You searched for subject:(Drug resistance)
.
Showing records 1 – 30 of
1300 total matches.
◁ [1] [2] [3] [4] [5] … [44] ▶
1.
Wong, Neelum.
Development of Improved Chemotherapeutics in Pancreatic and
Colorectal Cancer: Ceramide as a Potential Adjuvant with Sigma-2
Receptor Ligands.
Degree: Department of Molecular Pharmacology, Physiology and
Biotechnology, 2018, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:792844/
► Pancreatic and colorectal cancer are highly aggressive and challenging to treat. Both cancers have low survival rates and there is a need for more elaborate…
(more)
▼ Pancreatic and colorectal cancer are highly aggressive
and challenging to treat. Both cancers have low survival rates and
there is a need for more elaborate therapies as patients suffer
from
drug resistance to commonly used chemotherapeutics. The
difficulty in finding novel and effective treatments has led
researchers to explore the sigma-2 receptor and the sphingolipid
ceramide for their roles in inducing apoptosis in cancer cells.
Ceramide has recently been studied for its ability to potentiate
chemotherapeutics for pancreatic and colorectal cancer patients
with a mutation in the KRAS oncogene that contributes to
drug
resistance. The sigma-2 receptor is upregulated in cancer cells and
a cytotoxic response by the activation of the receptor in cancer
cells is a property that can be exploited in the attempt to
overcome
drug resistance and kill pancreatic and colorectal cancer
cells. Here, the cytotoxicity of C-6 ceramide on cell viability for
PANC-1, MIA PaCA-2, and L3.6 pancreatic cancer cell lines and
KRAS-wild-type SW48 and KRAS-mutated SW480 colorectal cell lines
was found using the MTT cell viability assay. Additionally, this
study revealed that a combination treatment of C-6 ceramide with
the sigma-2 receptor agonists, siramesine and SV119 had a
synergistic effect on cytotoxicity while C-6 ceramide with the
sigma-2 receptor agonist, MAM03055A had an additive effect on the
colorectal cancer cell lines. Interestingly, no difference in
cytotoxicity was observed in the combination therapy treatments
between the KRAS-wild-type and KRAS-mutated cell lines. Altogether,
this data suggests that a combination treatment of ceramide with
sigma-2 receptor agonists is promising for the development of
improved chemotherapeutics for pancreatic and colorectal
cancer.
Advisors/Committee Members: Mathiowitz, Edith (Reader), Morgan, Jeffrey (Reader), Bowen, Wayne (Advisor).
Subjects/Keywords: Drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wong, N. (2018). Development of Improved Chemotherapeutics in Pancreatic and
Colorectal Cancer: Ceramide as a Potential Adjuvant with Sigma-2
Receptor Ligands. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792844/
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):
Wong, Neelum. “Development of Improved Chemotherapeutics in Pancreatic and
Colorectal Cancer: Ceramide as a Potential Adjuvant with Sigma-2
Receptor Ligands.” 2018. Thesis, Brown University. Accessed March 04, 2021.
https://repository.library.brown.edu/studio/item/bdr:792844/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wong, Neelum. “Development of Improved Chemotherapeutics in Pancreatic and
Colorectal Cancer: Ceramide as a Potential Adjuvant with Sigma-2
Receptor Ligands.” 2018. Web. 04 Mar 2021.
Vancouver:
Wong N. Development of Improved Chemotherapeutics in Pancreatic and
Colorectal Cancer: Ceramide as a Potential Adjuvant with Sigma-2
Receptor Ligands. [Internet] [Thesis]. Brown University; 2018. [cited 2021 Mar 04].
Available from: https://repository.library.brown.edu/studio/item/bdr:792844/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wong N. Development of Improved Chemotherapeutics in Pancreatic and
Colorectal Cancer: Ceramide as a Potential Adjuvant with Sigma-2
Receptor Ligands. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792844/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Shawa, Misheck.
Risk factors and Alleles of extended spectrum Beta-Lactamase(ESBL) producing Escherichia coli at the University Teaching Hospital, Zambia.
Degree: 2015, University of Zimbabwe
URL: http://dspace.unza.zm/handle/123456789/4464
► The limitation of antibacterial treatment options imposed by the emergence of bacterial resistant organisms calls for the correct identification of the genes involved in mediating…
(more)
▼ The limitation of antibacterial treatment options imposed by the emergence of bacterial resistant organisms calls for the correct identification of the genes involved in mediating resistance. In this study, antimicrobial resistance was determined in terms of the presence of extended-spectrum beta-lactamases (ESBL) among Escherichia coli isolates obtained from patients admitted at the University Teaching Hospital (UTH) in Zambia. A total of 400 rectal swabs were obtained and subjected to initial screening using MacConkey agar supplemented with cefotaxime. blaTEM, blaSHV and bla CTX-M genes in ESBL producing E. coli were detected using Polymerase Chain Reaction (PCR). All CTX-M positive isolates were subjected to sensitivity patterns using 11 different antibiotics: ampicillin (AMP), trimethoprim-sulphamethoxazole (SXT), streptomycin (STR), tetracycline (TET), gentamycin (GEN), nalidixic acid (NAL), ceftazidime (CAZ), chloramphenicol (CHL), norfloxacin (NOR), ciprofloxacin (CIP) and cefotaxime (CTX).
The prevalence of ESBL producing E. coli was 19% (76/400). Among the ESBL producing E. coli, 25 out of 76 (32.9%) were positive for CTX-M genes. Of the 25 CTX-M positive isolates, 9 (36%) isolates were positive for SHV genes and 9 (36%) were positive for TEM genes. The highest resistance was found to be to nalidixic acid (96%), followed by sulfamethoxazole-trimethoprim, tetracycline and ceftazidime (92% each). The least resistance was to ampicillin (60%). Male gender (p=0.014, 95% CI=1.198-4.813) and history of surgery (p=0.01, 95% CI=1.196-3.740) were found to be significant risk factors for ESBL presence. The findings emphasize that ESBL-producing bacteria are present among patients at the UTH, and that these organisms exhibit co-resistance to several classes of antibiotics.
Subjects/Keywords: Drug resistance, Microbial; Drug resistance in microorganisms
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shawa, M. (2015). Risk factors and Alleles of extended spectrum Beta-Lactamase(ESBL) producing Escherichia coli at the University Teaching Hospital, Zambia. (Thesis). University of Zimbabwe. Retrieved from http://dspace.unza.zm/handle/123456789/4464
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):
Shawa, Misheck. “Risk factors and Alleles of extended spectrum Beta-Lactamase(ESBL) producing Escherichia coli at the University Teaching Hospital, Zambia.” 2015. Thesis, University of Zimbabwe. Accessed March 04, 2021.
http://dspace.unza.zm/handle/123456789/4464.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shawa, Misheck. “Risk factors and Alleles of extended spectrum Beta-Lactamase(ESBL) producing Escherichia coli at the University Teaching Hospital, Zambia.” 2015. Web. 04 Mar 2021.
Vancouver:
Shawa M. Risk factors and Alleles of extended spectrum Beta-Lactamase(ESBL) producing Escherichia coli at the University Teaching Hospital, Zambia. [Internet] [Thesis]. University of Zimbabwe; 2015. [cited 2021 Mar 04].
Available from: http://dspace.unza.zm/handle/123456789/4464.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shawa M. Risk factors and Alleles of extended spectrum Beta-Lactamase(ESBL) producing Escherichia coli at the University Teaching Hospital, Zambia. [Thesis]. University of Zimbabwe; 2015. Available from: http://dspace.unza.zm/handle/123456789/4464
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Stellenbosch University
3.
Fouche, Desire.
Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients.
Degree: MScMedSc, Medicine, 2012, Stellenbosch University
URL: http://hdl.handle.net/10019.1/20079
► ENGLISH ABSTRACT: Background: HIV-positive patients have a significantly weakened immune system which makes them highly susceptible for opportunistic infections, requiring additional treatment. Cryptococcal meningitis and…
(more)
▼ ENGLISH ABSTRACT: Background: HIV-positive patients have a significantly weakened immune system which
makes them highly susceptible for opportunistic infections, requiring additional treatment.
Cryptococcal meningitis and oropharyngeal candidiasis are treated with oral fluconazole. A
great potential for
drug-drug interactions (DDIs) between fluconazole and antiretrovirals
(ARVs), efavirenz, nevirapine, and lopinavir/ritonavir, exists due to interference in common
metabolic pathways. The outcome may result in the development of adverse
drug reactions
or
drug resistance and treatment failure.
Aim: The primary aim of this thesis was to evaluate the effect of fluconazole on the
pharmacokinetics of efavirenz, nevirapine and lopinavir/ritonavir in HIV-infected patients
diagnosed with cryptococcal meningitis or oropharyngeal candidiasis.
Methods: A prospective study was conducted in 80 HIV-positive, treatment experienced
adults (≥18 years old) treated in three different outpatient clinics in the Western Cape region.
Patients were subdivided according to ARV regimen and the use of fluconazole. A sparse
sampling design was used and corresponding ARV serum concentrations were determined by
established HPLC and GC methods. Fluconazole serum concentrations were determined by a
newly developed HPLC method. Patient characteristics, concomitant medications, clinical
test data and ARV serum concentrations were included in a NONMEM generated, onecompartment,
open pharmacometric model with first order elimination to detect any drugdrug
interactions between fluconazole and the studied ARVs. The secondary outcome was to
establish which patient characteristics influence ARV pharmacokinetics.
Results: From 80 outpatients, a total of 276 ARV serum samples (137 efavirenz, 67
nevirapine and 72 lopinavir) were collected for pharmacokinetic evaluation. Efavirenz
clearance was correlated with race and concomitant use of rifampicin. No significant
covariates were established in the nevirapine model. In the lopinavir model, concomitant use
of clotrimazole and the antituberculosis combination isoniazid, pyrazinamide and rifampicin
were identified as significant covariates.
Discussion: No significant effects of fluconazole on the pharmacokinetics of any of the
studied ARVs were observed. Varying efavirenz plasma concentrations in different ethnic
populations may be due to differences in gene expression particularly CYP2B6. Coloured patients had significantly lower efavirenz serum concentrations (56.8% decrease in
clearance), which has not been previously described in the South African context. Although
gender was not a significant covariate in the nevirapine model, female patients tended to have
higher nevirapine serum concentrations. TB treatment in all patients receiving lopinavir
consisted of a combination of isoniazid, pyrazinamide and rifampicin, each with different
effects on CYP isoenzymes. The exact contributing factor of each
drug in the ultimate
decrease in lopinavir clearance (46.4%) can therefore not…
Advisors/Committee Members: Rosenkranz, Bernd, Stellenbosch University. Faculty of Health Sciences. Dept. of Medicine. Pharmacology..
Subjects/Keywords: Pharmacology; Drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fouche, D. (2012). Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/20079
Chicago Manual of Style (16th Edition):
Fouche, Desire. “Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients.” 2012. Masters Thesis, Stellenbosch University. Accessed March 04, 2021.
http://hdl.handle.net/10019.1/20079.
MLA Handbook (7th Edition):
Fouche, Desire. “Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients.” 2012. Web. 04 Mar 2021.
Vancouver:
Fouche D. Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients. [Internet] [Masters thesis]. Stellenbosch University; 2012. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10019.1/20079.
Council of Science Editors:
Fouche D. Drug-drug interactions between antiretrovirals and fluconazole in HIV-infected patients. [Masters Thesis]. Stellenbosch University; 2012. Available from: http://hdl.handle.net/10019.1/20079

