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Home > Host and Viral Factors in the Development and Progression of Human Papillomavirus Hpv Induced Cervical Cancer

Host and Viral Factors in the Development and Progression of Human Papillomavirus Hpv Induced Cervical Cancer

Thesis Info

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Author

Ilahi, Naureen Ehsan

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/123456789/10068/1/PhD%20Thesis-Naureen%20Ehsan%20Ilahi-%20NUST201290070TPASAB8012F.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726377450

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A wide range of diseases have papillomaviruses (PVs) as their causative agent and human papillomaviruses (HPVs) are behind a great portion of anogenital and some non-genital malignancies worldwide. In Pakistan fewer reports are based on occasional testing from the different regions of the country. Present study investigated incidence and etiological involvement of HPV in cervical cancer in Pakistan. Moreover, prevalence of HPV in other anogenital and non-genital cancers such as breast and lung cancer was also observed in the study subjects. This study also aimed at exploring the functional aspect of HPV E5 oncoprotein. HPV E5 has been documented as a significant player in the productive stage of the viral life cycle and is seen to exert its effect through enhancing the epidermal growth factor receptor (EGFR) pathway. In epithelial malignancies such as HPV-positive cervical cancer, EGFR is among the most frequently activated proto oncogenes. Negative regulator of EGFR family include LRIG1 (leucine-rich repeats and immunoglobulin-like domains protein 1) which has been recently discovered. Though E5 role in enhancing EGFR signaling is largely documented but all aspects of the receptor signaling have not been taken under consideration such as the possible interplay between E5 and LRIG1 during EGFR signaling. In order to address the possible interplay between viral factor E5 and host factor LRIG1 that may lead to the development of HPV related disease, first role of LRIG1 in cervical cancer cell lines was studied in relation to EGFR. Further, human foreskin keratinocytes (HFKs) expressing a functional E5 and E5 knockout counterparts were utilized to observe the effect of E5 on LRIG1 and its activity. Following differentiation, HPV18 HFKs began expressing functional E5 in semisolid medium, and a reduction in LRIG1 protein expression was seen as compared to the ABSTRACT xx knockouts suggesting the possible role of E5 in downregulating EGFR negative regulation pathway. Messenger RNA and protein expression analysis confirmed the decrease in LRIG1 expression in accordance with the expression of E5 as well as impact of E5 in delaying differentiation and downregulating LRIG1 at varying levels of differentiation in keratinocytes. It can be speculated that hijacking control from LRIG1, E5 provides that ‘added value’ to the HPV types expressing it. However through co-immuno-precipitation experiment no physical binding between the two proteins which could be responsible for this effect was observed. Thus it may be concluded that E5 way of affecting LRIG1 may not be direct but is potent enough to render the protein incapable of performing its function. Moreover it was seen that by physically blocking tyrosine kinase domain of EGFR, LRIG1 levels were successfully restored in E5 expressing keratinocytes. It also suggests that, if utilized, LRIG1 may act synergistically with tyrosine kinase inhibitors in downregulating EGFR pathway in an HPV infection. In conclusion present study helped us to explore the unaddressed role of HPV E5 in influencing negative regulation of EGFR pathway. Thus, the study provided basis for future studies which may target E5 as an important oncoprotein of HPV and LRIG1 as a tumor suppressor for therapeutic purpose.
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شام کا دوسرا سفرِ تجارت

