Browsing by Author "Waseem, Mohammad"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India
    (Sage, 2016) Waseem, Mohammad; Hussain, Syed Rizwan; Kumar, Shashank; Serajuddin, Mohammad; Mahdi, Farzana; Sonkar, Satyendra Kumar; Bansal, Chery; Ahmad, Mohammad Kaleem
    Background Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. Materials and Methods Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. Results The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P= 0.007 and P = 0.005, respectively) between the control and the case subjects. Conclusion This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women.
  • Thumbnail Image
    Item
    D Allele Frequency in Insertion/Deletion Polymorphism of the Angiotensin Converting Enzyme (ACE) Gene is Associated with Development of Breast Cancer Risk in Indian Women
    (Bentham Science, 2016) Kumar, Shashank; Hussain, Syed Rizwan; Waseem, Mohammad; Mahdi, Farzana; Bansal, Chery; Ahmad, Mohammad Kaleem
    Aims: Breast cancer is the second most common cancer in the world and, by far, the most frequent cancer among women. Scientific literature has hypothesized the association of ACE I/D polymorphism with breast cancer for several decades. Unfortunately the outcomes of studies are inconsistent. Thus the present study was designed to evaluate the association of ACE gene (I/D) polymorphism with breast cancer in Indian population. Methods: Genotyping was performed by PCR (polymerase chain reaction), using genomic DNA extracted from peripheral blood of subjects, with (213 cases) or without (213 controls) breast cancer. Findings: The distribution of ACE genotype frequencies i.e. II, DD and ID in patients was 43.19%, 16.43% and 40.38% respectively. In healthy control group II, DD and ID frequencies were 52.58%, 11.27% and 36.15% respectively. The frequencies of D and I alleles were 29.34% and 70.66% in the healthy subjects, while 36.62% and 63.38% among the patient group. Frequency of D allele was significantly different (p=0.0287) between control and case subjects. Significance: The present study showed an association of D allele of ACE gene with increased genetic risk factor for breast cancer in Indian women. 0.2% increased disease risk was found in patients carrying D allele.
  • No Thumbnail Available
    Item
    Identification of miRNAs and related hub genes associated with the triple negative breast cancer using integrated bioinformatics analysis and in vitro approach
    (Taylor and Francis Ltd., 2021-08-13T00:00:00) Shuaib, Mohd; Prajapati, Kumari Sunita; Singh, Atul Kumar; Kushwaha, Prem Prakash; Waseem, Mohammad; Kumar, Shashank
    Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype generally associated with younger women. Due to the lack of suitable drugable targets in TNBC, the microRNAs are considered as a better hope as therapeutic agents for the management of the disease. In this study, we identified differentially expressed miRNAs (DEMs) and associated hub genes in TNBC microarray data (GSE38167, GSE60714, and GSE10833) using bioinformatics tools. The identified miRNAs and genes were validated in the TNBC cell line model (MDA-MB-231) compared with the normal breast cells (MCF-10A) using the qRT-PCR technique. False-positive DEMs were avoided by comparing the DEMs profile of TNBC and triple positive breast cancer (TPBC) cell line model (BT474) compared with the MCF-10A cells data. In addition, we studied the effect of anticancer phytochemicals on the differential expression of miRNAs and genes in MDA-MB-231 cells. Furthermore, target predictions, functional enrichment and KEGG pathway analysis, mutation and copy number alterations, and overall survival analysis of DEMs in TNBC sample was investigated using standard computational tools. The study identifies first time the association of hsa-miR-1250, has-miR-1273, and has-miR-635 with the TNBC. DEMs showed significant association with the Wnt, ErbB, PI3-Akt and cAMP signaling pathways having clinical implications in TNBC tumorigenesis. The DEMs and hub genes (HOXC6 and ACVR2B) showed survival disadvantages in TNBC patients. In summary, the identified miRNAs and hub genes show important implications in TNBC tumorigenesis and patient survival. We recommend further experimental studies on pathophysiological mechanism of the identified miRNAs and hub genes in TNBC. Communicated by Ramaswamy H. Sarma. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
  • No Thumbnail Available
    Item
    Withania somnifera phytochemicals possess SARS-CoV-2 RdRp and human TMPRSS2 protein binding potential
    (Springer, 2022-06-15T00:00:00) Prajapati, Kumari Sunita; Singh, Atul Kumar; Kushwaha, Prem Prakash; Shuaib, Mohd; Maurya, Santosh Kumar; Gupta, Sanjay; Senapati, Sabyasachi; Singh, Surya Pratap; Waseem, Mohammad; Kumar, Shashank
    Abstract: Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has infected approximately 26�million people and caused more than 6�million deaths globally. Spike (S)-protein on the outer surface of the virus uses human trans-membrane serine protease-2 (TMPRSS2) to gain entry into the cell. Recent reports indicate that human dipeptidyl peptidase-4 inhibitors (DPP4 or CD26) could also be utilized to check the S-protein mediated viral entry into COVID-19 patients. RNA dependent RNA polymerase (RdRp) is another key virulence protein of SARS-CoV-2 life cycle. The study aimed to identify the potential anti-SARS-CoV-2 inhibitors present in Withania somnifera (Solanaceae) using computer aided drug discovery approach. Molecular docking results showed that flavone glycoside, sugar alcohol, and flavonoid present in W. somnifera showed ? 11.69, ? 11.61, ? 10.1, ? 7.71�kcal/mole binding potential against S-protein, CD26, RdRp, and TMPRSS2 proteins. The major standard inhibitors of the targeted proteins (Sitagliptin, VE607, Camostat mesylate, and Remdesivir) showed the ? 7.181, ? 6.6, ? 5.146, and ? 7.56�kcal/mole binding potential. Furthermore, the lead phytochemicals and standard inhibitors bound and non-bound RdRp and TMPRSS2 proteins were subjected to molecular dynamics (MD) simulation to study the complex stability and change in protein conformation. The result showed energetically favorable and stable complex formation in terms of RMSD, RMSF, SASA, Rg, and hydrogen bond formation. Drug likeness and physiochemical properties of the test compounds exhibited satisfactory results. Taken together, the present study suggests the presence of potential anti-SARS-CoV-2 phytochemicals in W. somnifera that requires further validation in in vitro and in vivo studies. Graphical Abstract: [Figure not available: see fulltext.] � 2022, The Author(s) under exclusive licence to Society for Plant Research.