Historical, Cultural and Geographical Ties Between Pakistan and Iran

In order to get a vivid picture of Pakistan-Iran relations, the paper delves into the past with Iranian history and Iranian sphere of influence in South Asia. Both South Asia and Iran have ancient historical, cultural and religious ties since the times of the Cyrus the Great to the present. The Persian language and literature particularly the Persian classical poetry have left a great impression on sub-continent’s cultural and educational canvass. Pakistan-Iran border which was drawn by the British in the 1880s, remains still intact. Though the border is a wasteland with little agriculture but on the sea-front both the countries have access to the Strait of Hormuz which is of great strategic importance. Moreover, ethnic Baloch live on both sides of the border and crossborder and trade and livestock is the mainstay of cross-border economy. During the Cold War period, both Pakistan and Iran were subservient to the US policies against the Soviet Union; consequently, both received massive arms and equipment. This paper also indicates that during Mohammed Reza Shah’s time, the relations between Pakistan and Iran were quite friendly but they underwent a change after the Iranian revolution and during General Zia’s time. The main issues have been spelled out up-till 1979 and the minor frictions between the two countries could be managed through diplomacy. External pressures are also influencing the contemporary relations between the two countries and have put Pakistan in a dilemma. Historical and secondary sources have been used for the conduct of the study. Historical research has an important role to play in the Social Sciences. It helps us to understand the present by highlighting the past events.

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

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.