Tariq Saeed

Five most common prognostically important fusion oncogenes are detected in the majority of Pakistani pediatric acute lymphoblastic leukemia patients and are strongly associated with disease biology and treatment outcome.

BACKGROUND AND OBJECTIVES Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. METHOD We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. RESULTS Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival (43.7±4.24 weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). CONCLUSIONS This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

Prognostically Significant Fusion Oncogenes in Pakistani Patients with Adult Acute Lymphoblastic Leukemia and their Association with Disease Biology and Outcome

BACKGROUND AND OBJECTIVES Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. METHODS We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. RESULTS Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(9)/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. CONCLUSIONS This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

Changes in skin mechanical properties after long-term application of cream containing green tea extract

Background and aims: We studied longterm application of cream containing green tea extract, to obtain knowledge of its effects on epidermal mechanics by 2-mm diameter Cutometer probe. Methods: Using this non-invasive device, we assessed the effects of green tea extract cream on skin mechanical properties. Healthy male volunteers (n=10) were included in this study, which lasted 60 days. The biomechanical properties of the skin were examined by a non-invasive suction device (Cutometer) and the cheeks were defined as the test area. Results: Statistically significant (p<0.05) results were notable for the R6 (Uv/Ue) parameter with respect to time (ANOVA); R0, R2 (Ua/Uf) and R7 (Ur/Uf) parameters were found statistically not significant by ANOVA. This study demonstrates that green tea formulation has a certain effect on R6 (Uv/Ue) parameter when applied regularly for a certain period of time. Conclusions: These results indicate that the formulation has no pronounced overall effects on skin elastic or biological properties, but significant R6 (Uv/Ue) values indicate that it does have definite effects on the viscoelastic properties of the skin.

Formulation and Characterization of a Cream Containing Terminalia chebula Extract

Background: This study aimed to formulate a water-in-oil emulsion (formulation) of Terminalia chebula versus its vehicle (base) as control, and investigate its effects on skin melanin, skin erythema, skin moisture content, and transepidermal water loss (TEWL). Material and Methods: Base containing no active material, and formulation containing 5% concentrated extract of T. chebula, were developed. Different stability parameters were monitored at 8, 25, and 40 °C, as well as 40 °C + 75% relative humidity, for a period of 4 weeks. It was concluded that the creams remained stable at all storage conditions. Both base and formulation were applied to the cheeks of human volunteers for a period of 8 weeks. Different skin parameters were monitored every week to measure any effect produced by these creams. Results: Changes in TEWL produced by base and formulation were insignificant (p > 0.05) with respect to time while significant (p ≤ 0.05) with respect to base and formulation. The skin moisture content increased after the application of formulation throughout the study period; this effect was insignificant (p > 0.05) with respect to time while significant (p ≤ 0.05) with respect to base and formulation. Both base and formulation showed insignificant (p > 0.05) effects on skin melanin content with respect to time. Skin erythema was reduced by the formulation. Both base and formulation produced statistically insignificant (p > 0.05) effects on skin sebum. Conclusion: Both creams were aesthetic with respect to sensory evaluation. T. chebula topical cream showed a positive rejuvenating effect on human skin. Hopefully, this study will encourage more attention towards the research and utilization of herbal medicines.

Medicinal potentials of Alpinia galanga

Faculty of Eastern Medicine, Hamdard University, Karachi, Pakistan. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur Pakistan. University College of Pharmacy, The University of Punjab Lahore, Pakistan. Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan. School of Pharmacy, The University of Lahore, Islamabad Campus, Islamabad, Pakistan.