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Home > Comparison Between Chemosensitive and Chemoresistant Acute Myelogenous Leukemia in Term of Gene Expression of Selected Molecules Involved in Activation Transportation, Action and Metabolism of Ara-C and Anthracyclines

Comparison Between Chemosensitive and Chemoresistant Acute Myelogenous Leukemia in Term of Gene Expression of Selected Molecules Involved in Activation Transportation, Action and Metabolism of Ara-C and Anthracyclines

Thesis Info

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Author

Kulsoom, Bibi

Program

PhD

Institute

Ziauddin University

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Biochemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12937/1/Bibi_Kulsoom_Biochemistry_HSR_2018_ZU_Karachi_18.07.2018.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725769704

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INTRODUCTION: Acute myelogenous leukemia (AML) is the malignant transformation of hematopoietic cells belonging to myeloid series in bone marrow. It is an acute emergency and is fatal if not treated. Chemotherapy is the main treatment offered to AML patients. But persistent remission rate is not impressive. Although patients could be stratified into high, intermediate and low risk based on the karyotyping and cytogenetic abnormalities, there are patients in all risk groups who either remain resistant or relapse later in life. The sensitivity and resistance of a tumor cell may be related to the mechanisms that are involved in drug transportation, metabolism, and interaction with its target or efflux processes. OBJECTIVE: The aim of this study was to explore the relationship of gene expression of membrane transporters for drugs hENT1, MDR1, MRP2 and LRP, drug metabolizing enzymes dCK, CDA and dCMPD, drug target molecule topoisomerase IIa as well as the apoptotic pathway regulatory proteins Bax and Bcl-2 with the outcome of chemotherapy comprised of cytosine arabinoside (Ara-C), and daunorubicin (anthracycline group) in AML patients. METHODS: Bone marrow or blood or both were collected from 90 AML patients enrolled in this study during September 2011 to April 2017. Gene expression for the above mentioned genes was analyzed through real time or quantitative polymerase chain reaction (qPCR). Patients were labelled resistant or responsive based on complete remission (CR). Patients were also labelled “good” responders if they had persistent remission till the end of the study period, or “poor” responders if they were either resistant or presented with relapse. Gene expression was labelled low or high based on being lower or higher than that in normal healthy controls. RESULTS: Better clinical response was found associated with acute promyelocytic leukemia (APML) subtype (p<0.001), absent FLT3 mutation (p=0.02), higher gene expression of LRP in marrow (p=0.002) and Topo IIα in blood (p=0.005). APML patients had better overall survival (OS) at one year (p=0.03). Patients without FLT3 mutation had better one year OS (p<0.001) and six month OS (p=0.003). Higher LRP expression in marrow was associated with better one year OS (p=0.02). One year disease free survival (DFS) was better among those who had higher expression of LRP and CDA in marrow (p=0.007 and 0.03 respectively). Higher Topo IIα in blood was associated with better DFS at 6 and 12 months (p=0.04 and 0.04 respectively). The expression of other genes, i.e. hENT1, dCK, dCMPD, MDR1, MRP2, Bax and Bcl-2 did not correlate with clinical response, relapse, DFS or OS. Our logistic regression model predicted persistent remission vs. relapse (p=0.007), alive vs. dead (p=0.018) and good vs. bad responders (p<0.001). CONCLUSION: A diagnosis of APML, absence of FLT3 mutation, and higher expression of LRP and Topo IIa are the most important factors which predict better outcome in AML patients treated with Ara-C and anthracyclines.
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اُس در سے روپ مانگتے ہیں صبح و شام ؛رنگ


اُس در سے رُوپ مانگتے ہیں صبح و شام ؛ رنگ
جس کے طفیل رنگِ چمن کے تمام رنگ

فطرت کا حسنِ کُل ہے دھنک بن کے سرنگوں
جھکتے ہیں اُنؐ کے در پہ بصد اہتمام رنگ

وہ خاص ہے جو آپؐ سے منسوب ہو گیا
ورنہ تمام رنگ ہیں دنیا کے عام رنگ

حکمِ اذاں تھا بامِ حرم پر بلالؓ کو
دیکھا نہیں نبیؐ نے نسب ، قوم ، نام ، رنگ

دیکھو ذرا دھنک کے سبھی رنگ غور سے
کرتے ہیں سبز رنگ کا بھی احترام رنگ

عرفاںؔ! ادائے صاحبِ شق القمر سے قبل
ماہِ تمام رکھتا تھا اپنے تمام رنگ

Linguistic Expressions of Prophet Muhammad (ﷺ) As a Miracle in Arabic Language: A Study of Linguistic Miracles of Prophet Muhammad

