Search

Sickle cell disease (SCD) is a disease of abnormal hemoglobin associated with severe clinical phenotype and recurrent complications. Hydroxyurea (HU) is one of the US-FDA approved and commonly used drug for the treatment of adult SCD patients with clinical -severity. However, its use in the pediatric groups remains atypical. Despite a high prevalence of the disease in the state Chhattisgarh, there is a lack of evidence supporting its use in pediatric patients. This study aimed to evaluate the pharmacological and clinical efficacy and safety of HU in a large pediatric cohort with SCD from Central India. The study cohort consisted of 164 SCD (138 Hb SS and 26 Hb S beta-thalassemia) children (≤14 years of age) on HU therapy, who were monitored for toxicity, hematological and clinical efficacy at baseline (Pre-HU) and after 24 months (Post-HU). The results highlight the beneficial effects of HU at a mean dose of 18.7 ± 7.0 mg/kg/day. A significant improvement was observed, not only in physical and clinical parameters but also in hematological parameters which include fetal hemoglobin (Hb F), total hemoglobin, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, when evaluated against the baseline. We did not observe any significant adverse effects during the treatment period. Similar results were obtained on independent analysis of Hb SS and Hb Sβ patients. These findings strengthen the beneficial effect of hydroxyurea in pediatric population also without any serious adverse effects and builds up ground for expanding its use under regular monitoring. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions. [ABSTRACT FROM AUTHOR]

TP53 gene encoding polymorphisms is a risk allele in terms of carcinogenesis. Here, we studied the risk assessment and association of TP53 to understand the cancer biology and behaviour in cervical cancer patients and possible anticancer drug development interfering with p53 protein production. TP53 gene encodes a central protein of apoptosis pathway p53 and its allelic variant has been postulated to play a vital role in carcinogenesis in addition to a variety of neurodegenerative disorders. We undertook a case control study, to examine the possible association of TP53 gene codon 72 polymorphism in leukocyte DNA from a total of 200 subjects (100 controls and 100 cases). TP53 codon Arg72Pro (rs1042522) genotype was identified using allele specific PCR and RFLP with statistical analysis using Vassar Stats (online). In Chhattisgarh population, individuals with GC and GG genotypes of TP53 gene codon 72 polymorphism has a significantly higher risk of cervical cancer (OR=6.36, 95%CI=2.8-14.03 and OR=7.42, 95%CI=3.5-15.9) as compared to CC genotype (OR=1) which was taken as reference. The 'G' allele was found to confer a significant risk of cervical cancer (OR= 3.69, 95%CI= 2.40-5.5) compared to 'C' allele. The present case control study demonstrated the prevalence of the Arg/Arg (GG) genotype in women with cervical cancer among Chhattisgarh population. [ABSTRACT FROM AUTHOR]

The prevalence of sickle cell disease in India is very high. Hb F is one of the most powerful modulators of disease severity in sickle cell disease patients. It was traditionally thought that the disease is milder in Indian sickle cell disease patients predominantly due to the Arab-Indian haplotype characterized by theHBG XmnI [rs7482144 (G>A)] variant, which is associated with increased Hb F levels. In the current study, we investigated the Hb F levels in individuals with the rs10128556 (C>T) variant and also determined its linkage with theHBG XmnI variant. The present study was conducted on a cohort of 275 individuals, which consisted of 221 patients with sickle cell disease and 54 patients with sickle cell trait. Analysis of hemoglobin (Hb) fractions and variants was done on the high performance liquid chromatography (HPLC) system. Genotyping for rs10128556 was done by direct sequencing of the products. Mean Hb F levels in the sickle cell disease patients was 19.36 ± 6.79. The genotypic frequencies for rs10128556 were 82.0% (TT), 16.7% (CT) and 1.3% (CC) for sickle cell disease patients. The minor C allele resulted in 52.0% decrease in Hb F levels when homozygous and 7.0% decrease when heterozygous. The rs10128556 single nucleotide polymorphism (SNP) was in strong but not complete linkage with theHBG XmnI variant. In conclusion, the study determined for the first time the frequency and association of rs10128556 in Indian sickle cell disease patients with Hb F. It also established that it was not in complete linkage with theHBG XmnI variant in this high risk population. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is life-threatening hemoglobinopathy prevalent in India, Sub-Saharan Africa and Middle East. Inflammation plays a pivotal role in disease process and involves intricate interaction among leukocytes, platelets, sickle erythrocytes and vascular endothelium. Available disease modifying therapies are hydroxyl-urea and blood transfusion. Therefore, it is of interest to develop improved pharmacological agents for SCD. We report up-regulated genes in steady state and vaso-occlusive crisis using analysis of gene expression data obtained by microarray experiment for SCD as potential targets. The association of these targets with inflammation in pathway analysis is also documented.