract] Only 50% of patients diagnosed with cancer can expect to survive more than five years,1 and overall cure rates have remained static for some thirty years.2,3 Within the last decade, there has been resurgence in interest for the use of immune therapy to improve oncologocial outcomes. While immune treatments have been disappointing as monotherapies (responses are usually <20%),4-9 there is emerging evidence that immune therapy can be effective when combined with surgery.10-19 Although there is clear evidence that surgery impacts on general aspects of immunity, little is known about how surgery affects key parameters of tumour-specific immunity. Until such insights are obtained, the optimum strategy for combining surgery and immune therapy is likely to remain unclear. In this thesis, a haemagglutinin (HA) transfected murine mesothelioma tumour (AB1HA)20 was employed to study the effects of surgery (primary resection and/or sentinel node biopsy) on tumour-specific immunity. Using this tumour model, the HA-specific immune response was tracked in vivo, to “spy” upon endogenous tumour-specific immunity. Particular parameters of focus were: tumour antigen cross presentation, tumour-specific cytotoxic T lymphocytes (CTL), sentinel nodes, and resistance to re-challenge. Antigen presentation was found to be highly efficient since both micro-metastases and small primary tumours were associated with robust antigen presentation. Antigen presentation was directly related to tumour size, but always confined to the sentinel lymph nodes. Surgery, in the forms of primary resection and/or sentinel node biopsy, had a profound effect on antigen presentation. Primary tumour resection produced a gradual decline in antigen presentation, until it was no longer detectable at two weeks after surgery. As was the case pre-operatively, tumour antigen presentation was confined to the sentinel nodes for all post-operative time points.
When sentinel node biopsy was combined with primary resection, antigen presentation could be immediately and completely ablated. If tumour remained in situ when sentinel nodes were removed, antigen presentation shifted to more distant (or systemic) sites. It was not possible to predict the nodes which presented tumour antigen after sentinel node biopsy, but a lag phase of three to five days preceded the shift. This thesis highlights the complex role of tumour antigen in the adaptive immune response. While surgery could reduce tumour antigen, this reduction correlated with an improvement in CTL function and tumour resistance. Not only did CTL function improve, but unlike pre-operatively, it was detectable systemically after surgery. It was postulated that tumour antigen presentation had a suppressive effect on tumour-specific immunity, and may tether tumour-specific CD8+ to the sentinel node. By extension, surgery could “slip the antigen tether”, releasing CD8+ from the sentinel nodes and improving systemic CD8+-mediated tumour resistance. The contribution of sentinel nodes was similarly complex.…
Subjects/Keywords: Cancer; Cancer; Cancer; Cancer; Cancer; Surgery; Tumor antigens; Tumors; Tumour immunology; Surgery; Immune therapy
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APA ·
Chicago ·
MLA ·
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CSE |
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APA (6th Edition):
Brown, M. D. (2007). An empirical framework for combining surgery with immune therapy. (Doctoral Dissertation). University of Western Australia. Retrieved from http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=30337&local_base=GEN01-INS01
Chicago Manual of Style (16th Edition):
Brown, Matthew David. “An empirical framework for combining surgery with immune therapy.” 2007. Doctoral Dissertation, University of Western Australia. Accessed January 17, 2020.
http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=30337&local_base=GEN01-INS01.
MLA Handbook (7th Edition):
Brown, Matthew David. “An empirical framework for combining surgery with immune therapy.” 2007. Web. 17 Jan 2020.
Vancouver:
Brown MD. An empirical framework for combining surgery with immune therapy. [Internet] [Doctoral dissertation]. University of Western Australia; 2007. [cited 2020 Jan 17].
Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=30337&local_base=GEN01-INS01.
Council of Science Editors:
Brown MD. An empirical framework for combining surgery with immune therapy. [Doctoral Dissertation]. University of Western Australia; 2007. Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=30337&local_base=GEN01-INS01
University College Cork
27.
Sadadcharam, Mira.
Expanding the use of electroporation from cutaneous to intraluminal and systemic applications.