University of Saskatchewan
4.
Denton, Alyssa.
CHARACTERIZING DRUG-RESISTANCE IN ADULTS WITH NEW-ONSET EPILEPSY.
Degree: 2020, University of Saskatchewan
URL: http://hdl.handle.net/10388/12955
► Background and objectives: There are very few studies reporting the factors involved in or the rate of drug-resistant epilepsy (DRE) in adults with new-onset epilepsy…
(more)
▼ Background and objectives: There are very few studies reporting the factors involved in or the rate of
drug-resistant epilepsy (DRE) in adults with new-onset epilepsy (NOE). This prospective cohort study characterizes DRE and risk factors in a pure adult cohort with NOE or newly diagnosed epilepsy (NDE). There are very few studies reporting the factors involved in or the rate of DRE in adults with NO and NDE. Methods: Patients were selected from a prospective cohort followed between 2011 and 2018 from the Single Seizure Clinic (SSC) in Saskatoon, SK. The SSC sees patients who experience their first seizure and approximately 30% are diagnosed with epilepsy. We identified the following variables and outcomes in the cohort: age, gender, epilepsy type, seizure onset, etiology, epilepsy syndromes, EEG and imaging outcomes, and the rates of DRE. Inclusion criteria included patients with NO and NDE, age 18 years or older at time of diagnosis, and a minimum 1 year of follow‐up. Results: Ninety-five patients were included, 46 females and 49 males. Median age of onset was 33 years. Of those, 20.0% developed DRE between 2011-2018. Average time between onset and DRE diagnosis was 2.32 years. Bivariate analysis identified age, gender, and etiology as important risk factors for DRE, however these variables failed to be significant in the multivariate model. Discussion: A lower percentage of DRE was identified in this cohort of adults compared to any other published study at present. The majority of patients to develop DRE were diagnosed in the first year of follow up, showing the importance of early characterization and treatment. Similarly, a younger age of onset was shown to be a substantial indicator of the prognosis. Despite a small cohort and insignificant statistical outcomes, our findings might guide the directions of future research in this topic. Significance: The specificity of the cohort along with the outcomes identified in this study contribute valuable information about NOE in adults and the development of DRE. This study has laid the groundwork for not only a larger cohort study to be implemented in the future, but also several other studies to evaluate potential predictors such as specific imaging results as a risk factor for DRE and quality of life assessment through follow-up related to DRE risk.
Advisors/Committee Members: Tellez-Zenteno, Jose, Pena-Sanchez, Juan-Nicolas, Kirk, Andrew, Thorpe, Lilian, Camfield, Peter.
Subjects/Keywords: epilepsy; drug-resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Denton, A. (2020). CHARACTERIZING DRUG-RESISTANCE IN ADULTS WITH NEW-ONSET EPILEPSY. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/12955
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):
Denton, Alyssa. “CHARACTERIZING DRUG-RESISTANCE IN ADULTS WITH NEW-ONSET EPILEPSY.” 2020. Thesis, University of Saskatchewan. Accessed March 04, 2021.
http://hdl.handle.net/10388/12955.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Denton, Alyssa. “CHARACTERIZING DRUG-RESISTANCE IN ADULTS WITH NEW-ONSET EPILEPSY.” 2020. Web. 04 Mar 2021.
Vancouver:
Denton A. CHARACTERIZING DRUG-RESISTANCE IN ADULTS WITH NEW-ONSET EPILEPSY. [Internet] [Thesis]. University of Saskatchewan; 2020. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10388/12955.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Denton A. CHARACTERIZING DRUG-RESISTANCE IN ADULTS WITH NEW-ONSET EPILEPSY. [Thesis]. University of Saskatchewan; 2020. Available from: http://hdl.handle.net/10388/12955
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queens University
5.
McClure, Nathan.
Assessing strategies for managing drug resistance in treatment of infectious disease: insights from queueing theory
.
Degree: Biology, 2013, Queens University
URL: http://hdl.handle.net/1974/8099
► Antimicrobials have been instrumental in the treatment of infectious disease: responsible for worldwide infection control and reductions in disease-induced morbidity, and mortality. However, in every…
(more)
▼ Antimicrobials have been instrumental in the treatment of infectious disease: responsible for worldwide infection control and reductions in disease-induced morbidity, and mortality. However, in every case where new chemotherapeutic agents have been introduced, resistance to them has eventually evolved. Principally, the current strategy for dealing with this problem is to invest heavily in drug development, with the hope that new drugs become available before all existing drugs lose their efficacy. Instead of focusing on the ‘development side’ of the problem, another possible strategy is to invest in methods of slowing evolution of resistance.
We use a novel application of queueing theory to demonstrate that, when comparing equivalent changes in drug development versus evolution management, the latter has a much greater effect on ensuring a continued supply of effective antimicrobial agents. Our results therefore call for a reappraisal of the current emphasis on enhancing drug development as a means of managing resistance.
Subjects/Keywords: drug resistance
;
evolution
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
McClure, N. (2013). Assessing strategies for managing drug resistance in treatment of infectious disease: insights from queueing theory
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/8099
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):
McClure, Nathan. “Assessing strategies for managing drug resistance in treatment of infectious disease: insights from queueing theory
.” 2013. Thesis, Queens University. Accessed March 04, 2021.
http://hdl.handle.net/1974/8099.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
McClure, Nathan. “Assessing strategies for managing drug resistance in treatment of infectious disease: insights from queueing theory
.” 2013. Web. 04 Mar 2021.
Vancouver:
McClure N. Assessing strategies for managing drug resistance in treatment of infectious disease: insights from queueing theory
. [Internet] [Thesis]. Queens University; 2013. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1974/8099.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
McClure N. Assessing strategies for managing drug resistance in treatment of infectious disease: insights from queueing theory
. [Thesis]. Queens University; 2013. Available from: http://hdl.handle.net/1974/8099
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas A&M University
6.
Mousavifard, Seyedhossein.
Targeting a Nrf2/G6PDH Pathway to Reverse Multi-Drug Resistance in Diffuse Large B-Cell Lymphoma.
Degree: PhD, Medical Sciences, 2017, Texas A&M University
URL: http://hdl.handle.net/1969.1/191958
► A leading cause of mortality in diffuse large B-cell lymphoma (DLBCL) patients is the development of resistance to the CHOP regimen, the anthracycline-based chemotherapy consisting…
(more)
▼ A leading cause of mortality in diffuse large B-cell lymphoma (DLBCL) patients is the development of
resistance to the CHOP regimen, the anthracycline-based chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. Our first objective of this work was to investigate the impact of Nuclear factor erythroid–related factor 2 (Nrf2)/ glucose-6-phosphate dehydrogenase (G6PDH) pathway on CHOP-
resistance in DLBCL cell lines. We provide evidence here that a Nrf2/G6PDH pathway plays a role in mediating CHOP-
resistance in DLBCL. We found that CHOP-resistant DLBCL cells expressed both higher Nrf2 and G6PDH activities and lower reactive oxygen (predominantly superoxide) levels than CHOP-sensitive cells. We hypothesized that increased activity of the Nrf2/G6PDH pathway leads to higher GSH production, a more reduced state (lower ROS), and CHOP-
resistance. In support of our hypothesis, direct inhibition of G6PDH or knockdown of Nrf2/G6PDH lowered both NADPH and GSH levels, increased ROS, and reduced tolerance or CHOP-resistant cells to CHOP. We also present evidence that repeated cycles of CHOP treatment select for a small population of Nrf2^High/G6PDH^High/ROS^Low cells that are more tolerant of CHOP and might be responsible for the emergence of chemoresistant tumors. We propose that sensitive Nrf2^Low /G6PDH^Low /ROS^High cells are essentially killed off by CHOP allowing for the selective propagation of the small population of CHOP-resistant Nrf2^High/G6PDH^High/ROS^Low cells, thereby resulting in relapse of lymphoma.
Our second objective was to study rifamycins’ potency at sensitizing
drug resistant cancer cells to chemotherapeutics. We have discovered a novel chemosensitizer (RTI-79, a rifamycinderivative) with a broad spectrum of action that includes ovarian cancer and double and triple hit non-Hodgkin’s lymphoma. RTI-79 is relatively non-toxic and has favorable in vivo safety and pharmacokinetic (PK) profiles. RTI-79 in combination therapies is effective in multiple
drug resistant cancers in mouse models. RTI-79 works by dramatically increasing intracellular reactive oxygen species (ROS), primarily superoxide, through redox cycling. The level of ROS induction is directly correlated with
drug sensitivity. Importantly, RTI-79 also triggers the unfolded protein response (UPR) that results in increased ubiquitination and loss of Nrf2, the primary sensor for intracellular ROS. Thus, RTI-79 both increases ROS and squelches Nrf2’s ability to respond to ROS. This unique mechanism provides a broad and novel approach for the very safe application of RTI-79, and other rifamycins, in treating
drug resistant cancers.
We also showed that RTI-79 acts to increase the oxidative state in chemoresistant cancer cells by inducing superoxide (O2-) and downregulating the Nrf2/G6PDH/NADPH/GSH pathway. RTI-79 also increased the ubiquitination state of several mitochondrial chaperone proteins (mtDnaJ [HSP40]), HSP60, HSP70mt [mortalin]) and decreased activated CREB, which are known to play roles in mitochondrial unfolded…
Advisors/Committee Members: Maxwell, Steve (advisor), Zimmer, Warren (advisor), Sacchettini, James C. (committee member), Sitcheran, Raquel (committee member), Threadgill, David W. (committee member).
Subjects/Keywords: Cancer; drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mousavifard, S. (2017). Targeting a Nrf2/G6PDH Pathway to Reverse Multi-Drug Resistance in Diffuse Large B-Cell Lymphoma. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/191958
Chicago Manual of Style (16th Edition):
Mousavifard, Seyedhossein. “Targeting a Nrf2/G6PDH Pathway to Reverse Multi-Drug Resistance in Diffuse Large B-Cell Lymphoma.” 2017. Doctoral Dissertation, Texas A&M University. Accessed March 04, 2021.
http://hdl.handle.net/1969.1/191958.
MLA Handbook (7th Edition):
Mousavifard, Seyedhossein. “Targeting a Nrf2/G6PDH Pathway to Reverse Multi-Drug Resistance in Diffuse Large B-Cell Lymphoma.” 2017. Web. 04 Mar 2021.
Vancouver:
Mousavifard S. Targeting a Nrf2/G6PDH Pathway to Reverse Multi-Drug Resistance in Diffuse Large B-Cell Lymphoma. [Internet] [Doctoral dissertation]. Texas A&M University; 2017. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/1969.1/191958.
Council of Science Editors:
Mousavifard S. Targeting a Nrf2/G6PDH Pathway to Reverse Multi-Drug Resistance in Diffuse Large B-Cell Lymphoma. [Doctoral Dissertation]. Texas A&M University; 2017. Available from: http://hdl.handle.net/1969.1/191958

University of Illinois – Urbana-Champaign
7.
Petronikolou, Nektaria.
Structural and biochemical studies of enzymes involved in the biosynthesis of value-added products.
Degree: PhD, Biochemistry, 2018, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/101259
► Enzymes have been used for decades for the industrial production of high value chemicals such as food additives, antibiotics and other pharmaceutical products. However, in…
(more)
▼ Enzymes have been used for decades for the industrial production of high value chemicals such as food additives, antibiotics and other pharmaceutical products. However, in recent years the significant advances in biocatalyst development have led to a rise in the number of commodity chemicals being produced by enzymes instead of extraction from plants or chemical synthesis. Such products include biodiesel and wax esters.
For this industrial exploitation of enzymes, it is vital to have an extensive understanding of how the desired enzymes work, including what the enzymes’ substrate preferences and stability are. This knowledge comes from the structural and biochemical characterization of these biocatalysts, and this is the scope of this dissertation; to broaden our knowledge and understanding of enzymes that are involved in the biosynthesis of value-added products, such as biodiesel and drugs.
Biodiesel is a mixture of long chain fatty acid alkyl esters (FAAEs), produced mainly by the transesterification of fatty acids derived from vegetable oils and animal fats. In recent years, biodiesel has emerged as a viable resource for utilization in green energy production. However, current production processes utilize methods that are cost ineffective and generate waste byproducts. Recent progress in the field makes use of biocatalysts that are effective in diverting products from primary metabolism to yield fatty acid methyl and ethyl esters in bacterial systems (as well as other commodity chemicals). Two of these enzymes have been the focus of my study: a fatty acid O-methyltransferase (FAMT) from Mycobacterium marinum (MmFAMT), and a bifunctional wax ester synthase/diacylglycerol acyl-transferase (WS/DGAT) from Marinobacter aquaeolei VT8 (Ma-WS/DGAT).
In Chapter 1, I present the first kinetic and structural characterization of a mycobacterial fatty acid O-methyltransferase (MmFAMT) previously utilized for the production of biodiesel in E. coli. The structure revealed unexpected similarity with methyltransferases from plant natural product metabolism, and an active-site cavity that can accommodate fatty acids up to 12-14 carbons long. Our results provide the framework for further optimization of an in vivo system that utilizes MmFAMT for production of biodiesel.
In Chapter 2, I discuss the structure of a bifunctional wax ester synthase/diacylglycerol acyl-transferase (Ma-WS/DGAT), which is to our knowledge the first structure for any member of this enzyme family to date. Wax esters (WE) are esters of long chain fatty acids and long chain alcohols and have widely been used in cosmetics, lubricants, candles and the food industry. In addition, WE that consist of medium chain fatty acids and ethanol (fatty acid ethyl esters, FAEEs) are biodiesel. Today, there is a strong demand for the development of a large-scale process for the production of low cost WE. The structure may facilitate future engineering efforts aiming at the optimization of this biocatalyst towards production of desired wax esters for industrial use.
In…
Advisors/Committee Members: Nair, Satish K (advisor), Nair, Satish K (Committee Chair), Cronan, John E (committee member), Zhao, Huimin (committee member), Jin, Hong (committee member).
Subjects/Keywords: biocatalysis; biofuels; drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Petronikolou, N. (2018). Structural and biochemical studies of enzymes involved in the biosynthesis of value-added products. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101259
Chicago Manual of Style (16th Edition):
Petronikolou, Nektaria. “Structural and biochemical studies of enzymes involved in the biosynthesis of value-added products.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed March 04, 2021.
http://hdl.handle.net/2142/101259.
MLA Handbook (7th Edition):
Petronikolou, Nektaria. “Structural and biochemical studies of enzymes involved in the biosynthesis of value-added products.” 2018. Web. 04 Mar 2021.
Vancouver:
Petronikolou N. Structural and biochemical studies of enzymes involved in the biosynthesis of value-added products. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2142/101259.
Council of Science Editors:
Petronikolou N. Structural and biochemical studies of enzymes involved in the biosynthesis of value-added products. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101259

