School Of Basic And Applied Sciences

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Author: search.filters.author.Kalra, SouravHas files: Yes

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    Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array.
    (Springer, 2018) Kalra, Sourav; Ludhiadch Abhilash; Shafi, Gowhar; Vashista, Rajesh; Kumar, Raj; Munshi, Anjana
    Cyclophosphamide and doxorubicin (adjuvant chemotherapy) are commonly used to treat breast cancer patients. Variation in the genes involved in pharmacodynamics and pharmacokinetics of these drugs plays an important role in prediction of drug response and survival. The present study was carried out with an aim to evaluate the variation in all the genes involved in pharmacokinetic and pharmacodynamics pathways of cyclophosphamide and doxorubicin, and correlate specific variants with disease outcome in breast cancer patients from the Malwa region of Punjab.
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    Role of genomic alterations in HER2 positive breast carcinoma: Focus on susceptibility and trastuzumab-therapy
    (Bentham Science Publishers B.V., 2017) Singla, Heena; Kalra, Sourav; Kheterpal, Preeti; Kumar, Vinod; Munshi, Anjana
    Background: Breast cancer is the most frequently diagnosed life-threatening malignancy among women, across the globe. HER2 positive is a distinct breast cancer subtype, on account of its unique biology and physiological behavior. Results: Amplification of HER2 oncogene/polysomy 17 leads to HER2 overexpression that is a significant causal implication in HER2 positive breast cancer. HER2 gene variants, as well as other genes/gene variants, are involved in its overexpression, disease prognosis and in predicting the susceptibility towards HER2 positive breast cancer. Trastuzumab (Herceptin) is the most commonly used therapy for treating patients with HER2 positive status. Genomic alterations are incriminated in the development of trastuzumab-resistance, which influences the response towards trastuzumab-therapy. Conclusion: In the current review article, we have summarized the genomic alterations that are responsible for overexpression of HER2 and therefore, increased risk of breast cancer. In addition, the gene variants affecting response towards trastuzumab-therapy have also been discussed. ? 2017 Bentham Science Publishers.
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    Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases
    (John Wiley and Sons Inc., 2018) Kumar, Raj; Joshi, Gaurav; Kler, Harveen; Kalra, Sourav; Kaur, Manpreet; Arya, Ramandeep
    Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases? binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes. ? 2017 Wiley Periodicals, Inc.
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    Pyrimidine containing epidermal growth factor receptor kinase inhibitors: Synthesis and biological evaluation
    (Blackwell Publishing Ltd, 2017) Joshi, Gaurav; Nayyar, Himanshu; Kalra, Sourav; Sharma, Praveen; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
    Structure-based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a?d are reported. The compounds (1a?d) inhibited the EGFR kinase activity in vitro with IC50 range 740?nm to 3??m. mRNA expression of EGFR downstream target genes, that is twist, c-fos and aurora were found to be altered upon treatment with compounds 1a?d. The compounds 1a?d exhibited excellent anticancer activity at low micromolar level (3.2?9??m) in lung, colon and breast cancer cell lines. Furthermore, compounds induced the alteration in mitochondrial membrane potential and reactive oxygen species level and. Selected compound 1b was found to increase sub-G1 population indicative of cell death, the mode of cell death was apoptotic as evident from Annexin V verses propidium iodide assay. Molecular modelling further helped to investigate the binding recognition pattern of the compounds in ATP binding EGFR domain similar to erlotinib and dissimilar to WZ4002. ? 2017 John Wiley & Sons A/S.