Degree: 2015, University College Cork
URL: http://hdl.handle.net/10468/3484
► Cancer is a global phenomenon transcending the boundaries of age, race, geography and socioeconomic background. As our understanding of cancer cell biology has improved, we…
(more)
▼ Cancer is a global phenomenon transcending the boundaries of age, race, geography and socioeconomic background. As our understanding of
cancer cell biology has improved, we have developed a growing appreciation of
cancer as a systemic disease. However, our improved understanding has been matched by
cancer cell evolution and it is becoming increasingly clear that the future of anti-
cancer therapies lies in a multi-modal approach. In this thesis, we adopted a “three-legged stool” approach to anti-
cancer therapy. The first leg encompasses primary tumour ablation. We developed the EndoVe device, enabling endoscopic electroporation of gastrointestinal tissues and tumours. We conducted a pre-clinical evaluation of the EndoVe prior to a phase I/II clinical study and validated the efficacy of the system in the treatment of cutaneous murine gastrointestinal tumours. In addition, we established the safety and utility of endoscopically-delivered electroporation through evaluation in a porcine model and by treating canine colorectal tumours. The second leg of our stool involved immunotherapy. We opted for a combination regime of Treg depletion and immunotherapy with the cytokine, pGMCSF-B7.1. While we observed a modest but significant improvement of primary tumour burden, the combination regime had the remarkable effect of eradicating pre-existing, established lung metastases when compared to the use of either treatment alone. The potential clinical implications of this should not be understated as nine out of ten
cancer deaths are directly attributable to metastatic disease burden. The third and final leg of our anti-
cancer strategy involved the development of a DNA-based enhanced expression vector (pEEV), with improved expression capabilities across a range of tissue histologies over standard non-viral DNA vectors. Following on from this observation, we then utilised this pEEV vector system in combination with the immune cytokine GMCSF-B7.1 leading to robust recruitment of immune effector cells with consequent potent, durable and transferable tumour antigen-specific responses.
Advisors/Committee Members: Soden, Declan, Forde, Patrick.
Subjects/Keywords: Electroporation; Electrochemotherapy; EndoVe; Cancer immunogene therapy; Immune therapy; Gene therapy
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APA ·
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MLA ·
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CSE |
Export
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APA (6th Edition):
Sadadcharam, M. (2015). Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. (Thesis). University College Cork. Retrieved from http://hdl.handle.net/10468/3484
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):
Sadadcharam, Mira. “Expanding the use of electroporation from cutaneous to intraluminal and systemic applications.” 2015. Thesis, University College Cork. Accessed January 17, 2020.
http://hdl.handle.net/10468/3484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sadadcharam, Mira. “Expanding the use of electroporation from cutaneous to intraluminal and systemic applications.” 2015. Web. 17 Jan 2020.
Vancouver:
Sadadcharam M. Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. [Internet] [Thesis]. University College Cork; 2015. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/10468/3484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sadadcharam M. Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. [Thesis]. University College Cork; 2015. Available from: http://hdl.handle.net/10468/3484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Waterloo
28.
Zargar, Bahram.
A Synthetic Biology Approach to Bacteria Mediated Tumor Targeting.
Degree: 2014, University of Waterloo
URL: http://hdl.handle.net/10012/9014
► Development of a drug delivery agent that selectively targets and destroys tumor cells with minimal toxicity to normal tissues is a major challenge in cancer…
(more)
▼ Development of a drug delivery agent that selectively targets and destroys tumor cells with minimal toxicity to normal tissues is a major challenge in cancer therapy. It has been known for more than 60 years that anaerobic bacteria such as Clostridium can selectively colonize inside the necrotic core of solid tumors. Inoculation of a tumor by wild type Clostridium results in colonization of the necrotic core and consequently significant tumor destruction. This treatment strategy is hampered by the fact that the outer rim of the tumor is typically viable, and so does not present an anaerobic environment. As a result, colonization by Clostridium is unlikely to lead to complete tumor regression, since tumor regrowth occurs from the remaining outer viable rim, as evidenced by clinical trials. This project aims to address the problem of regrowth by developing a novel selectively aerotolerant strain of Clostridium that cannot colonize inside healthy tissue, but that could grow in the viable rim of an infected tumor. We have engineered a gene coding for an aerotolerance enzyme into Clostridium sporogenes. To couple the selective expression of this gene to tumor colonization, it can be placed under the control of a promoter activated by a synthetic quorum sensing circuit. This document describes the foundational work that will allow this system to be implemented. A suitable strain of C. sporogenes was selected, and a cloning technique (via conjugation with E. coli) was implemented. Expression of the aerotolerance enzyme and a synthetic quorum sensing circuit were verified in engineered colonies, and appropriate function was confirmed in both cases. Additionally, a model-based design exercise was carried out in order to better understand the system behavior and to identify key parameters for controlling the bacterial population. This analysis was based on mathematical models of the quorum-sensing circuit and of bacterial growth in the tumor environment. Sensitivity analysis reveals the design parameters that have the most significant impact on the extent and specificity of colonization of the viable rim, and thus provides insights into efficient design of the synthetic mechanism.
