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Applying a new technique, the interferon gamma liposomal delivery system to improve drug delivery in the treatment of Lung Cancer
Alhawamdeh, Maysa F.J.
Alhawamdeh, Maysa F.J.
Publication Date
2021
End of Embargo
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
School of Chemistry & Biosciences, Faculty of Life Sciences
Awarded
2021
Embargo end date
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Abstract
Lung cancer is one of the main causes of death worldwide, with most patients
suffering from an advanced unresectable or metastatic non-small cell lung
cancer. The mortality trends are mostly related to patterns of tobacco use,
specifically from cigarettes. Tobacco is the basic etiological agent found as a
consequence of the inhalation of tobacco smoke. Published data show the use
of interferons (IFNs) in the treatment of lung tumours due to their potential in
displaying antiproliferative, anti-angiogenic, immunoregulatory, and proapoptotic
effects. Type1 IFNs have been employed as treatments for many types of cancer,
both for haematological cancers and solid tumours. The IFN-γ (naked) functions
as an anticancer agent against various forms of cancer. Hence, this study aimed
to investigate the genoprotective and genotoxic effects of IFN-γ liposome (nano)
on 42 blood samples from lung cancer patients, compared to the same sample
size from healthy individuals. The effectiveness of IFN- γ liposome against
oxidative stress was also evaluated in this study. A concentration of 100U/ml
of IFN-γ liposome was used to treat the lymphocytes in: Comet and
micronucleus assays, Comet repair, Western blotting and real-time polymerase
chain reaction (qPCR) were based on a preliminary test for the optimal dose.
The lymphocytes from lung cancer patients presented with higher DNA damage
levels than those of healthy individuals. IFN-γ liposome was not found to induce any DNA damage in the lymphocytes. Also, it caused a significant reduction in
DNA damage in the lymphocytes from lung cancer patients in; Comet, Comet
repair and micronucleus assays. Furthermore, the 100U/ml of IFN-γ liposome
significantly reduced the oxidative stress caused by H2O2 and appeared to be
effective in both groups using the Comet and micronucleus assays. Results
from; Comet, Comet repair and micronucleus assays were consistent.
The data obtained indicated that IFN-γ in both forms (naked INF-γ and INF-γ
nano-liposome) may potentially be effective for the treatment of lung cancer and
showed the ability of IFN-γ liposome to reduce the DNA damage more than the
naked form.
The IFN-γ in both forms has also shown anti-cancer potential in the lymphocytes
from lung cancer patients by regulating the expression of p53, p21, Bcl-2 at
mRNA and protein levels by up-regulating the p53 and p21 to mediate cell cycle
arrest and DNA repair in lung cancer patients.
The findings of this study are consistent with the view that the naked IFN-γ and
liposome could have a significant role in cancer treatment, including lung cancer.
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Type
Thesis
Qualification name
PhD