School Of Health Sciences

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Author: search.filters.author.Kumar, RajHas 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 Verlag, 2018) Kalra, Sourav; Kaur, Raman Preet; Ludhiadch, Abhilash; Shafi, Gowhar; Vashista, Rajesh; Kumar, Raj; Munshi, Anjana
    Purpose: 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. Methods: A total of 250 confirmed breast cancer patients were involved in the study. Genotyping was performed on an Illumina Infinium HD assay platform using a Global Screening Array (GSA) microchip. GenomeStudio (Illumina, Inc.) was used for data preprocessing and a p value less than or equal to 5 ? 10?8 was considered statistically significant. To rule out the influence of confounding risk factors, a step-wise multivariate regression analysis was carried out to evaluate the association of genotype with overall clinical outcome. Results: Two gene variants, CYP2C19 (G681A) and ALDH1A1*2 (17 bp deletion), were found to be significantly associated with the disease outcome, including overall survival, recurrence and metastasis, in breast cancer patients on adjuvant therapy. Both these genes are involved in the pharmacokinetics of cyclophosphamide. However, none of the variants in the genes involved in pharmacokinetics and pharmacodynamics of doxorubicin were found to have any significant impact on disease outcome in the studied group. Conclusion: CYP2C19 (G681A) variant and ALDH1A1*2 emerged as two important biomarkers associated with bad outcome in breast cancer patients on adjuvant therapy. ? 2018 Springer-Verlag GmbH Germany, part of Springer Nature
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    Editorial: Signal Transduction Inhibitors as Promising Anticancer Agents
    (Hindawi, 2015) Kumar, Raj; Santos, Cedric Dos; Ahluwalia, Tarunveer Singh; Singh, Sandeep
    Cancer is a group of diseases sharing common features like unrestrictive growth, metastasis, and angiogenesis; however the basic signal transduction pathways are deregulated to such an extent that every cancer case itself poses new challenges for the therapeutics. Worldwide approximately 7.6 million people died of cancer in year 2008 and it has been projected that 13.1 million deaths will be due to cancer by year 2030. Understanding the disease etiology and dysregulation of tissue microenvironment, signal transduction pathways are the potential directions, which may help us find the possible cure for the disease. However, recent advances in cancer therapeutics are proving to be beneficial for the patients but there is still a lot to be desired. Continuous research worldwide is focusing on developing better therapeutics as well as finding novel druggable targets for better efficacy. Another recent development is novel multitarget drugs, which may increase the efficacy manyfold.
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    Structural insights of cyclin dependent kinases: Implications in design of selective inhibitors
    (Elsevier Masson SAS, 2017) Kalra, Sourav; Joshi, Gaurav; Munshi, Anjana; Kumar, Raj
    There are around 20 Cyclin-dependent kinases (CDKs) known till date, and various research groups have reported their role in different types of cancer. The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. The revolutionary outcome of palbociclib in 2015 as CDK4/6 inhibitor added a new charm to the specific inhibitor design for CDKs. Computer-aided drug design (CADD) tools added a benefit to the design and development of new CDK inhibitors by studying the binding pattern of the inhibitors to the ATP binding domain of CDKs. Herein, we have attempted a comparative analysis of structural differences between several CDKs ATP binding sites and their inhibitor specificity by depicting the important ligand-receptor interactions for a particular CDK to be targeted. This perspective provides futuristic implications in the design of inhibitors considering the spatial features and structural insights of the specific CDK. ? 2017 Elsevier Masson SAS