شام کا دوسرا سفر تجارت
حضورؐ پچیسویں سال، حضرت خدیجہ کا مال تجارت’’ بطریق مضاربت‘‘لے کر شام کی جانب تجارت کے لیے تشریف لے گئے۔یہ اس قول کی بنا پر کہ ابو طالب نے حضورؐ سے عرض کیا ‘ چونکہ میرے پاس اب مال بالکل نہیںرہا ہے اور قریشیوں کا قافلہ بغرض تجارت جانے والا ہے۔ لہٰذا خدیجہ بنت خویلد ؓ سے جا کر کہو ،وہ قریش کے مال دار لوگوں میں سے ہیں اور لوگوں کو مضاربت کے طور پر مال تجارت دے کر بھیجتی ہیں تو اگر آپ خود اپنے لیے چاہیں گے تو وہ یقیناََ مال تجارت آپ ﷺکو بھی دے دیں گی اور ممکن ہے کہ اس طرح کچھ نفع حاصل ہو جائے ۔لیکن صحیح ترقول یہ ہے کہ سیدہؓ خود کسی ایسے امین کی متلاشی تھیں جسے وہ اپنا مال تجارت سپرد کریں اور وہ حضورؐ سے زیادہ کسی کو امین نہ پاتی تھیں ۔ چونکہ حضور اکرمﷺ کو تمام قریش اظہارِ نبوت سے قبل ’’محمد ﷺ کو امین‘‘ کہا کرتے تھے۔ لہٰذا سیدہ خدیجہؓ نے کسی کو آنحضرت ﷺکے پاس بھیجا کہ اگر میرا مال تجارت آپ لے جائیں اور حق تعالیٰ اس میں نفع دے تو جتنا نفع آپ مناسب خیال فرمائیںلے لیں۔ ایک روایت میں ہے کہ دو گنا مال دوسروں کی نسبت دوں گی۔ سید عالمﷺ نے ابو طالب کے مشورہ کو قبول فرمایا ۔اس کے بعد سیدہؓ نے اپنا غلام جس کا نام میسرہ تھا اور اپنا ایک مخصوص آدمی جس کا نام خزیمہ تھا آپ ؐ کی خدمت کے لیے ساتھ کر دیا۔ آپؐ جب بصریٰ پہنچے تو وہاں ایک صومعہ یعنی کلیسا تھا جس میں نسطورا راہب رہتا تھا۔ اس نے حضور ﷺ کو ایک ایسے درخت کے نیچے جلوہ افروز دیکھا جس کے بارے میں خبر تھی کہ اس درخت کے نیچے سوائے نبی...

المقاصد عند الإمام الشاطبي

Scholars of the Usul -early and recent- have paid utmost importance to the Maqâsid al-Shariah or the Objectives of Shariah and tried to substantiate, associate and link them with its sources, Qur’an and Sunnah, then to derive from them the Legislator’s or the Shari‘s purpose, the revelation’s true purpose and how it benefits the creatures in terms of promoting what is in their interest and shunning away what is harmful. These objectives became the point of interest for the jurists and scholars who toiled to understand the texts and what they connoted and they continue to venture into its depths and extract its treasures. It becomes quite evident from their exegeses of Qur’an and the Prophetic Traditions and elucidations of the juristic principles and issues. Imam al-Shâtibī and Ibn ‘Ashoor are two such scholars in this field who studied the Objectives of Shariah and contributed to this discipline so greatly that they became reference points for those who came after them. The basic principles in the field that were inferred by them are still its pillars. The Objectives of Shariah are divided into four kinds with reference to their benefits: the necessities, needs, improvements and supplements. The necessities are further divided into protection of Deen, protection of self, of intellect, of possessions and of race among others. Prudence demands that all means should be employed to safeguard these necessities. Thus knowing the Objectives of Shariah and their promulgation among the masses is quite important for the society since it leads towards promotion of the beneficial and shunning away the harmful elements in it.

Possibilities and Practicalities of Enriching the Class 5 English Curriculum

This study examines how the English curriculum of Class 5 is enriched in a Junior primary section of a private school in Karachi Pakistan. The top - down approach requires teachers to follow the National Curriculum as it is, particularly, in Government schools. Most teachers in the Government context have not seen it physically. Hence, teaching in the perspective of those teachers may be to make students cram outdated factual information and remain within the boundaries of “textbook”, which is often mixed up with the curriculum. Little authority is given to teachers to take it further to enhance the learning of the students. On the other hand, few private schools have embarked upon the process of “curriculum enrichment”, because the existing National Curriculum appears to have failed to meet the varying needs and demands of students, and their voices are often unheard with respect to their interests. Moreover, societal and technological changes taking place locally and globally demand that our National Curriculum's scope becomes wider and in depth, bringing diversity and richness in it in order to be able to face the future challenges. Qualitative case study design, studying two classrooms, was used to construct the picture of the participants' understanding about the main research and subsidiary questions. Data were collected through the enriched English curriculum of Class 5 of the school where I conducted this research. The research participants' lesson observations, structured and unstructured interviews of the research participants, interviews of the Vice Principal, the Coordinator and the students, and attending the Coordination Meeting where teachers' and students' concerns and enrichment activities developed by the English teachers are discussed. Analysis of the data revealed that the school is enriching the English curriculum of Class 5 through various strategies, for example, material, organizational, pedagogical, paradigmatic, relational and students' ideas and experiences. The school Management fully supports English teachers in the curriculum enrichment. The teachers welcome students' contributions who have the potential to enhance the curriculum. On the other hand, the English teachers need to develop further understanding about the curriculum and its enhancement so that they could effectively achieve the objectives for curriculum enrichment. Moreover, critical inquiry, in terms of specific enrichment activities and supplementary books, is also needed. Based on these findings, the importance and the recommendations of the study in terms of the teachers' and my own practice, and literature on the perspectives of different stakeholders about curriculum