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Single Nucleotide Polymorphism-Based Association Studies of Bladder Cancer Patients

Thesis Info

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Author

Syeda Hafiza Benish Ali

Program

PhD

Institute

COMSATS University Islamabad

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2012

Thesis Completion Status

Completed

Subject

Natural Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/341

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727174932

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There are a growing number of studies conducted in different parts of the world to understand the genetic etiology of urinary bladder cancer (UBC), which is a life- threatening disorder. Therefore to find the susceptible genetic loci we conducted a case-control genetic association study on Pakistani urothelial carcinoma patients (N = 200) and healthy controls (N = 200). For this purpose, four types of sequence variations were studied viz. VNTR polymorphism of eNOS, Alu repeat variation of ACE gene, null polymorphisms of GSTT and GSTM genes and selected common variants of GSTP1, MTHFR, PSCA, TNFα, p21, TP53, CYP1B1, XPD, XRCC1, CAV1, PON1, IGFBP3, VEGFA, LEP, LEPR, PPARγ genes as well as intergenic 8q24 region. In addition to an overall risk assessment, these polymorphisms were also analyzed with respect to the smoking status as well as with respect to tumor grade and stage. Haplotype-based association analysis of variants residing in linkage disequilibrium were also carried out and a gene-gene interaction was studied with reference to combined genotype analysis of functionally related genes. The risk variants of GSTM, LEPR, ACE, PSCA and 8q24.21 locus (rs9642880 and rs6983267) were found to be associated with significantly higher risk while IGFBP3 variant and haplotypes of CAV1 and MTHFR were found to be associated with reduced risk of UBC in the overall comparison of cases and controls. In the gene-smoking interaction CYP1B1, p21 (Ser allele), ACE and rs9642880 conferred a high UBC risk in smokers while LEPR and PSCA variants were found to be associated with increased risk of bladder oncogenesis in non-smokers only. In addition, p21 (Arg allele) was found to be associated with reduced UBC susceptibility in smokers while IGFBP3 and CAV1 haplotypes protected against urothelial carcinoma of the bladder in non-smokers only. GSTM0 and the risk allele of rs6983267 did not show a gene-smoking interaction because of their significant risk contribution in both smoker and non-smoker groups. With reference to tumor grade and stage, a trend of similar genetic etiologies was observed in low grade and non-invasive tumor, while the high grade and invasive tumor types were also found to have common genetic etiologies which were different from the former group. GSTM0, LEPR and rs9642880 were found to be associated with enhanced risk of low grade as well as non-invasive bladder carcinoma. GSTT0, CAV1, PSCA and PPARγ were found to predispose individuals to an elevated risk of ixhigh grade and invasive tumor. ACE and rs6983267 were non-specifically associated with both low and high grades as well as with non-invasive and invasive tumors. IGFBP3 SNP protected against low and high grade as well as against non-invasive stage. The haplotypes of MTHFR were found to confer a high risk of non-invasive tumor while providing protection against MIBC. In brief, the present study revealed the association of some of the genetic variants to the overall disease susceptibility in addition to some gene-smoking and gene-gene interactions.
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مولانا احمد علی

مولانا احمد علی
افسوس ہے پچھلے دنوں مولانا احمد علی اورمسٹر شعیب قریشی نے داعی اجل کولبیک کہا اوررہ گزائے عالم جاودانی ہوگئے۔مولانا احمدعلی حلقۂ دیوبند کے اکابر و مشائخ میں سے تھے۔بلند پایہ عالم، وسیع النظر مفکر اوردرویش صفت بزرگ ہونے کے علاوہ اونچے درجہ کے صاحب معرفت وباطن بھی تھے۔قرآن مجید کی تفسیر اوراُس کی تعلیم وتدریس سے خاص شغف تھااوراُس کا بڑااہتمام کرتے تھے، دارالعلوم دیوبند اوردوسرے مدارس عربیہ کے فارغ التحصیل طلبا اسی غرض سے لاہورجاتے اورچند ماہ قیام کرکے مولانا کے مخصوص درس قرآن سے مستفید ہوتے تھے۔پنجاب کے انگریزی تعلیم یافتہ حضرات بھی موصوف کے زیر اثر تھے اوراُن کی اچھی خاصی تعداد اس درس میں پابندی سے شریک ہوتی تھی۔ پنجاب میں مولانا کی ذات جواحیاء دینی،روحانی واخلاقی تعلیم وتربیت اورنشروتبلیغ علوم ومعارف قرآنیہ کے لیے وقف تھی۔ مرجع عوام وخواص تھی۔تقریر موثر اور دلپذیر ہوتی تھی مگر مجلس میں کم سخنی وکم گوئی اُن کی خو تھی۔زندگی بڑی سادہ تھی، تکلف، تصنع اورمادی آرائش وزیبائش سے نفرت تھی۔ان خوبیوں کے علاوہ مجاہد فی سبیل اﷲ بھی تھے۔تحریک خلافت اوراُس کے بعد جدوجہد آزادی میں ہمیشہ جمعیۃ علماء ہند کے ساتھ رہے۔مولانا عبیداﷲ سندھیؒ کے داماد تھے۔اس تعلق سے اُن کومولانا سے استفادہ کا زیادہ موقع ملا تھااوراُس کااثر اُن کے درس قرآن میں اورعام تقریروں اورگفتگوؤں میں بھی ظاہرہوتاتھا۔قیام پاکستان کے بعد سے بڑے بڑے اہم مسائل رونما ہوئے اوربعض اوقات علماء کے لیے سخت ابتلا و آزمائش کے مواقع پیداہوگئے، مگرمولانا نے اعلان حق اوراعلائے کلمۃ اﷲ میں کبھی بھی کوتاہی یاپہلوتہی سے کام نہیں لیا۔اُن کواس کی سزابھگتنی پڑی۔مگر انھیں اس کی کبھی پروا نہیں ہوئی۔اب ایسے علمائے حق کہاں ملیں گے؟جوجاتاہے اپنا صحیح جانشین وقائم مقام چھوڑ کرنہیں جاتا۔ اللھم بردمضجعہ وارحمہ رحمۃً واسعۃً۔ [اپریل۱۹۶۲ء]