University of Oxford
8.
Peto, Leon.
The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome.
Degree: PhD, 2020, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:a506f2f7-bb4f-402d-8b61-2eefbfceb9e7
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808374
► The gut is a major reservoir of human pathogens, and increasing antimicrobial resistance (AMR) in these organisms is an important problem. Selection of AMR by…
(more)
▼ The gut is a major reservoir of human pathogens, and increasing antimicrobial resistance (AMR) in these organisms is an important problem. Selection of AMR by antimicrobials occurs against a background of disruption in a rich bacterial ecosystem, the gut microbiome. Our understanding of this has recently been transformed by new techniques, such as metagenomic sequencing, that can describe the whole community and directly detect AMR genes. Efforts to control AMR would be greatly helped by reliable measures of the impacts of different antimicrobials on the gut microbiome, but these are generally not available. The aim of this thesis is to address this problem. A significant limitation of using metagenomic sequencing to study AMR is its inability to detect important resistance genes present at low abundance, and in initial work I explore methods to improve the detection of these using plasmid DNA extraction and selective culture-enrichment. These approaches improve the limit of detection of specific resistance mechanisms, but prove unsuitable for use in a quantitative assay. I then analyse data from an observational study that I conducted, which recorded antimicrobial exposures and collected stool samples from hospital patients and healthy volunteers. Using multiple regression models with data from metagenomic sequencing, I estimate the effects of specific antimicrobial exposures on global microbiome diversity, the abundance of specific taxa, and the abundance of specific classes of AMR genes. The study utilised both cross-sectional and longitudinal sampling frames, which I analyse separately, providing independent estimates that are supportive of one another. These data allow the direct, quantitative, comparison of many different antimicrobials used in the study. The work also develops approaches to the analysis of these types of observational data that could be used in future studies.
Subjects/Keywords: Drug resistance in microorganisms
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Peto, L. (2020). The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:a506f2f7-bb4f-402d-8b61-2eefbfceb9e7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808374
Chicago Manual of Style (16th Edition):
Peto, Leon. “The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome.” 2020. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:a506f2f7-bb4f-402d-8b61-2eefbfceb9e7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808374.
MLA Handbook (7th Edition):
Peto, Leon. “The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome.” 2020. Web. 04 Mar 2021.
Vancouver:
Peto L. The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome. [Internet] [Doctoral dissertation]. University of Oxford; 2020. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:a506f2f7-bb4f-402d-8b61-2eefbfceb9e7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808374.
Council of Science Editors:
Peto L. The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome. [Doctoral Dissertation]. University of Oxford; 2020. Available from: http://ora.ox.ac.uk/objects/uuid:a506f2f7-bb4f-402d-8b61-2eefbfceb9e7 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808374

