• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3117-3122
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• 2016

Background: Health-care research is a neglected discipline in Pakistan and research related to esophageal cancer (ranks 9th in Pakistani males and 5th in females) is no exception in this regard. Particularly, there are no data available to delineate the overall status of esophageal cancer epidemiological studies in Pakistan. This study describes the first ever effort to make a systematic quantification, in an attempt to provide a road-map to all stakeholders for designing appropriate epidemiological, diagnostic and therapeutic strategies. Materials and Methods: International (PubMed, ISI Web of Knowledge) and local (PakMedinet) scientific databases as well as Google search engine were searched using specified keywords to extract relevant publication. Well-defined inclusion criteria were implemented to select publications for final analyses. All data were recorded by at least 3 authors and consensus data were entered into and analyzed for descriptive statistics (such as frequencies, percentages and annual growth rates) using Microsoft Excel and SPSS software. Results: A total of 79 publications fulfilled the inclusion criteria including 20 publications for which full texts were not available. Of the 79 publications, 59 (74.6%) were original/research publications, 5 (6.3%) were case reports, 4 (5.1%) were research communications, 2 (2.5%) were review articles, 1 was (1.2%) correspondence and 8 (10.1%) were undefined categories. Only 13 (<20%) cities of Pakistan contributed towards the 79 publications. On average, only 1.9 relevant publications/year were published from 1976 (year of first publication) to the present. Alarmingly, a decline in the annual growth at -4.1% was recorded in the last six years. Conclusions: Esophageal cancer research is largely unfathomed in Pakistan. Urgent/dramatic steps are required by all concerned to address this common (and under reported) cancer of Pakistan.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.47-54
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• 2014

Objectives : This study was undertaken to verify the effect of Gangjihwan(Di-fatty, DF) composed with Pakistani Ephedra Herba on nonalcoholic fatty liver disease(NAFLD) using high fat diet-fed male mice. Method : Eight-week old C57BL/6N mice were used for all experiments. Standard chow diet-fed mice were used as normal group and high fat diet-fed NAFLD mice were randomly divided into 5 groups: control, atorvastatin, DF(1), DF(2) and DF(3). After 8 weeks, mice were treated with water, atorvastatin(10mg/kg) and DF(40, 80, 160mg/kg) for 8 weeks. And we investigated body weight gain, plasma lipid and glucose metabolism, histological analysis for liver on the mice. Results : Compared with controls, DF-treated mice had very significantly lower body weight gain and lower visceral adipose tissue weight, the magnitudes of which were prominent in DF(3). Consistent with their effects on body weight gain, DF-treated mice had lower blood total cholesterol and triglyceride level compared with controls. Consistent with their effects on body weight gain and blood plasma lipid level, DF-treated mice had lower liver weight and hepatic lipid accumulation of DF-treated groups was significantly decreased than control group. Also Blood plasma AST, ALT and ${\gamma}$-GT concentration were not changed by DF, and these results may indicate DF do not show any toxic effects. Conclusions : These results suggest that DF effectively improves NAFLD. DF reduces liver weight and prevents lipid accumulation of hepatocyte by reducing body weight gain and modulating blood plasma lipid metabolism levels.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5469-5475
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• 2012

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 ($43.7{\pm}4.24$ 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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3349-3355
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• 2012

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-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than $50{\times}10^9/l$. 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 of5 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.

• Journal of Life Science
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• v.31 no.5
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• pp.453-463
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• 2021

Hearing loss is a group of clinically and genetically heterogeneous disorders characterized by congenital- to adult-onset deafness with frequent additional symptoms such as myopathy, nephropathy, and optic disorders. It is commonly divided into two types: syndromic, with no other symptoms, and nonsyndromic, with other symptoms. Autosomal recessive hearing loss is relatively frequent in Pakistan, which may be due in part to frequent consanguineous marriages. This study was performed by whole exome sequencing to determine the genetic causes in two Pakistani consanguineous families with autosomal recessive hearing loss. We identified a pathogenic homozygous variant (p.Leu326Gln in MYO7A) in a family with prelingual-onset hearing loss and two variants of uncertain significance (p.Val3094Ile in GPR98 and p.Asp56Gly in PLA2G6) in a family with early-onset hearing loss concurrent with muscular atrophy. The missense mutations in MYO7A and PLA2G6 were located in the highly conserved sites, and in silico analyses predicted pathogenicity, while the GPR98 mutation was located in the less conserved site, and most in silico analysis programs predicted its nonpathogenic effect. Homozygosity mapping showed that both alleles of the homozygous mutations identified in each family originated from a single founder; spread from this single source might be due to consanguineous marriages. This study will help provide exact molecular diagnosis and treatment for autosomal recessive hearing loss patients in Pakistan.