Subjects/Keywords: Synthetic Biology; Bacteria Mediated Cancer Therapy; Cancer; Clostridium Mediated Cancer Therapy; Quorum Sensing; S. aureus
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APA ·
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Export
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APA (6th Edition):
Zargar, B. (2014). A Synthetic Biology Approach to Bacteria Mediated Tumor Targeting. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/9014
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):
Zargar, Bahram. “A Synthetic Biology Approach to Bacteria Mediated Tumor Targeting.” 2014. Thesis, University of Waterloo. Accessed January 17, 2020.
http://hdl.handle.net/10012/9014.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zargar, Bahram. “A Synthetic Biology Approach to Bacteria Mediated Tumor Targeting.” 2014. Web. 17 Jan 2020.
Vancouver:
Zargar B. A Synthetic Biology Approach to Bacteria Mediated Tumor Targeting. [Internet] [Thesis]. University of Waterloo; 2014. [cited 2020 Jan 17].
Available from: http://hdl.handle.net/10012/9014.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zargar B. A Synthetic Biology Approach to Bacteria Mediated Tumor Targeting. [Thesis]. University of Waterloo; 2014. Available from: http://hdl.handle.net/10012/9014
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
East Carolina University
29.
Piland, Meagan Nicole.
Effectiveness of a Cancer Center Based Physical Activity
Counseling Intervention in Breast Cancer Survivors.
Degree: 2011, East Carolina University
URL: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=14034
► The purpose of this study was to examine the effectiveness of a cancer center-based physical activity counseling program compared to an attention control condition for…
(more)
▼ The purpose of this study was to examine the
effectiveness of a
cancer center-based physical activity counseling
program compared to an attention control condition for (a)
improving quality of life and (b) increasing physical activity
levels in a rural population of breast
cancer survivors. Twenty
post-treatment breast
cancer survivors were recruited through
primarily post-treatment follow-up clinics as well as through a
fitness center or university listserv and were randomized to a
cancer center based physical activity counseling program (CCB)
condition or an attention control (AC) condition. Participants
randomized to the CCB condition received a 20-30 minutes
face-to-face physical activity counseling session using
Motivational Interviewing with a trained fitness consultant at the
site of recruitment. The intervention lasted four weeks and
included weekly telephone calls aimed at providing motivation and
exploring topics such as goal setting and overcoming barriers to
physical activity. AC condition participants were also telephoned
weekly to match the attention that the participants of the CCB
group received. Participants in both conditions received a
pedometer weekly step logs and a package of print materials
tailored for breast
cancer survivors outlining many physical
activity topics (e.g. benefits and barriers of exercise setting
goals support from others and planning an exercise program).
Participants in both conditions were instructed to record their
steps every day for four weeks and again during the eighth week
after the start of the intervention during the follow-up phase.
Physical activity was assessed by pedometer steps and the
International Physical Activity Questionnaire (IPAQ). Quality of
life was assessed using the Functional Assessment of
Cancer
Therapy-Breast (FACT-B). Both the IPAQ and FACT-B questionnaires
were administered at the time of recruitment immediately at the end
of the four week intervention and after the follow-up phase.
Significant improvements in self-reported moderate and
moderate-to-vigorous physical activity were noted in both
conditions across the course of the intervention while no
significant improvements were seen in quality of life scores.
Participants in the CCB condition had significant improvements in
change scores in pedometer steps from pre-intervention to follow-up
as compared with the AC condition. Based on these findings the CCB
condition was successful in increasing objectively measured
physical activity in post-treatment breast
cancer survivors
compared to the AC condition however it did not improve quality of
life. Future efforts should include a larger sample size that
better represents the general population of breast
cancer survivors
and a longer intervention to better determine the effectiveness of
this particular intervention. ; Kinesiology, Counseling
psychology, Animal behavior
Advisors/Committee Members: Kristina H. Karvinen (advisor).