Penn State University
9.
Bulathsinghala, Marie S.
Regulation of Drug Resistance by Ikaros.
Degree: 2015, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/25617
► Acute leukemia is the most common form of cancer in the pediatric population, accounting for nearly one third of all pediatric malignancies. Survival rates for…
(more)
▼ Acute leukemia is the most common form of cancer in the pediatric population, accounting for nearly one third of all pediatric malignancies. Survival rates for pediatric leukemia have improved dramatically over the last 40 years and the combined 5-year survival rate has risen from less than 20% in the late 1960s to an estimated overall survival rate of greater than 85% today. However, despite the remarkable advancements in treatment therapies, the prognosis for high-risk patients—those who relapse, or fail to achieve post induction remission—remains poor. Treatment failure is the number one cause of relapse, making
drug resistance a hallmark of high-risk leukemia. Sadly, the survival rate for the 25% of children who relapse is less than 30%, underscoring the need for a better understanding of the mechanisms mediating
drug resistance and treatment failure, such that more efficacious treatment regimens can be developed.
Recently, large scale genome-wide analyses of genetic alterations in leukemia have established IKZF1 (also known as ZNFN1A1), the gene encoding IKAROS, as one of the most clinically relevant prognostic markers in high-risk precursor-B cell Acute Lymphoblastic Leukemia (ALL). IKAROS is a sequence-specific DNA binding protein essential for normal hematopoiesis and participates in a complex network of interactions to recruit chromatin-modifying machines to gene regulatory regions promoting their transcriptional activation or repression via chromatin remodeling. Studies in mice have established IKAROS as a master regulator of lymphoid specification and a potent tumor suppressor in leukemia. Ongoing research has demonstrated that IKAROS binds and regulates thousands of genes involved in many different cellular processes. Mutations or deletions in IKZF1 have been consistently associated with high-risk leukemia, and interestingly, IKZF1 was the only gene for which mutations and deletions were found to be useful in predicting a poor response to therapy. What is not well understood, however, is the precise mechanism through which the loss of Ikaros function contributes to
drug resistance and treatment failure.
The absence and/or inactivation of IKAROS is highly associated with leukemia that is resistant to current chemotherapy agents and has a poor prognosis. Evidence suggests that even modest changes in IKAROS function, resulting from defects in a single IKAROS allele (haploinsufficiency), aids in the progression of leukemic transformation and results in increased risk of relapse. Our main goal was to understand the role of IKAROS in high-risk,
drug-resistant leukemia. To accomplish this objective, we studied IKAROS-mediated regulation of genes involved in the folate pathway as well as genes essential to the inhibitory effects and metabolism of standard chemotherapeutics used in the treatment of ALL. We hypothesized that IKAROS regulates the sensitivity of leukemia cells to chemotherapy and that restoration of IKAROS function would inhibit leukemic growth and increase sensitivity to chemotherapy.
To…
Advisors/Committee Members: Sinisa Dovat, Dissertation Advisor/Co-Advisor, Sinisa Dovat, Committee Chair/Co-Chair, John Warren Wills, Committee Member, Barbara Miller, Committee Member, Gregory Yochum, Committee Member.
Subjects/Keywords: Leukemia; drug-resistance; Ikaros
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bulathsinghala, M. S. (2015). Regulation of Drug Resistance by Ikaros. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/25617
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):
Bulathsinghala, Marie S. “Regulation of Drug Resistance by Ikaros.” 2015. Thesis, Penn State University. Accessed March 04, 2021.
https://submit-etda.libraries.psu.edu/catalog/25617.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bulathsinghala, Marie S. “Regulation of Drug Resistance by Ikaros.” 2015. Web. 04 Mar 2021.
Vancouver:
Bulathsinghala MS. Regulation of Drug Resistance by Ikaros. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Mar 04].
Available from: https://submit-etda.libraries.psu.edu/catalog/25617.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bulathsinghala MS. Regulation of Drug Resistance by Ikaros. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/25617
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Waterloo
10.
Dekker, Heather.
Characterising changes in adhesion and enzyme activity related to drug resistance in colon cancer cells.
Degree: 2018, University of Waterloo
URL: http://hdl.handle.net/10012/14278
► Metastatic colorectal cancer is often fatal, and drug resistance to chemotherapeutic agents is one of the primary contributing factors to this lethality. Drug resistance arises…
(more)
▼ Metastatic colorectal cancer is often fatal, and drug resistance to chemotherapeutic agents is one of the primary contributing factors to this lethality. Drug resistance arises from exposure to chemotherapies, and it can be mediated through a variety of mechanisms. One of these mechanisms is alteration of enzymes within the cancer cells to affect the processing or removal of the drug. Carboxylesterase is an example of an enzyme that converts irinotecan, a drug used in metastatic colorectal cancer treatments, into the active metabolite SN-38. Carboxylesterase enzymes are found in high quantities in both the liver and intestinal cells. The presence of carboxylesterase in intestinal and liver cells is an important consideration in the processing of colorectal cancer treatments. Glutathione S-transferase is another enzyme that has been implicated in drug resistance because of its ability to conjugate reduced glutathione to xenobiotic substances, facilitating their removal. Additionally, drug resistance can affect the behaviours of cells. Drug-resistant cells can exhibit changes in their motility and aggressiveness compared to drug-sensitive cells. In this study I investigated cellular behavioural changes in SN-38-resistant colon cancer cells compared to their SN-38-sensitive counterparts. In addition to behavioural changes, I also sought to determine if elevations in carboxylesterase and glutathione S-transferase enzymes were contributing to the drug resistance in these colon cancer cells.
Subjects/Keywords: drug resistance; colorectal cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dekker, H. (2018). Characterising changes in adhesion and enzyme activity related to drug resistance in colon cancer cells. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/14278
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):
Dekker, Heather. “Characterising changes in adhesion and enzyme activity related to drug resistance in colon cancer cells.” 2018. Thesis, University of Waterloo. Accessed March 04, 2021.
http://hdl.handle.net/10012/14278.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dekker, Heather. “Characterising changes in adhesion and enzyme activity related to drug resistance in colon cancer cells.” 2018. Web. 04 Mar 2021.
Vancouver:
Dekker H. Characterising changes in adhesion and enzyme activity related to drug resistance in colon cancer cells. [Internet] [Thesis]. University of Waterloo; 2018. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10012/14278.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dekker H. Characterising changes in adhesion and enzyme activity related to drug resistance in colon cancer cells. [Thesis]. University of Waterloo; 2018. Available from: http://hdl.handle.net/10012/14278
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
11.
Chen, Xiangyun.
Novel Self-assemble nanoparticles to inhibit cancer growth -effects on ER stress, autophagy, and multidrug resistance by a small molecule.
Degree: 2015, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/27488
► Drug resistance remains challenging for modern cancer therapy methods including surgery, radiation, and small molecule chemotherapy. Nanotechnology has emerged as promising strategy to overcome impasses…
(more)
▼ Drug resistance remains challenging for modern cancer therapy methods including surgery, radiation, and small molecule chemotherapy. Nanotechnology has emerged as promising strategy to overcome impasses in several science branches. Liposome, polymer sphere, carbon nanosphere, and metallic particles have been used for nanomedicine development. Doxil, pegylated liposomal doxorubicin, is the first FDA approved nanodrug to treat cancers in 1995. Doxorubicin is believed to confer cytotoxicity to cancer cells by 1) intercalation in DNA to disrupt topoisomerase II-mediated DNA repair and 2) generating free radicals to damage cell membrane, DNA, and proteins. Compared to free doxorubicin, Doxil greatly improves the pharmacokinetics of doxorubicin, reduces cardiotoxicity, and increases efficacy by passive targeting. However, Doxil is constantly on FDA’s shortage list. Due to manufacture complexity, even the FDA approved generic “Doxil” is costly to make. Therefore, I want to invent a high efficient and low toxicity nanomedicine that is simple to prepare and easy to scale up.
In this dissertation, I present a novel strategy for preparing nanoparticles that are effective for
drug resistant cancers. Among a series of β-carboline derived small molecules, Nano-6E kills cancer cells in micromolar range while is safe for normal human fibroblast (NHF) cells. Nano-6E accumulates more and/or metabolizes slower in cancerous U2OS cells compare to NHF cells. In addition, Nano-6E spontaneously assembles into nanoparticles. Nano-6E induces severe ER stress, disrupts cytoskeleton, and inhibits autophagy in U2OS cells. Interestingly, Nano-6E disturbs cytosolic calcium and affects autophagosome lysosome fusion. To achieve effective inhibition of multidrug resistant tumors, I combined Nano-6E with many clinical used anticancer drugs. Nano-6E and doxorubicin showed synergistic cytotoxicity to multi-
drug resistant uterine sarcoma MES-SA/Dx5 cells. Dox-6E activates p53 and leads to apoptosis in MES-SA/Dx5 cells. Further investigation of Nano-6E and doxorubicin reveals that doxorubicin and Nano-6E forms dual-
drug nano-particles range from 3.4 nm to 60.1 nm in diameters. The optimized size range enable Dox-6E particles to demonstrate enhanced permeation and retention effects, leading to 1) extend blood circulation time of doxorubicin; 2) accumulate more in tumor tissue and less in heart and kidney; and 3) significantly inhibit tumor growth in xenograft model of MES-SA/Dx5.
In summary, I have designed a novel way to prepare nanoparticles adding another layer to current big molecular based nanotechnology. The self-assembled Dox-6E particles are high efficacy, low toxicity, and easy to prepare.
Advisors/Committee Members: Yanming Wang, Dissertation Advisor/Co-Advisor, Douglas Cavener, Committee Chair/Co-Chair, Zhi Chun Lai, Committee Member, Lu Bai, Committee Member, Gavin Peter Robertson, Special Member.
Subjects/Keywords: Nanomedicine; Multi-drug resistance; cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chen, X. (2015). Novel Self-assemble nanoparticles to inhibit cancer growth -effects on ER stress, autophagy, and multidrug resistance by a small molecule. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/27488
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):
Chen, Xiangyun. “Novel Self-assemble nanoparticles to inhibit cancer growth -effects on ER stress, autophagy, and multidrug resistance by a small molecule.” 2015. Thesis, Penn State University. Accessed March 04, 2021.
https://submit-etda.libraries.psu.edu/catalog/27488.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chen, Xiangyun. “Novel Self-assemble nanoparticles to inhibit cancer growth -effects on ER stress, autophagy, and multidrug resistance by a small molecule.” 2015. Web. 04 Mar 2021.
Vancouver:
Chen X. Novel Self-assemble nanoparticles to inhibit cancer growth -effects on ER stress, autophagy, and multidrug resistance by a small molecule. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Mar 04].
Available from: https://submit-etda.libraries.psu.edu/catalog/27488.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chen X. Novel Self-assemble nanoparticles to inhibit cancer growth -effects on ER stress, autophagy, and multidrug resistance by a small molecule. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/27488
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal
12.
Chimukangara, Benjamin.
The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa.
Degree: 2018, University of KwaZulu-Natal
URL: https://researchspace.ukzn.ac.za/handle/10413/18048
► HIV drug resistance (HIVDR) present prior to initiating or re-initiating antiretroviral therapy (ART), is known as pretreatment drug resistance (PDR). Conventionally, PDR is detected by…
(more)
▼ HIV
drug resistance (HIVDR) present prior to initiating or re-initiating antiretroviral therapy (ART), is known as pretreatment
drug resistance (PDR). Conventionally, PDR is detected by Sanger sequencing.
Drug resistant minority variants (DRMVs) that are not reliably detected by Sanger sequencing can be detected by next generation sequencing. The aims of this research were to assess levels of PDR in HIV hyper-endemic areas (with high HIV incidence and prevalence) in KwaZulu-Natal (KZN) province, trends of PDR in South Africa, and the impact of DRMVs on ART. To assess PDR in adults from KZN hyper-endemic areas, 1845 sequences were analyzed from two population-based HIV surveillance studies; a longitudinal HIV surveillance programme in
northern KZN (2013-2014), and the HIV Incidence Provincial Surveillance System (HIPSS) in central KZN (2014-2015). Overall, 182/1845 (10.0%) had NNRTI-PDR mutations, and when analyzed by study year, NNRTI-PDR was 10.2% (CI:7.5-12.9) for the HIPSS study in 2014. To assess PDR trends in South Africa, 6880 HIV-1 sequences were collated from 38 datasets of ART-naïve adults (2000-2016). Increasing levels of PDR were observed, most marked from 2010. Crude pooled prevalence of NNRTI-PDR reached 10% in 2014, with a 1.18-fold (CI:1.13- 1.23) annual increase (p<0.001), consistent with findings from the HIPSS data. This provided the first evidence of high-level NNRTI-PDR in KZN and South Africa, supporting the transition to dolutegravir in standard first-line ART, as recommended by the World Health Organization when NNRTI-PDR reaches ≥10%. A case-control (2:1) study in HIV/TB co-infected adult patients was done to assess the impact of DRMVs at different thresholds. Cases were patients that initiated ART and had viral loads ≥1000 copies/mL after ≥6 months on ART, and controls were those that initiated ART and achieved virologic suppression through 24 months. Pre-ART NNRTI-
resistance was associated with ART failure. NGS improved detection of HIVDR at lower thresholds, but reduced the specificity of identifying patients at risk of virologic failure, with the specificity reducing from 97% (CI:92-99) at 20% threshold, to 79% (CI:71-86) at 2% threshold. In all, the findings presented in this thesis provide a broad message about the need to improve quality in HIV prevention and treatment services.
Advisors/Committee Members: De Oliveira, Tulio Paiva n Andrade. (advisor), Naidoo, Kogieleum. (advisor), Samuel, Reshmi. (advisor).
Subjects/Keywords: Pretreatment HIV drug resistance - Adults - South Africa.; Pretreatment HIV drug resistance - Epidemiology.; Pretreatement HIV drug resistance - Impact.; HIV drug resistance.
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chimukangara, B. (2018). The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/18048
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):
Chimukangara, Benjamin. “The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa.” 2018. Thesis, University of KwaZulu-Natal. Accessed March 04, 2021.
https://researchspace.ukzn.ac.za/handle/10413/18048.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chimukangara, Benjamin. “The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa.” 2018. Web. 04 Mar 2021.
Vancouver:
Chimukangara B. The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa. [Internet] [Thesis]. University of KwaZulu-Natal; 2018. [cited 2021 Mar 04].
Available from: https://researchspace.ukzn.ac.za/handle/10413/18048.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chimukangara B. The epidemiology and impact of pretreatment HIV drug resistance in adults in South Africa. [Thesis]. University of KwaZulu-Natal; 2018. Available from: https://researchspace.ukzn.ac.za/handle/10413/18048
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Addis Ababa University
13.
Ahmed, Esmael.
Drug resistance pattern of Mycobacterium tuberculosis and its association with patients` Knowledge, Attitude and Practice towards tuberculosis in Eastern Amhara Region
.
Degree: 2012, Addis Ababa University
URL: http://etd.aau.edu.et/dspace/handle/123456789/3214
► Background: Tuberculosis (TB) remains a serious public health problem, worsened by the emergence and spread of drug resistance particularly multi-drug resistance that threat global TB…
(more)
▼ Background: Tuberculosis (TB) remains a serious public health problem, worsened by the
emergence and spread of
drug resistance particularly multi-
drug resistance that threat global TB
control. Data obtained from KAP survey is essential to plan, implement and evaluate Advocacy,
Communication and Social Mobilization (ACSM) work.
Objectives: The aim of this study was to assess the magnitude of
drug resistance pattern of
M.tuberculosis, knowledge, perception and practice of patients` towards TB in Eastern Amhara
Region, North East Ethiopia.
Methods: A cross sectional survey was conducted among new and re-treatment patients (age >
18 years old) from September 2010 to February 2011. A structure and pre-validate
questionnaires was used to collect data. Primary isolation and DST were carried out on egg based
LJ media using indirect proportion method. Chi-Square and multivariate logistic regression was
used.
Results: Out of 230 study participants for DST, 165 were new cases while 65 were previously
treated cases. From these, 66.5% of isolates were sensitive and 4.4%
resistance to four first line
anti-tuberculosis drugs (HRSE) while the remaining 33.5% was
resistance to at least for single
drug. MDR-TB was detected in 6.5 % isolates, of which 4.4% were
resistance to all four first
line drugs. Overall
resistance to S, R, H and E was found in 27 % (62), 10 % (23), 17.8 % (41),
and 6.5 % (15) respectively. Mono
resistance was found in 17.4 % (40) of all isolates
Among new cases primary
drug resistance for one or more drugs was observed in 23.6 % (39)
cases. Primary MDR-TB was found in 3 (1.81%) cases. Similarly among previously treated cases
resistance to any
drug was found in 58.5 % (38) cases. MDR-TB in previously treated cases was
found in 18.46 % (12) Cases; the highest being in failure cases 9.23% (6).
More over the mean and median knowledge score of respondents about PTB was 6.81 and 7
respectively. Majority (53.6%) of study subjects had poor knowledge score, feels not well
informed about TB and had several misconceptions that need to be clarified. Majority (66.6%) of
xv
study subjects heard about TB for the first time from health workers. Of study participants,
79.9% mentioned that TB transmits by respiratory droplets through coughing and sneezing and
prevents by covering mouth and nose (66.6%). The four common symptoms mentioned by
respondents were cough (65.6%), weight loss (33.2%), cough > = 2 weeks (32.7%) and shortness
of breath (29.4%). About half of respondent not knew current free cost of TB diagnosis and
treatment. Majority of respondents also worried about the disease due to it might transmits to
their family, might not be cure, social interact (fear of stigma) and unable to do work. Cost (69.9
%) and difficulties in transportation (54.5 %) mentioned as the main reason for their delaines to
seeking care.
Previous
drug exposure and 1+ bacterial load independently contribute for the development of
drug resistance TB strains. Similarly Illiteracy, rural residence, non-previous history of
contracting TB, experiencing…
Advisors/Committee Members: Mr. Kassue Desta (BSc, MSc (advisor).
Subjects/Keywords: Mycobacterium tuberculosis;
Drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ahmed, E. (2012). Drug resistance pattern of Mycobacterium tuberculosis and its association with patients` Knowledge, Attitude and Practice towards tuberculosis in Eastern Amhara Region
. (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/3214
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):
Ahmed, Esmael. “Drug resistance pattern of Mycobacterium tuberculosis and its association with patients` Knowledge, Attitude and Practice towards tuberculosis in Eastern Amhara Region
.” 2012. Thesis, Addis Ababa University. Accessed March 04, 2021.
http://etd.aau.edu.et/dspace/handle/123456789/3214.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ahmed, Esmael. “Drug resistance pattern of Mycobacterium tuberculosis and its association with patients` Knowledge, Attitude and Practice towards tuberculosis in Eastern Amhara Region
.” 2012. Web. 04 Mar 2021.
Vancouver:
Ahmed E. Drug resistance pattern of Mycobacterium tuberculosis and its association with patients` Knowledge, Attitude and Practice towards tuberculosis in Eastern Amhara Region
. [Internet] [Thesis]. Addis Ababa University; 2012. [cited 2021 Mar 04].
Available from: http://etd.aau.edu.et/dspace/handle/123456789/3214.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ahmed E. Drug resistance pattern of Mycobacterium tuberculosis and its association with patients` Knowledge, Attitude and Practice towards tuberculosis in Eastern Amhara Region
. [Thesis]. Addis Ababa University; 2012. Available from: http://etd.aau.edu.et/dspace/handle/123456789/3214
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Addis Ababa University
14.
BERHAN, MENGISTE.
ANTIPLASMODIAL ACTIVITY OF EXTRACTS FROM DODONAEA ANGUSTIFOLIA L.F. AND BERSAMA ABYSSINICA FRESEN AGAINST PLASMODIUM BERGHEI IN MICE MODEL
.
Degree: 2008, Addis Ababa University
URL: http://etd.aau.edu.et/dspace/handle/123456789/6503
► The seed of Dodonaea angustifolia and root bark of Bersama abyssinica are traditionally used for the treatment/prophylaxis of malaria in some malarous areas in Ethiopia.…
(more)
▼ The seed of Dodonaea angustifolia and root bark of Bersama abyssinica are traditionally used for the treatment/prophylaxis of malaria in some malarous areas in Ethiopia. The aim of this study is to evaluate antiplasmodial activity and study acute toxicity of Dodonaea angustifolia and Bersama abyssinica in P. berghei infected mice. In the present study, aqueous and methanol extracts of D. angustifolia and B. abyssinica were investigated for their antimalarial activity using Peters’ 4-day suppressive test against P. berghei infection in mice. The crude extracts and the fractions of the most active extract were orally administered to screen their antimalarial properties. The extracts significantly inhibited parasitemia and prevented PCV fall (p <0.05) dose-dependently. They increased the survival time of the infected mice. However, the extracts from both plants did not prevent body weight loss. The aqueous extract of D. angustifolia was found to be most active producing 35.79% chemosuppression. From this extract, three fractions were produced and tested in vivo against P. berghei in mice. The butanol fraction was found to be the most active producing percentage inhibition of 48.6% at 100 mg/kg. This fraction was also found to prevent PCV, body weight and temperature reduction significantly. The test substances showed only low toxicity (LD50=5044 mg/kg for B. abyssinica and no mortality for D. angustifolia up to 4500 mg/kg). The results obtained from the present work support the traditional use of these plants for treatment of malaria. Key words: Malaria, Drug resistance, Dodonaea angustifolia, Bersama abyssinica, Plasmodium berghei and
Subjects/Keywords: Malaria; Drug resistance; Dodonaea angustifolia
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
BERHAN, M. (2008). ANTIPLASMODIAL ACTIVITY OF EXTRACTS FROM DODONAEA ANGUSTIFOLIA L.F. AND BERSAMA ABYSSINICA FRESEN AGAINST PLASMODIUM BERGHEI IN MICE MODEL
. (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/6503
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):
BERHAN, MENGISTE. “ANTIPLASMODIAL ACTIVITY OF EXTRACTS FROM DODONAEA ANGUSTIFOLIA L.F. AND BERSAMA ABYSSINICA FRESEN AGAINST PLASMODIUM BERGHEI IN MICE MODEL
.” 2008. Thesis, Addis Ababa University. Accessed March 04, 2021.
http://etd.aau.edu.et/dspace/handle/123456789/6503.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
BERHAN, MENGISTE. “ANTIPLASMODIAL ACTIVITY OF EXTRACTS FROM DODONAEA ANGUSTIFOLIA L.F. AND BERSAMA ABYSSINICA FRESEN AGAINST PLASMODIUM BERGHEI IN MICE MODEL
.” 2008. Web. 04 Mar 2021.
Vancouver:
BERHAN M. ANTIPLASMODIAL ACTIVITY OF EXTRACTS FROM DODONAEA ANGUSTIFOLIA L.F. AND BERSAMA ABYSSINICA FRESEN AGAINST PLASMODIUM BERGHEI IN MICE MODEL
. [Internet] [Thesis]. Addis Ababa University; 2008. [cited 2021 Mar 04].
Available from: http://etd.aau.edu.et/dspace/handle/123456789/6503.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
BERHAN M. ANTIPLASMODIAL ACTIVITY OF EXTRACTS FROM DODONAEA ANGUSTIFOLIA L.F. AND BERSAMA ABYSSINICA FRESEN AGAINST PLASMODIUM BERGHEI IN MICE MODEL
. [Thesis]. Addis Ababa University; 2008. Available from: http://etd.aau.edu.et/dspace/handle/123456789/6503
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Colorado State University
15.
Achenbach, Jenna Elizabeth.
Avian influenza A virus transmission and the emergence of drug resistance.
Degree: PhD, Microbiology, Immunology, and Pathology, 2011, Colorado State University
URL: http://hdl.handle.net/10217/70430
► As avian influenza A viruses (AIV) continue to circulate worldwide both naturally, within the reservoir host of wild waterfowl, and cross species barriers, eventually establishing…
(more)
▼ As avian influenza A viruses (AIV) continue to circulate worldwide both naturally, within the reservoir host of wild waterfowl, and cross species barriers, eventually establishing itself in new host species, it is imperative to study the natural reservoir in respect to virus change and transmissibility. This dissertation will focus on the transmissibility of a mallard virus from mallards to other wild and domestic species as well as elucidate the possible outcomes of oseltamivir contamination in the environment and its effect on influenza A virus infected mallards. Low pathogenicity (LP) AIVs of the H5N2 and H7N3 subtypes were utilized to evaluate the ability of transmission of a mallard derived virus to other species present in a co-habitation (barnyard) scenario. Other species in contact with the mallards were chickens, blackbirds, rats, and pigeons. Viral replication was assessed directly from ducks in the barnyard with assessment of the other animals in the barnyard through sero-conversion. Additional animals of each species were directly inoculated with these two viruses and assessed for viral replication. The H5N2 virus was transmitted to other ducks and chickens in the barnyard through either direct or environmental contamination, but not to rats or blackbirds. The H7N3 virus was transmitted to other ducks, chickens, pigeons, and rats. Chickens and blackbirds directly inoculated with both virus strains shed significant amount of virus and seroconverted, but rats and pigeons (except for one pigeon) failed to shed virus but did develop antiviral antibodies. Knowing that both mallard viruses can directly transmit without adaptation, show the mallard to be a good model to further evaluate the outcome of oseltamivir contamination in the environment and its effect on AIV infected mallards. The environment has been shown to be contaminated with significant amounts of oseltamivir carboxylate (OC) in an area of high
drug prescription use. We analyzed the outcomes of AIV in infected mallards when they have access to OC in their drinking water. Two separate LPAIV H5N2 viruses were tested for their ability to mutate under
drug pressure. One H5N2 virus did not demonstrate any altered sequence after 7-10 days of
drug access and infection. The other H5N2 virus did show mutations in the neuraminidase gene that led to an increase in
resistance to oseltamivir caused by a specific mutation at E119V. This resistant virus was further evaluated for its ability to transmit between infected and naïve mallards. While the resistant virus did transmit duck to duck, the mutation at position 119 was not detected after challenge or transmission showing instability of this mutation. This could either be a reversion to wild-type or possibly the low level presence of wild-type present in the resistant strain stock that outcompeted with the mutant strain to succeed in the host. This shows, that in these duck experiments, the E119V mutation is not stable in the absence of
drug pressure and unlikely to succeed in the host.
Advisors/Committee Members: Bowen, Richard A. (advisor), Landolt, Gabriele A. (committee member), Avery, Anne C. (committee member), Frye, Melinda A. (committee member).
Subjects/Keywords: avian; resistance; influenza; drug
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Achenbach, J. E. (2011). Avian influenza A virus transmission and the emergence of drug resistance. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/70430
Chicago Manual of Style (16th Edition):
Achenbach, Jenna Elizabeth. “Avian influenza A virus transmission and the emergence of drug resistance.” 2011. Doctoral Dissertation, Colorado State University. Accessed March 04, 2021.
http://hdl.handle.net/10217/70430.
MLA Handbook (7th Edition):
Achenbach, Jenna Elizabeth. “Avian influenza A virus transmission and the emergence of drug resistance.” 2011. Web. 04 Mar 2021.
Vancouver:
Achenbach JE. Avian influenza A virus transmission and the emergence of drug resistance. [Internet] [Doctoral dissertation]. Colorado State University; 2011. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10217/70430.
Council of Science Editors:
Achenbach JE. Avian influenza A virus transmission and the emergence of drug resistance. [Doctoral Dissertation]. Colorado State University; 2011. Available from: http://hdl.handle.net/10217/70430

