Mathematical Modeling of Human Glioma Growth Based on Brain Topological Structures: Study of Two Clinical Cases

Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor), and an advanced state when infiltration starts (malign tumor). Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality

MANAGEMENT OF HYDROCEPHALUS IN POSTERIOR CRANIAL FOSSA TUMORS

Treatment of hydrocephalus in posterior fossa tumors in children is still a matter of controversy and different centers have their own routines. In this regard, hospital records of all children with posterior fossa tumors treated in our center during the interval of 1985-1995 were reviewed. Patients’ demographic and diagnostic data were analyzed and the frequencies of shunting procedures were determined. Fisher exact test was employed to compare the frequency of postoperative complications in different groups. A total of 108 patients with age ranging from 3 months to 18 years and a male to female ratio of 1.5 comprised the study population. Ninety-nine cases had hydrocephalus at the time of diagnosis and 81 patients underwent preoperative shunting. Of the remaining 18 patients, 13 underwent external ventricular drainage at tumor operation session plus preoperative corticosteroid therapy. The rest of the patients got no primary treatment for hydrocephalus. Three of these 5 patients had postoperative shunting after tumor removal, but the other 2 remained shunt free. The rate of postoperative complications including cerebrospinal fluid leakage and septic meningitis were significantly lower in patients with preoperative shunting. The results of this study are in favor of those that approve the effect of preoperative shunting in decreasing postoperative complications. This is well established when the tumor size is big or when the diagnosis of posterior fossa tumor is made in later stages or when hydrocephalus is severe. It could be concluded that preoperative shunting can decrease the rate of postoperative complications

Prevalence of the rs7903146C>T polymorphism in TCF7L2 gene for prediction of type 2 diabetes risk among Iranians of different ethnicities

Mojgan Allahdini,1 Behnam Kamalidehghan,2 Leila Akbari,3 Parisa Azadfar,3 Ali Rahmani,1 Fatemeh Ahmadipour,2 Goh Yong Meng,4 Abbas Masserrat,5 Massoud Houshmand6 1Department of Molecular Biology, Ahar Branch Islamic Azad University, Ahar, Iran; 2Pharmacy Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Biology, Sciences and Research Branch, Azad University, Tehran, Iran; 4Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia; 5Department of Medical Genetics, Taban Clinic, 6Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran Background: Pharmacogenetics is the study of genetic polymorphisms affecting responses to drug therapy. The common rs7903146 (C>T) polymorphism of the TCF7L2 gene has recently been associated with type 2 diabetes (T2D). In this study, prevalence of the rs7903146 (C>T) polymorphism in the TCF7L2 gene for prediction of T2D risk was examined in an Iranian population of different ethnicities.Methods: The prevalence of rs7903146 (C>T) and the predicted phenotypes, including extensive metabolizers, intermediate metabolizers, and poor metabolizers were investigated in blood samples of 300 unrelated healthy individuals in an Iranian population, including Fars, Turk, Lure, and Kurd, using polymerase chain reaction restriction fragment length polymorphism and direct genomic DNA sequencing.Results: The homozygous wild-type (C/C), heterozygous (C/T), and homozygous (T/T) allelic frequencies of rs7903146 (C>T) in the TCF7L2 gene were 29% (extensive metabolizers), 66.34% (intermediate metabolizers), and 4.66% (poor metabolizers), respectively. The C/C, C/T, and T/T genotypic frequencies of the rs7903146 (C>T) allele were significantly different (P<0.01) among Iranians of different ethnicities. The frequency of the homozygous T/T variant of the rs7903146 (C>T) allele was significantly low in the Lure (P<0.01) and high in the Fars (P<0.001) ethnicities. Additionally, the frequency of the T/T variant of the rs7903146 (C>T) allele in the South of Iran was the highest (P<0.04), while the East of Iran had the lowest frequency (P<0.01).Conclusion: The prediction of rs7903146 (C>T) is required in drug research and routine treatment, where the information would be helpful for clinicians to optimize therapy and adverse drug reactions and predict drug response in individuals at risk of T2D. Keywords: pharmacogenetics of type 2 diabetes (T2D), transcription factor 7-like 2 gene, TCF7L2, rs7903146 (C>T) SNP, Fars Turk Lure and Kurd, Iranian populations of different ethnicitie