Arabian Peninsula was famous for its language expertise and linguistic expressions at the time of Prophet Muhammad (ﷺ). The poets and language experts would spend most of their lives to attain excellence in Arabic language and literature. It was during such time that a man named Muhammad (ﷺ) emerged, whose linguistic expression was remarkable, accurate and amazing. He was also quite familiar with the dialects and accents of every tribe of Arabia. It was the surprising effect of this linguistic excellence that people tagged him with different titles such as Poet, Sorcerer, Kāhin (soothsayer), Majnūn (One possessed by Jinn), and insane man with insane message. Allah Almighty revealed Qur’ānic verses not only to answer such allegations but also entrusted him to present commentary of the Holy Qur’ān to the people who would called him illiterate. This article will try to find out the Qur’ānic commentary on the linguistic expressions of Prophet Muhammad (ﷺ) as a miracle of revelation. The method of research is descriptive analytical and historical. The discussion of verses of Qur’ān and the explanations of the experts of Qur’ān through the comments of orientalists have been included to support the arguments. First Part of the paper discusses status of Prophet Muhammad (ﷺ) as an illiterate man with his remarkable linguistic expressions of Qur’ān due to which he was awarded different titles such as poet, sorcerer and insane. The second part explains the Qur’ānic response to accusations on Prophet (ﷺ) raised by the opponents. In the third part, some intellectual arguments of Qur’ān and opinions of orientalist have been discussed to support the Qur’ānic responses in favor of linguistic expressions of an “Ummi” Prophet Muhammad (ﷺ) which is followed by findings and conclusion of the whole discussion.

Parasitic Potential of Encarsia Sophia Girault and Dodd on Bemisia Tabaci Gennadius Reared on Different Host Plants

Study was conducted at Insectary Biological Control Labs., IPMP, National Agricultural Research Centre (NARC) Islamabad under controlled environmental conditions at 26±1°C, 60±5% R.H. and 12:12 L: D photoperiod. Research experiments were done on whitefly Bemisia tabaci (Gennadius) which has been a serious pest in Pakistan for over the past two decades and its potential parasitoid Encarsia sophia (Girault & Dodd) as it is invasive, can be mass reared easily and able to parasitize more hosts. Results regarding host plant effect (cotton, brinjal and tomato) on B. tabaci biology concluded that development times, ovipositional preferences and survival of immature stages was strongly mediated by host plants selected for rearing. Among all the selected host plants, brinjal was considered as most suitable host in terms of developmental times (19.95±0.22 days) as compare to tomato (20.77±0.24 days) and cotton (23.05±0.23 days). Mean population density of eggs on cotton showed stronger preferences of B. tabaci for oviposition among three host plants with a mean number of (194.20±7.69) eggs laid/female with a mortality rate of (23.33%). According to the results, host plants selected for rearing of B. tabaci also showed significant effect on the biology of E. sophia. E. sophia developmental times (egg-adult) in B. tabaci instars was significantly shorter for parasitoids that emerged from brinjal (13.50±0.16 days) with highest percentage of parasitism (29.00±2.12) ranged from 15.00-55.00 and calculated higher emergence on brinjal 92.60±1.71% over other host plants. Results on population growth parameters also exposed brinjal as a good and effective host choice as parasitoid populations develops successfully on it with significantly higher net reproductive rate (Ro) 22.83 andintrinsic rate of natural increase (rm) 0.1043 with shorter mean generation time (Tc) 29.99 and doubling time (DT) 6.64 as compared to reared on cotton and tomato. The immature developmental stages observed for E. sophia were as eggs, 1st, 2nd and 3rd larval instars, pre-pupa and black pupae. Mean development duration from egg deposition till adult emergence was significantly different 12.61±0.13 days for female and 13.94±0.16 days for male. E. sophia preferred to oviposit in all four host instars of B. tabaci although preference differences were observed among host stages in terms of parasitism and feeding behaviours. Parasitism was observed higher on 3rd and 4th instars both in No-choice and Multiple- instar choice experiments but feeding was relatively higher in younger instars. Emergence was found both in light and dark conditions suggesting activity of parasitoid throughout 24h. Newly emerged parasitoid when placed under light source created ease for mating. Honey significantly prolonged the longevity of E. sophia adult. E. sophia fitness and efficacy in terms of fecundity, parasitism, developmental time, pupal survival and longevity was significantly altered by host instars. Almost all biological attributes of E. sophia were at its best developed on 3rd instars of B. tabaci with a faster developmental time (11.80±0.20 days), emerged more synchronously (86±2.66%) and lived longer (12.95±0.78 days) with maximum oviposition rate (62.50±1.69) eggs/female. Therefore it was concluded that larger hosts tended to produce better parasitoids than smaller hosts. The functional response studies determined that E. sophia have the ability to adjust itself at higher densities. E. sophia in relation to the density of host fitted the description of a type II functional response. Results commended a density of 30 instars as the highest critical density for parasitoid where parasitism rate and number of progeny was maximum with a minimum rate of super-parasitism. Host discrimination behaviour of E. sophia was also observed and it was concluded that newly emerged females NEF exhibit less ability to discriminate between the parasitised and unparasitised hosts over SHF and DEF. Females used to exploit minimum hosts when offered an unparasitized host while exploited maximum hosts when offered with a parasitized host as. Mean handling time for E. sophia was higher on unparasitized host while minimum for already parasitized host. The information will be useful in designing mass rearing protocols and in release trials of E. sophia for suppression of B. tabaci populations.