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Home > Identification and Modeling of Regulatory Networks and Development of Anti-Cancer Drug-Conjugated Nanoparticles for Breast Cancer Therapy

Identification and Modeling of Regulatory Networks and Development of Anti-Cancer Drug-Conjugated Nanoparticles for Breast Cancer Therapy

Thesis Info

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Author

Khalid, Sumara

Program

PhD

Institute

National University of Sciences & Technology

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Bio sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12958/1/Samra_khalid_Applied_Biosciences_HSR_2018_NUST_10.08.2018.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726389994

Similar


Breast cancer is the second leading cause of cancer-related mortalities among females worldwide. It is genetically heterogeneous disease caused by various environmental and genetic factors. Abnormal expression of various genes/proteins such as chemokine C-X-C motif (receptor 4), insulin like growth factor-1 receptor and estrogen growth factor receptor and their associated biological regulatory networks are linked with breast cancer. In this study, the crosstalk interaction between these genes/proteins and their associated signaling networks involved in breast cancer metastasis were studied by using both in-silico (qualitative modeling, hybrid PetriNet modeling, pharmacophore modeling and virtual screening) and in-vitro approaches (genotyping, cell viability assay, quantitative real time polymerase chain reaction and western blotting). The association of rs1801157 single nucleotide polymorphism, located within the C-X-C motif ligand 12 (CXCL12) gene, with the development of breast cancer was assessed. The results of genotyping showed the significant prevalence of genotype GG (p<0.05) with a number of variables including patient’s age, weight, lymph nodes status, hormonal imbalances (ER and PR) and family history using multivariable logistic regression among Pakistani breast cancer patients as compared to AA genotype. Our in-silico results suggested that rs1801157 single nucleotide polymorphism identified in CXCL12 gene has crosstalk link with insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) signaling and is an important factor in predicting the outcomes of breast cancer therapy, which can also result in multidrug resistance due to induction of insulin like growth factor-1. Furthermore, to address the problem of multidrug resistance in breast cancer cells, an effective and non-toxic biologically synthesized silver nanoparticles (drug delivery vehicles) were conjugated with anti-cancer inhibitors such as fulvestrant and gefitinib to inhibit the activity of multiple genes and proteins such as estrogen growth factor receptor, C-X-C motif (ligand 12), phosphoinositide 3 kinase, insulin receptor substrate-1, insulin like growth factor-1 receptor, PDZ domain containing 1 and estrogen receptor-α to treat breast cancer cells. In conclusion, for a multifactorial disease like breast cancer, more than one therapeutic targets should be inhibited with an effective drug delivery vehicle to induce apoptosis in cancer cells.
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آثم مرزا

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نوجوانوں میں تعلیم و تربیت کے فقدان کا تدارک اور سدباب: سیرت مبارکہ کی روشنی میں

Youth is no doubt the asset of Muslim world. If they are utilized in charitable activities; in the protection of respect and honor; and developmental works, they can prove to be beneficial and a blessing. While if they are taken by destructive elements in their hands they will become source of destruction and harm. By providing proper Islamic education, our future will be in safe hands and will breath in an air of respect among other nations. In young age, deterioration in manners and moral corruption are alarming and cause mischief in society. Therefore, the interest taken in the problems of youth will result in a progressive society and ummah. Islam has given a special place to youth and has declared them future architect and leaders of humanity. The holy prophet S.A.W has given much importance to the youth and focused on them during his life time.  In Islamic history, Muslim youth has represented the Muslim world in golden words and has spread the message of Islam’s moral height and greatness to the coming generations and nations. Due to the importance of youth problem of the youth in current time regarding lack of education and training are particularly discussed in this article. The research article begins with the detailed study of the research done in the area of education and socialization of youth. Moreover, the importance of education and socialization has been discussed in the light of the teachings of Quran and Hadith. After this, decadence in education, factors responsible for the decadence in education and its worse consequences have been thoroughly discussed in the light of the teachings of Islam.  As there are several reasons responsible for the downfall of education like: parents, teachers, education system, society, state, preachers, political parties and media, therefore, responsibility of the remedy of this lack of proper education and socialization also depend on all these stake holders. In the end of the paper, recommendations are given for the cure of decadence in education.

Establishment, Screening and Characterization of Salt Stress Tolerance in Glycine Max L.

Glycine max (L.) Merr.production is affected by a number of biotic and abiotic stresses. In order to overcome these challenges, development of transgenic plants, production of high-quality varieties and secondary metabolites, preservation of rare plants and protection of germplasms is of prime importance. In this regard, proper regeneration system for plant growth is needed to overcome dormancy and low germination issues by using appropriate growth hormones. In the proposed study, Glycine max (Variety Swat84) was assessed to investigate salt tolerance on the basis of growth, yield, physiological and biochemical responses. Seeds were germinated on MS medium with different concentrations of hormones for plantlet formation. Excellent callus was formed using 2, 4-D (2, 4-dichlorophenoxyacetic acid) at 4.0 mg L-1 concentration. Significant induction and elongation of shoot were recorded using a combination of BAP (6Benzylaminopurine) +KIN (Kinetin) at 2.0 mg L-1 + 1.0 mg L-1 respectively while maximum root induction and elongation were recorded using IBA (Indole-3-butryic acid) at 0.5 mg L-1 concentration. For the salt tolerance experiment, 0.10 g of callus was shifted to MS medium supplemented with NaCl (sodium chloride) at concentrations of 0, 50, 100, 150 and 200 mM.Callus formation showed considerable decrease at all salt concentrations as compared to control. Under saline conditions, stunted shoot growth, leaf chlorosis and defoliation occurred with increasing salt stress. The root length also decreased significantly at all salt treatments from 50 mM NaCl to 200 mM NaCl.The screening of selected clones were performed by using growth rate in term of fresh and dry weight as well as fresh and dry weight ratio of callus, shoot and root. Membrane thermo stability (EC), lipid peroxidation (MDA) and Hydrogen peroxide (H2O2) assays were performed to assess the stress induced damages. Salt stress significantly showed high electrolyte leakage of membranes and MDA contents both in callus and shoot. While, H2O2 intensity in callus showed an increase at 100 mM concentration and in shoot, an increase in H2O2 intensity was observed at 50 mM.Whereas, maximum proline was found at 100 mM NaCl concentration in both callus and shoot. Regarding total soluble protein, an increase at 200 mM concentration was observed in callus while an increase was observed at 100 mM NaCl in shoot.Furthetmore,SDS-PAGE analysis revealed that in both callus and shoot, the band intensity decreased with increasing salt stress level, but at 100 mM concentration, a 75kDa band was differentially expressed and all bands showed almost lowest level of intensity at NaCl 200 mM. From the results of present analysis, it can be concluded that salt stress has a destructive effecton the plants development, growth, physiology and yield.The intense effects of salinity can be overcome by using salt tolerant cell lines and maintain sustained growth on medium supplemented with NaCl when compared to salt sensitive cell lines. The significance of this study was to identify the optimal concentration of MS medium with growth hormones for improving the regeneration of Glycine max to reduce the period of regeneration using cotyledonary node.Transgenic crops can be developed which can be used not only for expression of different biochemical functions, but also for stress signal transduction that increase stress effects in plants. For cell protection, higher amount of proline and protein play an important role against oxidative stresses. Collectively, all these mechanisms allow plants to stay alive under extreme salt stress thereby leading to higher yield production of Glycine max.