 

شاہ ولی اللہ كا نظریہ اخلاق و معاشرت

His distinction was that he reflected over the Islamic system and applied it upon the modem age. He proved that the teachings of Islam cover not only faith, beliefs and rituals of worship but also rule all the aspects of social and moral values of a Muslim. He proved with profound arguments that these fundamental principles prevail and govern the Muslim society and its ethics. Shah Waliullah had a broad vision and a versatile approach towards the different aspects of political, moral and social behaviors. The most important thing about his contributions is that his views are widely accepted and welcomed by the scholars who came after him.

A Comparative Study of Management Practices in Multinational and National Organizations in Pakistan

Today’s organization are facing the challenge and threats then ever before due to rapid changes in the business environment. It is not only the change itself; it is the pace of change and the speed of the communication of that change that presents such a great challenge. Thus this creates the need that the profession of management must be harmonized to cope with the speed of these changes. The specific objectives of this study are to obtain an understanding of the general management practices of organizations operating in Pakistan vis-a vis understanding the differences in management practices among national and multinational organizations. A large number of studies and analysis have been conducted in developed countries like USA, UK, Japan, France, Germany etc to gain an insight of the specific management practices and its peculiar aspect that are responsible for performance improvement of organizations. The research in this area is minuscule in Pakistan with a limited number of certain agencies whose research was circumscribed within a restricted domain. However the contribution of Lahore University of Management Sciences (LUMS) is worth mentioning. This study aimed at comparing management practices among national and multinational organizations; therefore the target population was a specified number of national organizations of size medium to large from various fields compared with multinational organizations of various disciplines. Since the basic parameters of management are same for any type of organization, the focus of study was concentrated at its various aspects such as planning mechanism, leadership style, motivation and teamwork, production management, and corporate social responsibility.The diversity of the organizations provided an opportunity to obtain an indepth investigation and determine the causes for the similarity and dissimilarity of the management attributes, which is the main essence of this study. Organizations serve as the backbone for the economic development and prosperity of a country. Pakistan though being an agricultural country but industrialization precedes agriculture in the sense that agricultural developments and advancements is possible through industries only and industries can thrive if they are successful in applying the appropriate and timely management techniques.Pakistan is a country which is of strategic importance to the world; it serves as a hub by linking the economies of the world. The location is strategic with a view that Pakistan is the nucleus of three powerful economies namely Central Asian economy including China, South Asian economy including populous India, Bangladesh and Indonesia; and on the west Middle East West Asian economies which are major sources of oil supply and reserves to the rest of the world.China is one of the fastest growing country in the Central Asian economy. According to PricewaterhouseCoopers (PWC) one of the top business consultancy in its report said that by 2030 the top ten world economies would be China, United States, India, Japan, Brazil, Russia, Germany, Mexico, France and Britain. The Current ten largest economies according to 2008 data from the International Monetary Fund (IMF) are the United States, Japan, China, Germany, France, Britain, Italy, Russia, Spain and Brazil. The World Bank in its annual report 2009 of ‘Ease of Doing Business’ recognized Pakistan as the 85th most business friendly country in the world. The Ease of Doing Business index is an index created by the World Bank and it is based on the average of ten sub-indicators with the input and verification of more then 5,000 government officials. In this scale Singapore stands top and Central African Republic stands last on serial 183 in the list. Pakistan’s position as compared to neighboring countries is; China is ranked 89, India 133, Afghanistan 160 and with respect to South Asian Countries Pakistan’s rank is better as compared to Sri Lanka which holds 105, Bangladesh 119 and Nepal 123.Unfortunately for the last few years the country is facing a situation of uncertainty and crisis that it had not faced before. The internal turmoil and chaos within the country, the rising rate of inflation, deteriorating law and order situation, terrorism, extremism, shortages of general commodities, electricity crisis, foreign policy issues, and many other related factors has affected the corporate world also that demands an effective management system to survive in the face of these competitive forces.A comparative study of management practices reveals that although Pakistan is suffering a number of anomalies but still the country is ranked to be a business friendly country and their exist immense potential that can be materialized and explored. This requires that the organizations must consider those management areas which need to be focused such as managing quality and productivity through effective planning and proper leadership without creating an imbalance condition in organizations responsible for creating frustration among employees. Thus the organizations in Pakistan have the opportunity to play their roles in this regard by stressing for an effective management system that will allow them to realize benefit from this opportunity.