University of Debrecen
16.
Géczy, Katalin Éva.
Aminoglikozidokkal szembeni rezisztenciamechanizmusok baktériumokban
.
Degree: DE – TEK – Természettudományi és Technológiai Kar – Biológiai és Ökológiai Intézet, 2013, University of Debrecen
URL: http://hdl.handle.net/2437/177289
► Az aminoglikozidok leginkább a gram-negatív aerob baktériumokkal szemben hatásosak. A baktériumok az aminoglikozidok szelekciós nyomása miatt idővel rezisztenssé váltak vagy válhatnak, emiatt a különböző rezisztenciamechanizmusok…
(more)
▼ Az aminoglikozidok leginkább a gram-negatív aerob baktériumokkal szemben hatásosak. A baktériumok az aminoglikozidok szelekciós nyomása miatt idővel rezisztenssé váltak vagy válhatnak, emiatt a különböző rezisztenciamechanizmusok megértése elengedhetetlen a rezisztens baktériumok ellen biztosan használó antibiotikus terápiák kifejlesztéséhez. A jelenleg ismert mechanizmusok közé tartozik (i) az aminoglikozidot inaktiváló transzferáz enzimek termelése, (ii) az aminoglikozidok sejtbe jutásának és szétterjedésének megakadályozása, (iii) az antibiotikum aktív eltávolítása a baktériumsejtből (például proton pumpa, efflux), és (iv) az aminoglikozidok támadáspontján, a riboszómális 30S-alegység fehérjéjén bekövetkezett mutáció. Az aminoglikozidok, mint régóta használt antibiotikumok, általános tulajdonságait és a velük szemben kialakult leggyakoribb rezisztenciamechanizmusokat foglalom össze néhány klinikailag fontos baktériumtörzs vonatkozásában. A multirezisztens fajok kialakulása és fékezhetetlen terjedése és a magas dózis miatti toxikus hatás elkerülése érdekében a kutatók figyelmét különböző, rezisztens baktériumokkal szembeni újabb hatásos, de kevésbé toxikus aminoglikozidok vagy azokhoz hasonló antibakteriális vegyületek fejlesztésére kell irányítani, koncentrálva a kémiai módosításokra és az aminoglikozid-módosító enzimek gátlóira.
Advisors/Committee Members: Megyeri, Attila (advisor).
Subjects/Keywords: rezisztencia;
aminoglikozid;
drug resistance;
aminoglycoside
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Géczy, K. . (2013). Aminoglikozidokkal szembeni rezisztenciamechanizmusok baktériumokban
. (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/177289
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):
Géczy, Katalin Éva. “Aminoglikozidokkal szembeni rezisztenciamechanizmusok baktériumokban
.” 2013. Thesis, University of Debrecen. Accessed March 04, 2021.
http://hdl.handle.net/2437/177289.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Géczy, Katalin Éva. “Aminoglikozidokkal szembeni rezisztenciamechanizmusok baktériumokban
.” 2013. Web. 04 Mar 2021.
Vancouver:
Géczy K. Aminoglikozidokkal szembeni rezisztenciamechanizmusok baktériumokban
. [Internet] [Thesis]. University of Debrecen; 2013. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2437/177289.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Géczy K. Aminoglikozidokkal szembeni rezisztenciamechanizmusok baktériumokban
. [Thesis]. University of Debrecen; 2013. Available from: http://hdl.handle.net/2437/177289
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cambridge
17.
Lee, Liam Changwoo.
Functional identification of molecular oncotargets associated with the resistance to ALK inhibition in neuroblastoma via genome-wide CRISPR-Cas9 screens.
Degree: PhD, 2017, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/267921
► Recent whole-exome sequencing studies of hundreds of high-risk neuroblastoma (hNB) patients have identified Anaplastic Lymphoma Kinase (ALK) as the only directly ‘druggable’ target with a…
(more)
▼ Recent whole-exome sequencing studies of hundreds of high-risk neuroblastoma (hNB) patients have identified Anaplastic Lymphoma Kinase (ALK) as the only directly ‘druggable’ target with a significant mutation rate (9%). ALK is a receptor tyrosine kinase whose dysregulation has been implicated as the driver lesion in a variety of cancer types, including Non-Small Cell Lung Cancer (NSCLC) and various paediatric malignancies. As a kinase normally only expressed during early development in the foetal brain, ALK is an ideal therapeutic target and it has proven relatively simple to target therapeutically. However, resistance to ALK-targeted therapy, particularly in ALK+ NSCLC patients has frequently been observed.
The majority of the acquired resistance mechanisms noted in NSCLC patients rely on bypass signalling pathways, which are tissue-context dependent. To proactively identify and develop strategies to counter these varied yet expected resistance mechanisms in other ALK-driven tumours, we must gain a better insight of the bypass-track mechanism(s) in a tumour-specific manner. The present study aimed to functionally identify putative resistance mechanisms against ALK inhibitors via extensive CRISPR/Cas9-based genome-wide knockout (GeCKO) or overexpression screens (SAM) in the human neuroblastoma cell line, SHSY-5Y, to develop novel therapeutic strategies for ALK mutant NBs.
The GeCKO screen identified a total of 39 genes and miRNAs, and the SAM overexpression screen identified 25 genes that induce resistance to ALK inhibitors. These putative resistance-inducing candidates were then aligned with a publicly available expression dataset of hNB patients (n = 476) to identify those with prognostic significance (Kaplan-Meier event-free survival analysis), specifically those that are indicative of relapse risk. Furthermore, all candidates identified from the screen were individually validated in vitro. Two of the candidates, one from each of the knockout and overexpression screens, were further investigated.
Inhibition of hsa-miR-1304-5p, identified from GeCKO screen, induced resistance to ALK inhibitors. Interestingly, interference of has-miR-1304-5p, in the absence of ALK inhibitors, also enabled enhanced cell viability whilst the transfection of its mimic led to a significant reduction of viability across 17 distinct NB cell lines. Through genome-wide cDNA microarrays, in silico predictions, and UTR-luciferase assays, this study identified hsa-miR-1304-5p to be a major regulator of the Ras/MAP Kinase pathway.
Overexpression of PIM1, identified from the SAM screen, in NB cell lines induced resistance to ALK inhibitors and this phenotype could be reversed on transducing cells with RNAi against PIM1. Interestingly, inhibition of PIM1 in wild-type cell lines via RNAi or pharmacological compounds led to substantially enhanced potency of ALK inhibitors suggesting PIM1 inhibitors as combinatorial agents with ALK inhibitors for the therapy of treatment-naive hNB. Through protein analysis of all identified…
Subjects/Keywords: CRISPR; ALK; Drug-resistance; Neuroblastoma
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, L. C. (2017). Functional identification of molecular oncotargets associated with the resistance to ALK inhibition in neuroblastoma via genome-wide CRISPR-Cas9 screens. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/267921
Chicago Manual of Style (16th Edition):
Lee, Liam Changwoo. “Functional identification of molecular oncotargets associated with the resistance to ALK inhibition in neuroblastoma via genome-wide CRISPR-Cas9 screens.” 2017. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021.
https://www.repository.cam.ac.uk/handle/1810/267921.
MLA Handbook (7th Edition):
Lee, Liam Changwoo. “Functional identification of molecular oncotargets associated with the resistance to ALK inhibition in neuroblastoma via genome-wide CRISPR-Cas9 screens.” 2017. Web. 04 Mar 2021.
Vancouver:
Lee LC. Functional identification of molecular oncotargets associated with the resistance to ALK inhibition in neuroblastoma via genome-wide CRISPR-Cas9 screens. [Internet] [Doctoral dissertation]. University of Cambridge; 2017. [cited 2021 Mar 04].
Available from: https://www.repository.cam.ac.uk/handle/1810/267921.
Council of Science Editors:
Lee LC. Functional identification of molecular oncotargets associated with the resistance to ALK inhibition in neuroblastoma via genome-wide CRISPR-Cas9 screens. [Doctoral Dissertation]. University of Cambridge; 2017. Available from: https://www.repository.cam.ac.uk/handle/1810/267921

University of Cambridge
18.
Cassidy, John.
Studying the Clonal Origins of Drug Resistance in Human Breast Cancers.
Degree: PhD, 2019, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/290759
► Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed,…
(more)
▼ Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market has risen substantially in the last several decades, fuelled partly by lack of efficacy in late phase clinical trials. Even in cases where a new agent is deemed 'successful', the development of resistance is often seen as inevitable and clinical responses can be fleeting. Typically, resistance to targeted therapies is thought to arise from pre-existing populations within the tumour, rather than from de novo evolution, yet few studies have experimentally tested this understanding. Indeed, recent reports in the literature have described epigenetically regulated drug tolerant populations within cancers, defined by cell-cycle regulation and/or quiescent repopulation dynamics, drug induced chromatin remodelling or differential transcription factor binding, that can be transient or permanent in nature. This thesis will outline experiments using high complexity molecular barcodes to trace the fate of individual cellular clones in the development of drug resistance. With this technique, cellular clones can be uncoupled from their genomic backgrounds, giving a new depth to our understanding of clonal selection in cancer. In particular, high complexity barcodes are used to identify a pre-existing tamoxifen resistant population in the MCF7 cell line. This resistance phenotype is then linked to the induction of embryonic transcription factor OCT4. Finally, we use our molecular barcoding technique to interrogate the repopulation dynamics of a breast cancer PDX model, supporting their use as complex model systems suitable for studying the origins and consequences of tumour heterogeneity.
Subjects/Keywords: Cancer; drug resistance; clonal tracing
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cassidy, J. (2019). Studying the Clonal Origins of Drug Resistance in Human Breast Cancers. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/290759
Chicago Manual of Style (16th Edition):
Cassidy, John. “Studying the Clonal Origins of Drug Resistance in Human Breast Cancers.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021.
https://www.repository.cam.ac.uk/handle/1810/290759.
MLA Handbook (7th Edition):
Cassidy, John. “Studying the Clonal Origins of Drug Resistance in Human Breast Cancers.” 2019. Web. 04 Mar 2021.
Vancouver:
Cassidy J. Studying the Clonal Origins of Drug Resistance in Human Breast Cancers. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 04].
Available from: https://www.repository.cam.ac.uk/handle/1810/290759.
Council of Science Editors:
Cassidy J. Studying the Clonal Origins of Drug Resistance in Human Breast Cancers. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/290759