Subjects/Keywords: Breast – Cancer; Cancer – Patients – Rehabilitation; Cancer – Physical therapy
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APA ·
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MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Piland, M. N. (2011). Effectiveness of a Cancer Center Based Physical Activity
Counseling Intervention in Breast Cancer Survivors. (Masters Thesis). East Carolina University. Retrieved from http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=14034
Chicago Manual of Style (16th Edition):
Piland, Meagan Nicole. “Effectiveness of a Cancer Center Based Physical Activity
Counseling Intervention in Breast Cancer Survivors.” 2011. Masters Thesis, East Carolina University. Accessed January 17, 2020.
http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=14034.
MLA Handbook (7th Edition):
Piland, Meagan Nicole. “Effectiveness of a Cancer Center Based Physical Activity
Counseling Intervention in Breast Cancer Survivors.” 2011. Web. 17 Jan 2020.
Vancouver:
Piland MN. Effectiveness of a Cancer Center Based Physical Activity
Counseling Intervention in Breast Cancer Survivors. [Internet] [Masters thesis]. East Carolina University; 2011. [cited 2020 Jan 17].
Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=14034.
Council of Science Editors:
Piland MN. Effectiveness of a Cancer Center Based Physical Activity
Counseling Intervention in Breast Cancer Survivors. [Masters Thesis]. East Carolina University; 2011. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=14034
University of Alberta
30.
Miklavcic, John.
Ganglioside Increases Metastatic Potential and
Susceptibility of Prostate Cancer to Gene Therapy in vitro.
Degree: MS, Department of Agricultural, Food and Nutritional
Science, 2009, University of Alberta
URL: https://era.library.ualberta.ca/files/m613mx76k
► Prostate cancer (CaP) is the 2nd most common cancer in North American men. Tumour management strategies are appropriate for early stage disease, but advanced disease…
(more)
▼ Prostate cancer (CaP) is the 2nd most common cancer in
North American men. Tumour management strategies are appropriate
for early stage disease, but advanced disease has a poor prognosis
and requires prompt treatment. Therefore, research into delay of
tumour progression and efficacious treatment of aggressive cancer
are of interest. Ganglioside was assessed for its role in altering
markers of metastatic potential and susceptibility of CaP to
adenovirus-mediated gene therapy. Healthy (RWPE-1) and malignant
(DU-145, PC-3) prostate cells were cultured with or without mixed
ganglioside. Differences in growth, ganglioside and integrin
densities, and adenoviral infectivity were assessed between
treatment and control groups. Ganglioside decreased (p<0.01)
growth of PC-3 cells relative to untreated control. Ganglioside
decreased (p<0.01) GD1a and increased (p<0.04)
integrin densities in malignant prostate cells, suggesting
ganglioside may increase metastatic potential of CaP. Ganglioside
significantly increased adenovirus entry in PC-3 cells, thereby
improving susceptibility of CaP to adenovirus-mediated gene
therapy.
Subjects/Keywords: adenovirus; gene therapy; metastasis; prostate cancer; ganglioside
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APA ·
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Miklavcic, J. (2009). Ganglioside Increases Metastatic Potential and
Susceptibility of Prostate Cancer to Gene Therapy in vitro. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/m613mx76k
Chicago Manual of Style (16th Edition):
Miklavcic, John. “Ganglioside Increases Metastatic Potential and
Susceptibility of Prostate Cancer to Gene Therapy in vitro.” 2009. Masters Thesis, University of Alberta. Accessed January 17, 2020.
https://era.library.ualberta.ca/files/m613mx76k.
MLA Handbook (7th Edition):
Miklavcic, John. “Ganglioside Increases Metastatic Potential and
Susceptibility of Prostate Cancer to Gene Therapy in vitro.” 2009. Web. 17 Jan 2020.
Vancouver:
Miklavcic J. Ganglioside Increases Metastatic Potential and
Susceptibility of Prostate Cancer to Gene Therapy in vitro. [Internet] [Masters thesis]. University of Alberta; 2009. [cited 2020 Jan 17].
Available from: https://era.library.ualberta.ca/files/m613mx76k.
Council of Science Editors:
Miklavcic J. Ganglioside Increases Metastatic Potential and
Susceptibility of Prostate Cancer to Gene Therapy in vitro. [Masters Thesis]. University of Alberta; 2009. Available from: https://era.library.ualberta.ca/files/m613mx76k
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Open Access Theses and Dissertations