Kashif Ali

Mutational spectrum of Gelsolin and its down regulation is associated with breast cancer.

Cytoskeletal rearrangement occurs in variety of cellular processes and involves a wide spectrum of proteins. Gelsolin super family proteins control actin organization by severing and capping filament ends and nucleating actin assembly. Gelsolin is the founding member of this family and plays important role in pathogenesis of human neoplasia. This study aimed to investigate the germline mutations and expressional profile of Gelsolin in human breast cancer tissues. For germ line screening PCR-SSCP technique was used while expression was analyzed through quantitative real time PCR. Different types of mutations were observed in Gelsolin coding regions on exons 4, 10, 11, 14 and 15. These mutations include 3 missense nonsynonymous substitution mutations, 2 deletions, 1 insertion and 1 synonymous substitution mutation. Gelsolin transcript level was found significantly lower in breast tumor tissues compared to control samples (p=0.03). Low level of Gelsolin was found in metastatic patients (p=0.002) and patients who died from breast cancer (P=0.03) compared to disease free patients at final follow up. This study shows that level of Gelsolin is down regulated in breast cancer tissues and is linked with metastasis development and death in patients. It is concluded that genetic changes in coding regions of Gelsolin can potentially contribute to genetic instability. These genetic variations and expressional correlation with patient survival may prove to be of significant importance.

New Thirring optical solitons with vector-coupled Schrödinger equations in birefringent fibers

The article studies the dynamics of Thirring optical solitons in birefrigent fibers with vector-coupled nonlinear Schrödinger equations. The -expansion scheme has been used to extract the dark and singular soliton solutions along with constraint conditions. It may also be noted that a couple of other solutions known as singular periodic solutions, fall out as a by-product of this scheme

OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data

In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3′UTR mutations, three missense mutations, and a nonsense mutation. Significantly (p < 0.001) increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3′UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (p < 0.009). Similarly ~14-fold increased risk was associated with Val159Gly (p < 0.01), ~17-fold with Gly221Arg (p < 0.005), and ~18-fold with Ser326Cys (p < 0.004) in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold (p < 0.01) increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer.

Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma

Defects in the DNA damage repair pathway contribute to cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER). Although BER pathway genes (OGG1, APEX1 and XRCC1) have been investigated in a number of cancers, our knowledge on the prognostic significance of these genes and their role in head and neck squamous cell carcinoma is limited. Protein levels of OGG1, APEX1 and XRCC1 and a proliferation marker, Ki-67, were examined by immunohistochemical analysis, in a cohort of 50 HNSCC patients. Significant downregulation of OGG1 (p < 0.04) and XRCC1 (p < 0.05) was observed in poorly differentiated HNSCC compared to mod–well-differentiated cases. Significant upregulation of APEX1 (p < 0.05) and Ki-67 (p < 0.05) was observed in poorly differentiated HNSCC compared to mod-well-differentiated cases. Significant correlation was observed between XRCC1 and OGG1 (r = 0.33, p < 0.02). Inverse correlations were observed between OGG1 and Ki-67 (r = −0.377, p < 0.005), between APEX1 and XRCC1 (r = −0.435,p < 0.002) and between OGG1 and APEX1 (r = −0.34, p < 0.02) in HNSCC. To confirm our observations, we examined BER pathway genes and a proliferation marker, Ki-67, expression at the mRNA level on 50 head and neck squamous cell carcinoma (HNSCC) and 50 normal control samples by quantitative real-time polymerase chain reaction. Significant downregulation was observed in case of OGG1 (p < 0.04) and XRCC1 (p < 0.02), while significant upregulation was observed in case of APEX1 (p < 0.01) and Ki-67 (p < 0.03) in HNSCC tissue samples compared to controls. Our data suggested that deregulation of base excision repair pathway genes, such as OGG1, APEX1 and XRCC1, combined with overexpression of Ki-67, a marker for excessive proliferation, may contribute to progression of HNSCC in Pakistani population.

Magic Labelings of Type (a, b, c) of Families of Wheels

In this paper, firstly, we study magic labeling of type (1, 1, 1) for wheels and subdivided wheels. Secondly, we prove that a wheel admits a magic labeling of type (0, 1, 1). We also prove that any odd wheel admits a magic labeling of type (0, 1, 0). At the last, we find the magic labeling of type (1, 1, 0) for subdivided wheels.

On cycle-supermagicness of subdivided graphs

Llado and Moragas [‘Cycle-magic graphs’, Discrete Math. 307 (2007), 2925–2933] showed the cyclic-magic and cyclic-supermagic behaviour of several classes of connected graphs. They discussed cycle-magic labellings of subdivided wheels and friendship graphs, but there are no further results on cycle-magic labellings of other families of subdivided graphs. In this paper, we find cycle-magic labellings for subdivided graphs. We show that if a graph has a cycle-(super)magic labelling, then its uniform subdivided graph also has a cycle-(super)magic labelling. We also discuss some cycle-supermagic labellings for nonuniform subdivided fans and triangular ladders.