University of Cambridge
19.
Bartlett, Sean.
Synthesis and antibacterial evaluation of diverse small molecules.
Degree: PhD, 2017, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/270198
► Hospital-acquired infections are the most frequent adverse event in healthcare delivery worldwide. Seven in ten hospital-acquired infections exhibit resistance to at least one antibiotic, and…
(more)
▼ Hospital-acquired infections are the most frequent adverse event in healthcare delivery worldwide. Seven in ten hospital-acquired infections exhibit resistance to at least one antibiotic, and three in five doctors have encountered an infection unresponsive to any treatment at all. This prolongs hospitalisation, increases suffering, and causes long-term disability and unnecessary death. At present the antibiotic pipeline is unable to meet the demand for novel antibiotics needed to treat these infections. Herein I discuss how the lack of new scaffolds, limitations of target-based screening, and poor target validation each contribute to the current bottleneck in the antibiotic pipeline. In turn, I argue that the development and application of chemical probes is a more fruitful way to make progress towards new antibiotics with novel mechanisms of action. This dissertation describes a combined chemical-biology study in the search for novel inhibitors of the human pathogens Pseudomonas aeruginosa and Staphylococcus aureus. First we extend organocatalysis to the field of diversity-oriented synthesis as a powerful means to generate molecular diversity and complexity in small molecule screening collections. We then study a family of potential biofilm inhibitors identified from a diverse screening collection, and for which we suggest a possible mode of action upon the quorum sensing receptors LasR and RhlR. Thereafter we provide evidence that a novel macrocycle, based upon the cylindrocyclophane family of natural products, inhibits methicillin-resistant S. aureus through action upon the respiratory chain. Finally, we also report insights into the structure and small molecule inhibition of a key P. aeruginosa drug target, malate synthase G. Together the findings in this dissertation encourage the development and application of divergent synthesis and unbiased screening methods in antibacterial discovery.
Subjects/Keywords: antibiotics; drug resistance; synthesis
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bartlett, S. (2017). Synthesis and antibacterial evaluation of diverse small molecules. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/270198
Chicago Manual of Style (16th Edition):
Bartlett, Sean. “Synthesis and antibacterial evaluation of diverse small molecules.” 2017. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021.
https://www.repository.cam.ac.uk/handle/1810/270198.
MLA Handbook (7th Edition):
Bartlett, Sean. “Synthesis and antibacterial evaluation of diverse small molecules.” 2017. Web. 04 Mar 2021.
Vancouver:
Bartlett S. Synthesis and antibacterial evaluation of diverse small molecules. [Internet] [Doctoral dissertation]. University of Cambridge; 2017. [cited 2021 Mar 04].
Available from: https://www.repository.cam.ac.uk/handle/1810/270198.
Council of Science Editors:
Bartlett S. Synthesis and antibacterial evaluation of diverse small molecules. [Doctoral Dissertation]. University of Cambridge; 2017. Available from: https://www.repository.cam.ac.uk/handle/1810/270198

Columbia University
20.
Tzoneva, Gannie Valentinova.
The role of cytosolic 5'-nucleotidase II (NT5C2) in drug resistance and relapse of acute lymphoblastic leukemia.
Degree: 2016, Columbia University
URL: https://doi.org/10.7916/D85Q4W77
► Acute lymphoblastic leukemia (ALL) is an aggressive hematological cancer which arises from the malignant transformation of B-cell or T-cell progenitors. Despite recent pioneering improvements in…
(more)
▼ Acute lymphoblastic leukemia (ALL) is an aggressive hematological cancer which arises from the malignant transformation of B-cell or T-cell progenitors. Despite recent pioneering improvements in intensified combination chemotherapy, 20% of pediatric and 50% of adult ALL patients present with primary drug-resistant leukemia or develop relapse. Treatment of refractory and relapsed ALL has remained a significant clinical challenge with survival rates following relapse of only 40%, highlighting the need to understand the mechanisms which drive drug resistance and relapse of ALL.
Through extensive sequencing analyses of matched diagnostic, remission and relapsed DNA samples from patients with B-precursor ALL (B-ALL) and T-cell ALL (T-ALL) we have identified recurrent relapse-specific gain-of-function mutations in the cytosolic 5'-nucleotidase II (NT5C2) gene in 25% of relapsed T-ALLs and 6% of relapsed B-ALLs. NT5C2 is a highly conserved, ubiquitously expressed enzyme which regulates intracellular purine nucleotide levels by dephosphorylating purine monophosphates. NT5C2 also dephosphorylates key metabolites in the activation of purine analog prodrugs such as 6-mercaptopurine and 6-thioguanine which are routinely used in the treatment of ALL, allowing purine analog nucleosides to be readily exported out of the cell.
Here we show that mutant NT5C2 proteins have increased 5’-nucleotidase activity and confer resistance to 6-mercaptopurine and 6-thioguanine chemotherapy when expressed in leukemic cells. Consistently, NT5C2 mutations correlate with early relapse and relapse while under therapy. We present a novel T-ALL conditional inducible knock-in mouse model of the highly recurrent NT5C2 R367Q mutation and show that expression of one Nt5c2 R367Q allele from the endogenous locus in primary T-ALL lymphoblasts induces overt resistance and disease progression under therapy with 6-mercaptopurine in vivo, while surprisingly conferring reduced growth and decreased leukemia initiating activity in the absence of chemotherapy. Metabolically we show that the observed loss of fitness in Nt5c2 R367Q tumors can be explained by a severe depletion of endogenous purine monophosphate metabolites as a result of increased Nt5c2 5’-nucleotidase activity. Consistently, using ultra-sensitive mutation analyses we show that relapse-associated NT5C2 mutations are not detectable at initial disease presentation, indicating that NT5C2-mutant tumor cells are negatively selected by clonal competition in the early stages of disease development and only positively selected under prolonged 6-mercaptopruine chemotherapy which is the backbone treatment for ALL following remission. Our findings present the first known example of chemotherapy resistance and disease progression driven by a tumor clone with decreased leukemia initiating activity, highlighting the intense selective pressure of chemotherapy in the clonal evolution of tumors from diagnosis to relapse.
Through extensive biochemical and structural characterizations of recombinant…
Subjects/Keywords: Drug resistance; Lymphoblastic leukemia; Oncology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tzoneva, G. V. (2016). The role of cytosolic 5'-nucleotidase II (NT5C2) in drug resistance and relapse of acute lymphoblastic leukemia. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D85Q4W77
Chicago Manual of Style (16th Edition):
Tzoneva, Gannie Valentinova. “The role of cytosolic 5'-nucleotidase II (NT5C2) in drug resistance and relapse of acute lymphoblastic leukemia.” 2016. Doctoral Dissertation, Columbia University. Accessed March 04, 2021.
https://doi.org/10.7916/D85Q4W77.
MLA Handbook (7th Edition):
Tzoneva, Gannie Valentinova. “The role of cytosolic 5'-nucleotidase II (NT5C2) in drug resistance and relapse of acute lymphoblastic leukemia.” 2016. Web. 04 Mar 2021.
Vancouver:
Tzoneva GV. The role of cytosolic 5'-nucleotidase II (NT5C2) in drug resistance and relapse of acute lymphoblastic leukemia. [Internet] [Doctoral dissertation]. Columbia University; 2016. [cited 2021 Mar 04].
Available from: https://doi.org/10.7916/D85Q4W77.
Council of Science Editors:
Tzoneva GV. The role of cytosolic 5'-nucleotidase II (NT5C2) in drug resistance and relapse of acute lymphoblastic leukemia. [Doctoral Dissertation]. Columbia University; 2016. Available from: https://doi.org/10.7916/D85Q4W77

University of Illinois – Chicago
21.
Logan, Latania K.
Resistance Determinants and Factors associated with Multi-drug Resistant Enterobacteriaceae in Children.
Degree: 2017, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/22220
► Background: National studies have found an increase in multi-drug resistant (MDR) Enterobacteriaceae (Ent) infections in children over the last decade; however, there is a paucity…
(more)
▼ Background: National studies have found an increase in multi-
drug resistant (MDR) Enterobacteriaceae (Ent) infections in children over the last decade; however, there is a paucity of literature on the antibiotic
resistance determinants associated with these increases, and, regarding the children most impacted by these dangerous pathogens.
Objectives: 1) To determine the genetic basis of extended-spectrum beta-lactam (ESBL), carbapenem, and fluoroquinolone
resistance (FQR) phenotypes in Enterobacteriaceae isolates from children cared for by multiple centers in the Chicago area; 2) To identify which exposures and host factors serve as predictors of infection within dominant genotypes of resistant Enterobacteriaceae recovered from children from multiple centers.
Methods: Objective 1: A retrospective cohort study of 276 GNB isolates from unique patients, phenotypically identified as beta-lactamases producers, was performed. Isolates from 5 Chicago hospitals were recovered from children ages 0-18 years hospitalized between 2011- 2015. DNA microarray (Check-Points™) was used to query the genetic background associated with beta-lactam
resistance. Determinants of quinolone
resistance (e.g., QRDR and PMFQR) were investigated. Objective 2: A case-control study of children cared for by 3 Chicago area hospitals during 2011-14 was performed. Cases were 53 children diagnosed with PMFQR containing beta-lactam resistant isolates. Controls were 131 children with antibiotic susceptible Ent infections matched by hospital, age and source. Demographics; comorbidities; device, antibiotic, and healthcare exposures; and the impact of location of patient residence were evaluated. Race categories were white, black, Hispanic, and other. Multivariable logistic regression was used to explore associations between predictors and PMFQR infection. Data were analyzed in SAS 9.4.
Results: Median age was 4.8 years, 59% were female, and 46% were outpatients. Most isolates (69%) were from urine. E. coli (62%) was most frequently recovered; and of 272 bla genes detected, the most common was blaCTX-M-1 (49%); 1.9% were CRE (4- blaKPC and 1- blaIMP-13). PMFQR was found in 56/82 (66%) and associated with QRDR mutations in 84% of cases. Overall, pAmpC were found in 12% (34/276). The blaKPC harboring K. pneumoniae were mainly non-ST258 strains, which differs from adults.
Children with PMFQR Ent infections were more likely to be diagnosed in an outpatient clinic (OR 33.1; CI 7.1, 154.7) and of race “other” (OR 6.5; CI 1.9, 22.2). Residents of Southwest Chicago were 5 times more likely to have a PMFQR Ent infection than those residing in other regions (OR 5.3; CI 1.8, 15.2); while residence in Central Chicago was associated with a 97% decreased risk (OR 0.03; CI 0.002, 0.3). Significant differences in other demographics; comorbidities; invasive devices; antibiotic use; or recent healthcare were not found.
Conclusions: Complex bla genotypes were responsible for the beta-lactam resistant phenotypes in children. Transmissible plasmid mediated
resistance may be…
Advisors/Committee Members: Hershow, Ronald (advisor), Argos, Maria (committee member), Konda, Sreenu (committee member), Hershow, Ronald (chair).
Subjects/Keywords: Children; Microbial Drug Resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Logan, L. K. (2017). Resistance Determinants and Factors associated with Multi-drug Resistant Enterobacteriaceae in Children. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22220
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):
Logan, Latania K. “Resistance Determinants and Factors associated with Multi-drug Resistant Enterobacteriaceae in Children.” 2017. Thesis, University of Illinois – Chicago. Accessed March 04, 2021.
http://hdl.handle.net/10027/22220.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Logan, Latania K. “Resistance Determinants and Factors associated with Multi-drug Resistant Enterobacteriaceae in Children.” 2017. Web. 04 Mar 2021.
Vancouver:
Logan LK. Resistance Determinants and Factors associated with Multi-drug Resistant Enterobacteriaceae in Children. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10027/22220.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Logan LK. Resistance Determinants and Factors associated with Multi-drug Resistant Enterobacteriaceae in Children. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22220
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
22.
LOWRY, MICHELLE.
Investigating mechanisms of anti-cancer drug resistance in breast cancer cells and extracellular vesicles.
Degree: School of Pharmacy & Pharma. Sciences. Discipline of Pharmacy, 2019, Trinity College Dublin
URL: http://hdl.handle.net/2262/86081
► Breast cancer is the most common female cancer diagnosed worldwide. In 2018 alone, there were over 2 million new breast cancer cases diagnosed. In Ireland,…
(more)
▼ Breast cancer is the most common female cancer diagnosed worldwide. In 2018 alone, there were over 2 million new breast cancer cases diagnosed. In Ireland, breast cancer is the most commonly diagnosed cancer in women. In Ireland, breast cancer accounts for approximately 3,141 cases each year. Of which, a subtype of breast cancer called HER2overexpressing/HER2+ breast cancer accounts for 15-25% of breast cancers. This subtype of breast cancer has a genetic mutation that causes the cancer cells to produce larger amounts of the protein called HER2. HER2 promotes the growth of cancer cells and patients with this type of breast cancer often have high levels of metastasis, or spread of the cancer to other organs. Unfortunately, like with many cancer therapies, some patients do not respond to anti-HER2 therapies, i.e. patients are or become resistant to therapy. Some patient?s tumours will immediately not respond to therapy (innate
resistance), whereas, other patient tumour?s will initially respond well to the therapies but overtime the cancer cells can find ways to overcome the effects of the therapy i.e. the tumours become resistant to therapy (adaptive
resistance). Innate and adaptive
resistance to anticancer therapies are the main reasons that anti-cancer drugs fail in the clinic. It is imperative that we investigate the mechanisms of
drug resistance, find ways to overcome this
resistance and find ways to predict and/or find predictive biomarkers.
The focus of this PhD is on a
drug that stops HER2 working, it is called Neratinib. Neratinib prevents HER2 functioning and in doing so it can prevent cancer cell growth. Neratinib was approved by the Food and
Drug Administration (FDA) in July 2017. Neratinib is showing promise in the clinic but, like most therapies, the issue of
resistance prevails. We have developed HER2+ breast cancer cell lines that are resistant to neratinib i.e. neratinib does not kill them. When we compared cells that die from neratinib with cells that do not die after neratinib treatment, we found that the resistant cell lines produce very large amounts of a protein called PROTEIN X. The cells that are sensitive to neratinib or the cells that die after neratinib treatment, do not produce large amounts of PROTEIN X. We believe that PROTEIN X acts like a defence system for breast cancer cells.
This discoveries made in this PhD may be imperative to overcoming neratinib
resistance in the future, for predicting response to therapy (so that patients can be stratified into those who are likely versus unlikely to respond to HER-targeting), and so improving the survival rates of patients treated with neratinib and other HER2-targeted therapies. We also believe that PROTEIN X has potential as a predictive biomarker for HER2 therapies such as lapatinib and trastuzumab, but most notably for neratinib. PROTEIN X may be an important marker for future therapeutic decisions in clinics.
Advisors/Committee Members: O'Driscoll, Lorraine.
Subjects/Keywords: Breast cancer; Cancer drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
LOWRY, M. (2019). Investigating mechanisms of anti-cancer drug resistance in breast cancer cells and extracellular vesicles. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/86081
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):
LOWRY, MICHELLE. “Investigating mechanisms of anti-cancer drug resistance in breast cancer cells and extracellular vesicles.” 2019. Thesis, Trinity College Dublin. Accessed March 04, 2021.
http://hdl.handle.net/2262/86081.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
LOWRY, MICHELLE. “Investigating mechanisms of anti-cancer drug resistance in breast cancer cells and extracellular vesicles.” 2019. Web. 04 Mar 2021.
Vancouver:
LOWRY M. Investigating mechanisms of anti-cancer drug resistance in breast cancer cells and extracellular vesicles. [Internet] [Thesis]. Trinity College Dublin; 2019. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2262/86081.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
LOWRY M. Investigating mechanisms of anti-cancer drug resistance in breast cancer cells and extracellular vesicles. [Thesis]. Trinity College Dublin; 2019. Available from: http://hdl.handle.net/2262/86081
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cambridge
23.
Cassidy, John.
Studying the clonal origins of drug resistance in human breast cancers.
Degree: PhD, 2019, University of Cambridge
URL: https://doi.org/10.17863/CAM.37959
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774632
► Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed,…
(more)
▼ Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market has risen substantially in the last several decades, fuelled partly by lack of efficacy in late phase clinical trials. Even in cases where a new agent is deemed 'successful', the development of resistance is often seen as inevitable and clinical responses can be fleeting. Typically, resistance to targeted therapies is thought to arise from pre-existing populations within the tumour, rather than from de novo evolution, yet few studies have experimentally tested this understanding. Indeed, recent reports in the literature have described epigenetically regulated drug tolerant populations within cancers, defined by cell-cycle regulation and/or quiescent repopulation dynamics, drug induced chromatin remodelling or differential transcription factor binding, that can be transient or permanent in nature. This thesis will outline experiments using high complexity molecular barcodes to trace the fate of individual cellular clones in the development of drug resistance. With this technique, cellular clones can be uncoupled from their genomic backgrounds, giving a new depth to our understanding of clonal selection in cancer. In particular, high complexity barcodes are used to identify a pre-existing tamoxifen resistant population in the MCF7 cell line. This resistance phenotype is then linked to the induction of embryonic transcription factor OCT4. Finally, we use our molecular barcoding technique to interrogate the repopulation dynamics of a breast cancer PDX model, supporting their use as complex model systems suitable for studying the origins and consequences of tumour heterogeneity.
Subjects/Keywords: Cancer; drug resistance; clonal tracing
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cassidy, J. (2019). Studying the clonal origins of drug resistance in human breast cancers. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.37959 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774632
Chicago Manual of Style (16th Edition):
Cassidy, John. “Studying the clonal origins of drug resistance in human breast cancers.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021.
https://doi.org/10.17863/CAM.37959 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774632.
MLA Handbook (7th Edition):
Cassidy, John. “Studying the clonal origins of drug resistance in human breast cancers.” 2019. Web. 04 Mar 2021.
Vancouver:
Cassidy J. Studying the clonal origins of drug resistance in human breast cancers. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 04].
Available from: https://doi.org/10.17863/CAM.37959 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774632.
Council of Science Editors:
Cassidy J. Studying the clonal origins of drug resistance in human breast cancers. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.37959 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774632

University of New South Wales
24.
Jiamsakul, Awachana.
HIV Drug Resistance and Adherence to Antiretroviral Therapy in Asia.
Degree: Kirby Institute, 2015, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/55477
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37799/SOURCE01?view=true
► The expansion of combination antiretroviral therapy (cART) in resource-limited settings has led to improved survival but also the emergence of HIV drug resistance associated mutations…
(more)
▼ The expansion of combination antiretroviral therapy (cART) in resource-limited settings has led to improved survival but also the emergence of HIV
drug resistance associated mutations (RAMs). As treatment strategies lean towards earlier cART initiation, it is expected that an increasing number of HIV-infected individuals will be exposed to cART for longer, potentially leading to higher prevalence of RAMs in both treatment naive, through transmitted RAMs, and treatment experienced individuals. This thesis aims to evaluate RAMs in recently infected individuals and those who have failed first-line cART in Asia. Additionally, adherence to cART, an important predictor of RAMs, was also investigated.Analysis datasets were obtained from the TREAT Asia HIV databases. Firstly, the applications of different types of
resistance interpretation systems on HIV-1 CRF01_AE were compared. Proportions of RAMs in recently-infected and treatment experienced individuals were then analysed, and the corresponding second-line virological outcome adjusting for adherence and genotypic susceptibility score were determined. Levels of suboptimal adherence utilising the self-reported questionnaire were evaluated. Additionally, the effects of unplanned treatment interruptions on treatment outcomes after cART resumption were investigated. Although developed from subtype B, genotypic and virtual phenotypic
resistance interpretation systems proved to be reliable in their predicted
resistance calls for non-B subtypes, particularly CRF01_AE. RAMs in recently infected individuals were below 15%, however, multi-
drug RAMs found in patients failing first-line cART existed in a high proportion but were not associated with second-line virological suppression. Adherence was the only factor showing a significant association, conferring the importance of high-level adherence beyond first-line therapy. Sites that assessed adherence more frequently, and longer time on cART, were associated with better adherence. Treatment interruptions due to adverse events did not have an effect on treatment response after cART had been resumed, possibly due to the shorter duration. Longer time off treatment was associated with higher hazard of treatment failure.Continued monitoring of RAMs in recently infected and treatment experienced individuals in Asia should be encouraged. Greater emphasis on adherence counselling at the early stages of cART is beneficial in promoting treatment and program retention.
Advisors/Committee Members: Law, Matthew, Kirby Institute, Faculty of Medicine, UNSW, Kerr, Stephen, HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand;, Sungkanuparp, Somnuek, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;.
Subjects/Keywords: Adherence; HIV; Drug resistance; Asia
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jiamsakul, A. (2015). HIV Drug Resistance and Adherence to Antiretroviral Therapy in Asia. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/55477 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37799/SOURCE01?view=true
Chicago Manual of Style (16th Edition):
Jiamsakul, Awachana. “HIV Drug Resistance and Adherence to Antiretroviral Therapy in Asia.” 2015. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021.
http://handle.unsw.edu.au/1959.4/55477 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37799/SOURCE01?view=true.
MLA Handbook (7th Edition):
Jiamsakul, Awachana. “HIV Drug Resistance and Adherence to Antiretroviral Therapy in Asia.” 2015. Web. 04 Mar 2021.
Vancouver:
Jiamsakul A. HIV Drug Resistance and Adherence to Antiretroviral Therapy in Asia. [Internet] [Doctoral dissertation]. University of New South Wales; 2015. [cited 2021 Mar 04].
Available from: http://handle.unsw.edu.au/1959.4/55477 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37799/SOURCE01?view=true.
Council of Science Editors:
Jiamsakul A. HIV Drug Resistance and Adherence to Antiretroviral Therapy in Asia. [Doctoral Dissertation]. University of New South Wales; 2015. Available from: http://handle.unsw.edu.au/1959.4/55477 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37799/SOURCE01?view=true

Texas State University – San Marcos
25.
Quintanilla, Vicente Carlos.
Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio.
Degree: Masters of Science, Biology, 2012, Texas State University – San Marcos
URL: https://digital.library.txstate.edu/handle/10877/12388
► The neural retina of zebrafish (Danio rerio) is one of the more specialized tissues of the diencephalon, and it encompasses distinct and well defined cellular…
(more)
▼ The neural retina of zebrafish (Danio rerio) is one of the more specialized tissues of the diencephalon, and it encompasses distinct and well defined cellular classes, which includes the photoreceptor cells. The retinal pigment epithelium (RPE) forms the distal blood-retinal barrier playing essential functions for cellular homeostasis. The zebrafish is a powerful model for functional retinal studies as it closely resembles the retina of higher vertebrates. Nonetheless, the zebrafish retina exhibits distinct mechanisms for light- and dark-adaptation termed retinomotor movements. These mechanisms for light- and dark-adaptation occur by morphological changes of photoreceptors along with redistribution of melanosomes within the apical processes of RPE cells. The purpose of retinomotor movements is to protect and optimally expose cones or rods to light quanta. Regulation of retinomotor movements involves cAMP as higher concentration of cAMP induces the dark-adaptive response. The multidrug
resistance protein 4 (Mrp4) is the member of the Mrp family with the highest affinity for cAMP. The aim of this study is to characterize the spatial and temporal patterns of expression of Mrp4 in the retina to elucidate the role of Mrp4 in regulating retinomotor movements. In this study, I show Mrp4 expression on dark-and light-adapted retinas, and I report subcellular location and distribution of Mrp4.1 also show that Mrp4 inhibition results in decreased melanosome aggregation. The results from this study are consistent with the model I propose, in which Mrp4 regulates intracellular cAMP levels by exporting cAMP into the subretinal space as cytoplasmic levels rise under dark conditions. Once in the subretinal space, cAMP is taken up by RPE to induce and maintain the dark-adapted state.
Advisors/Committee Members: Garcia, Dana (advisor).
Subjects/Keywords: Androgens; Zebra danio; Drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Quintanilla, V. C. (2012). Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio. (Masters Thesis). Texas State University – San Marcos. Retrieved from https://digital.library.txstate.edu/handle/10877/12388
Chicago Manual of Style (16th Edition):
Quintanilla, Vicente Carlos. “Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio.” 2012. Masters Thesis, Texas State University – San Marcos. Accessed March 04, 2021.
https://digital.library.txstate.edu/handle/10877/12388.
MLA Handbook (7th Edition):
Quintanilla, Vicente Carlos. “Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio.” 2012. Web. 04 Mar 2021.
Vancouver:
Quintanilla VC. Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio. [Internet] [Masters thesis]. Texas State University – San Marcos; 2012. [cited 2021 Mar 04].
Available from: https://digital.library.txstate.edu/handle/10877/12388.
Council of Science Editors:
Quintanilla VC. Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio. [Masters Thesis]. Texas State University – San Marcos; 2012. Available from: https://digital.library.txstate.edu/handle/10877/12388

Rutgers University
26.
Blankson, Gifty Ayensu, 1986-.
Structure-activity studies on bacterial efflux inhibitors.
Degree: PhD, Medicinal Chemistry, 2016, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/49914/
► Antibiotic resistance poses a significant challenge in anti-infective therapy. There are several mechanisms involved in antibiotic resistance with efflux being a major determinant. Overcoming efflux…
(more)
▼ Antibiotic resistance poses a significant challenge in anti-infective therapy. There are several mechanisms involved in antibiotic resistance with efflux being a major determinant. Overcoming efflux will allow for the reintroduction of old antibiotics and prevent the development of resistance to new antibiotics. Several bacterial efflux pump inhibitors (EPIs) have been discovered, but none of these compounds have been FDA-approved for use in humans. There is a need for a systematic study of some of these inhibitors to gain a better understanding of their structure activity relationship (SAR). This work focuses on the SAR studies conducted on two classes of known EPI inhibitors. Analogues of aryl piperazines (biphenyl piperazines and naphthalene amines) were synthesized and tested for their EPI activity. None of the compounds in this series exhibited EPI activity and thus no further exploration was done on their SAR. Structurally simpler analogues of phenylalanine-arginine β-naphthylamide (PAβN) were also designed and an SAR study conducted on the three different scaffolds proposed. The three scaffolds include the “normal” amides, the “reverse” amides and the secondary amine series. Although these scaffolds exhibited some similarities in their SAR, there were some differences. In all cases, the 1,5-diphenylpentane core was the preferred substituent on the right hand side of the molecules. For the left hand side, diaminopentane was the preferred substituent. Further studies revealed that N5 substitution was detrimental to EPI activity. The “reverse” amides had better activity when compared against their analogous “normal” amides. The data indicated that a bis-alkylaryl was necessary for activity and that there was preference for the aryl to be hydrophobic. A methylene insertion in the reverse amides series gave a compound that caused 512-fold reduction in the minimum inhibitory concentration (MIC) of clarithromycin (PAβN, the historical EPI standard offered a 4-fold reduction in MIC). The amine analogues also offered some active compounds with one of these compounds causing a 128-fold reduction in the MIC of clarithromycin. (These tests were done in E. coli). Some success was achieved in P. aeruginosa; two compounds when independently co-administered with levofloxacin resulted in a 32-fold decrease in the MIC of levofloxacin.
Advisors/Committee Members: LaVoie, Edmond J (chair), Rice, Joseph E (internal member), Hu, Longqin (internal member), Pilch, Daniel S (outside member).
Subjects/Keywords: Drug resistance in microorganisms; Antibiotics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Blankson, Gifty Ayensu, 1. (2016). Structure-activity studies on bacterial efflux inhibitors. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/49914/
Chicago Manual of Style (16th Edition):
Blankson, Gifty Ayensu, 1986-. “Structure-activity studies on bacterial efflux inhibitors.” 2016. Doctoral Dissertation, Rutgers University. Accessed March 04, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/49914/.
MLA Handbook (7th Edition):
Blankson, Gifty Ayensu, 1986-. “Structure-activity studies on bacterial efflux inhibitors.” 2016. Web. 04 Mar 2021.
Vancouver:
Blankson, Gifty Ayensu 1. Structure-activity studies on bacterial efflux inhibitors. [Internet] [Doctoral dissertation]. Rutgers University; 2016. [cited 2021 Mar 04].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49914/.
Council of Science Editors:
Blankson, Gifty Ayensu 1. Structure-activity studies on bacterial efflux inhibitors. [Doctoral Dissertation]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49914/

Rutgers University
27.
Varghese, Nevin.
Characterization of the interaction of daptomycin with bacterial liposomal analogues.
Degree: MS, Biomedical Engineering, 2016, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/51486/
► Efforts to curb the prevalence of antibiotic resistant bacteria are unable to keep up with the aggressive adaptation of these bacterial species to existing antibiotics.…
(more)
▼ Efforts to curb the prevalence of antibiotic resistant bacteria are unable to keep up with the aggressive adaptation of these bacterial species to existing antibiotics. Therefore, examining the interaction of existing antibiotics with bacteria may reveal previously unknown bacterial susceptibilities. Daptomycin is a typical second-line treatment for antibiotic-resistant gram positive bacterial strains, like methicillin-resistant Staphylococcus aureus (MRSA). Its proposed mechanism of action is to bind to the negatively charged phosphatidyglycerol (PG) head groups of the bacterial cytoplasmic membrane via a calcium ion dependent process. However, the specific mechanisms by which daptomycin exerts its bacteriocidality are currently unknown. It has been hypothesized that bacterial membrane rigidity may have an effect on susceptibility to daptomycin. Additionally, there is evidence to suggest that the charge of the bacterial membrane charge affects daptomycin's mechanism of action. Our study aims to systematically analyze the interaction of daptomycin with liposomal bacterial analogues by varying the rigidity and the zeta potential of the liposomes. Our results show possible mechanisms for targeting daptomycin
resistance in gram positive bacteria.
Advisors/Committee Members: Sofou, Stavroula (chair), Pierce, Mark (internal member), Langrana, Noshir (internal member).
Subjects/Keywords: Liposomes; Drug resistance in microorganisms
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Varghese, N. (2016). Characterization of the interaction of daptomycin with bacterial liposomal analogues. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/51486/
Chicago Manual of Style (16th Edition):
Varghese, Nevin. “Characterization of the interaction of daptomycin with bacterial liposomal analogues.” 2016. Masters Thesis, Rutgers University. Accessed March 04, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/51486/.
MLA Handbook (7th Edition):
Varghese, Nevin. “Characterization of the interaction of daptomycin with bacterial liposomal analogues.” 2016. Web. 04 Mar 2021.
Vancouver:
Varghese N. Characterization of the interaction of daptomycin with bacterial liposomal analogues. [Internet] [Masters thesis]. Rutgers University; 2016. [cited 2021 Mar 04].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51486/.
Council of Science Editors:
Varghese N. Characterization of the interaction of daptomycin with bacterial liposomal analogues. [Masters Thesis]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51486/

University of Oxford
28.
Whiteley, Rosalind.
Effect of multiple antibiotic treatments on the evolution of antibiotic resistance in Pseudomonas aeruginosa.
Degree: PhD, 2014, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:ee7c9dd7-bdcf-481b-b16c-9bb7b99f5328
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711792
► To combat the ever-growing clinical burden imposed by antibiotic-resistant pathogens, multiple-antibiotic treatments are increasingly being considered as promising treatment options. The impact of multiple-antibiotic treatments…
(more)
▼ To combat the ever-growing clinical burden imposed by antibiotic-resistant pathogens, multiple-antibiotic treatments are increasingly being considered as promising treatment options. The impact of multiple-antibiotic treatments on the evolution of resistance is not well understood however, and debate is ongoing about the effectiveness of various multiple-antibiotic treatments. In this thesis, I investigate how aspects of multiple-antibiotic treatments impact the rate of evolution of antibiotic resistance in the opportunistic human pathogen Pseudomonas aeruginosa. In particular, I look at the impact of interactions between antibiotics in combination on the evolution of resistance, and how creating heterogeneity in the antibiotic environment by rotating the antibiotics used may change the rate of evolution of resistance. I characterise the interactions present in 120 combinations of antibiotics and find that the type of interaction can be predicted by the mechanism of action of the antibiotics involved. I investigate the effect of a subset of these combinations on the evolution of antibiotic resistance. My results refute the influential but poorly-evidenced hypothesis that synergistic combinations accelerate the evolution of resistance, even when synergistic combinations have the same inhibitory effect on sensitive bacteria as additive or antagonistic antibiotic combinations. I focus on a combination of the antibiotics ceftriaxone and sulfamethoxazole and test whether it is more effective in preventing the evolution of resistance than predicted by the inhibitory effect of the combination on sensitive bacteria. I do not find the combination to be more effective than predicted. Finally, I create heterogeneous antibiotic environments by rotating the antibiotic present at different rates. For the first time in a laboratory setting, I test how varying the rate of fluctuation in the antibiotics present in a heterogeneous antibiotic environment impacts the rate of evolution of resistance. Unexpectedly, I find the rate of evolution of resistance increases with increasing levels of antibiotic heterogeneity.
Subjects/Keywords: 616.9; drug interactions; drug resistance; multiple antibiotic resistance; Pseudomonas aeruginosa; antibiotic resistance; evolution; environmental heterogeneity; multi-drug resistance
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Whiteley, R. (2014). Effect of multiple antibiotic treatments on the evolution of antibiotic resistance in Pseudomonas aeruginosa. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:ee7c9dd7-bdcf-481b-b16c-9bb7b99f5328 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711792
Chicago Manual of Style (16th Edition):
Whiteley, Rosalind. “Effect of multiple antibiotic treatments on the evolution of antibiotic resistance in Pseudomonas aeruginosa.” 2014. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:ee7c9dd7-bdcf-481b-b16c-9bb7b99f5328 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711792.
MLA Handbook (7th Edition):
Whiteley, Rosalind. “Effect of multiple antibiotic treatments on the evolution of antibiotic resistance in Pseudomonas aeruginosa.” 2014. Web. 04 Mar 2021.
Vancouver:
Whiteley R. Effect of multiple antibiotic treatments on the evolution of antibiotic resistance in Pseudomonas aeruginosa. [Internet] [Doctoral dissertation]. University of Oxford; 2014. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:ee7c9dd7-bdcf-481b-b16c-9bb7b99f5328 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711792.
Council of Science Editors:
Whiteley R. Effect of multiple antibiotic treatments on the evolution of antibiotic resistance in Pseudomonas aeruginosa. [Doctoral Dissertation]. University of Oxford; 2014. Available from: http://ora.ox.ac.uk/objects/uuid:ee7c9dd7-bdcf-481b-b16c-9bb7b99f5328 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711792

University of Guelph
29.
Ward, David.
Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump.
Degree: MS, Department of Molecular and Cellular Biology, 2012, University of Guelph
URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/3309
► P-glycoprotein (Pgp, ABCB1) is a polyspecific efflux transporter implicated in multidrug resistance in human cancers. In this study, tetramethylrhodamine-5-carbonyl azide (AzTMR) was covalently crosslinked to…
(more)
▼ P-glycoprotein (Pgp, ABCB1) is a polyspecific efflux transporter implicated in multidrug
resistance in human cancers. In this study, tetramethylrhodamine-5-carbonyl azide (AzTMR) was covalently crosslinked to the Pgp
drug binding pocket with a stoichiometry of 1. The Pgp-AzTMR adduct was functionally equivalent to unlabelled Pgp and retained its ability to transport Hoechst 33342. The binding site of AzTMR in Pgp was nonpolar, with a similar environment to that of propanol. Pgp-AzTMR could bind a second
drug molecule, with a higher affinity for H-site drugs and lower affinity for other R-site drugs. Unlabelled Pgp interacted with dimeric versions of known Pgp modulators, binding them with higher affinity than the monomer. These compounds were also found to either stimulate or inhibit Pgp ATPase activity depending on the concentration. Pgp-AzTMR was able to bind dimeric drugs, indicating that 3 substrate moieties can fit into the binding pocket.
Advisors/Committee Members: Sharom, Frances J. (advisor).
Subjects/Keywords: P-glycoprotein; Pgp; drug resistance; cancer; tumour; MDR; drug binding; drug transport; multidrug resistance; chemotherapy
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ward, D. (2012). Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/3309
Chicago Manual of Style (16th Edition):
Ward, David. “Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump.” 2012. Masters Thesis, University of Guelph. Accessed March 04, 2021.
https://atrium.lib.uoguelph.ca/xmlui/handle/10214/3309.
MLA Handbook (7th Edition):
Ward, David. “Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump.” 2012. Web. 04 Mar 2021.
Vancouver:
Ward D. Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump. [Internet] [Masters thesis]. University of Guelph; 2012. [cited 2021 Mar 04].
Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/3309.
Council of Science Editors:
Ward D. Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump. [Masters Thesis]. University of Guelph; 2012. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/3309

University of Cape Town
30.
Kosmas, Petrus Ndiiluka.
Extensively drug-resistant tuberculosis in Africa: prevalence and factors associated: a systematic review and meta-analysis.
Degree: MPH, Public Health and Family Medicine, 2019, University of Cape Town
URL: http://hdl.handle.net/11427/31604
► Background: There is a dearth of information regarding prevalence of extensively drugresistant tuberculosis (XDR-TB) in Africa. Although countries in Africa conduct national tuberculosis surveys on…
(more)
▼ Background: There is a dearth of information regarding prevalence of extensively drugresistant tuberculosis (XDR-TB) in Africa. Although countries in Africa conduct national tuberculosis surveys on a regular basis, this information has not been systematically reviewed to ascertain the overall prevalence of XDR-TB in Africa. Methods: The study aimed to perform a systematic review and meta-analysis of the prevalence and factors associated with prevalence of pulmonary XDR-TB among adults in Africa. Eligible studies, published between 2006 and 2018, were sourced from various electronic databases including PubMed, Scopus, and Web of Science. Meta-analysis was performed using STATA (version 14.2) statistical software. The protocol of this review was registered with PROSPERO, reg No CRD42018117037. Result: A total of 6242 records were retrieved. Forty-eight studies were screened for eligibility and seven, which varied in terms of country setting and study design, were included. The prevalence of XDR-TB is 4% (95%CI 2-7) among participants tested for second-line anti-TB
drug resistance, and 3% (95%1-6) among participants with
drug resistant TB. The prevalence of XDR-TB was 7% (95%CI 1-18) among participants with MDR-TB. A few studies reported on the factors associated with the prevalence of XDR-TB. Discussion: The reported prevalence of XDR-TB among participants tested for second-line anti-TB
drug resistance is low compared to WHO estimates. The systematic review underscores a dearth of studies depicting the reality regarding the prevalence of XDR-TB in Africa. Policymakers and stakeholders interested in
drug-resistant TB should apply prudence when considering XDR-TB prevalence reported for Africa.
Advisors/Committee Members: Ncayiyana, Jabulani (advisor), Engel, Mark E. (advisor).
Subjects/Keywords: prevalence; tuberculosis; extensively drug-resistant tuberculosis; drug resistance; drug susceptibil
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kosmas, P. N. (2019). Extensively drug-resistant tuberculosis in Africa: prevalence and factors associated: a systematic review and meta-analysis. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/31604
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):
Kosmas, Petrus Ndiiluka. “Extensively drug-resistant tuberculosis in Africa: prevalence and factors associated: a systematic review and meta-analysis.” 2019. Thesis, University of Cape Town. Accessed March 04, 2021.
http://hdl.handle.net/11427/31604.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kosmas, Petrus Ndiiluka. “Extensively drug-resistant tuberculosis in Africa: prevalence and factors associated: a systematic review and meta-analysis.” 2019. Web. 04 Mar 2021.
Vancouver:
Kosmas PN. Extensively drug-resistant tuberculosis in Africa: prevalence and factors associated: a systematic review and meta-analysis. [Internet] [Thesis]. University of Cape Town; 2019. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/11427/31604.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kosmas PN. Extensively drug-resistant tuberculosis in Africa: prevalence and factors associated: a systematic review and meta-analysis. [Thesis]. University of Cape Town; 2019. Available from: http://hdl.handle.net/11427/31604
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
◁ [1] [2] [3] [4] [5] … [44] ▶
.