School Of Basic And Applied Sciences
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Item Evaluation of mean platelet volume and platelet count in ischemic stroke and its subtypes: focus on degree of disability and thrombus formation(Taylor and Francis Ltd., 2022-08-27T00:00:00) Ludhiadch, Abhilash; Yadav, Pooja; Singh, Sunil Kumar; Sulena; Munshi, AnjanaBackground: Platelets are crucial players in thrombus formation during ischemic stroke. Platelet (PLT) count and Mean platelet volume (MPV) are important parameters that affect platelet functions. The current study has been carried out with an aim to evaluate the association of MPV and PLT count with ischemic stroke in a population from the Malwa region of Punjab. Material and Methods: The study included one hundred and fifty ischemic stroke patients. The extent of disability occurs by stroke was measured by mRS. MPV and PLT was evaluated using cell counter. Further, PLT count was confirmed in 50% of patients using flow cytometer. Clot formation rate was evaluated using Sonoclot Coagulation and Platelet Function Analyzer. All the statistical analysis was carried out using SPSS. Results: A significant association of increased MPV (p < 0.02) was found with the ischemic stroke. However, PLT count did not show a significant association with the disease (p < 0.07). Further, a stepwise multiple logistic regression (MLR) analysis controlling the other confounding risk factors evaluated the association of hypertension and MPV with the disease. Patients with higher mRS were found to have high MPV values confirming that higher MPV is correlated with disability occurs by ischemic stroke. MPV was also found to be significantly associated with large artery atherosclerosis (p < 0.001). Clot formation analysis revealed that ischemic stroke patients bear higher clot rate (CR) and Platelet function (PF) values. Conclusions: Elevated MPV is an independent risk factor for Ischemic stroke along with hypertension. In addition, higher MPV associated significantly with stroke disability as well. � 2022 Informa UK Limited, trading as Taylor & Francis Group.Item Trehalose and its Diverse Biological Potential(Bentham Science Publishers, 2023-06-07T00:00:00) Sharma, Eva; Shruti, P.S.; Singh, Shagun; Singh, Tashvinder; Kaur, Prabhsimran; Jodha, Bhavana; Srivastava, Yashi; Munshi, Anjana; Singh, SandeepTrehalose, a disaccharide molecule of natural origin, is known for its diverse biological ap-plications, like in drug development, research application, natural scaffold, stem cell preservation, food, and various other industries. This review has discussed one such diverse molecule �trehalose aka mycose�, and its diverse biological applications with respect to therapeutics. Due to its inertness and higher stability at variable temperatures, it has been developed as a preservative to store stem cells, and later, it has been found to have anticancer properties. Trehalose has recently been associated with modulating cancer cell metabolism, diverse molecular processes, neuroprotective effect, and so on. This article describes the development of trehalose as a cryoprotectant and protein stabilizer as well as a dietary component and therapeutic agent against various diseases. The article discusses its role in diseases via modulation of autophagy, various anticancer pathways, metabolism, inflammation, aging and oxidative stress, cancer metastasis and apoptosis, thus highlighting its diverse biological potential. � 2023 Bentham Science Publishers.Item Trehalose and its Diverse Biological Potential(Bentham Science Publishers, 2023-06-07T00:00:00) Sharma, Eva; Shruti, P.S.; Singh, Shagun; Singh, Tashvinder; Kaur, Prabhsimran; Jodha, Bhavana; Srivastava, Yashi; Munshi, Anjana; Singh, SandeepTrehalose, a disaccharide molecule of natural origin, is known for its diverse biological ap-plications, like in drug development, research application, natural scaffold, stem cell preservation, food, and various other industries. This review has discussed one such diverse molecule �trehalose aka mycose�, and its diverse biological applications with respect to therapeutics. Due to its inertness and higher stability at variable temperatures, it has been developed as a preservative to store stem cells, and later, it has been found to have anticancer properties. Trehalose has recently been associated with modulating cancer cell metabolism, diverse molecular processes, neuroprotective effect, and so on. This article describes the development of trehalose as a cryoprotectant and protein stabilizer as well as a dietary component and therapeutic agent against various diseases. The article discusses its role in diseases via modulation of autophagy, various anticancer pathways, metabolism, inflammation, aging and oxidative stress, cancer metastasis and apoptosis, thus highlighting its diverse biological potential. � 2023 Bentham Science Publishers.Item Genomic alterations associated with HER2+ breast cancer risk and clinical outcome in response to trastuzumab(Springer, 2019) Singla, H; Kaur, R.P; Shafi, G; Vashistha, R; Banipal, R.P.S; Kumar, Vinod; Munshi, AnjanaHuman epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC) is an aggressive BC subtype characterized by HER2 overexpression/amplification. Genomic alterations of HER2 and others have been reported to be associated with, HER2 overexpression and prediction of trastuzumab-response. Here, we aimed at identifying germline and somatic alterations associated with HER2+ BC and evaluating their association with clinical outcome in response to trastuzumab therapy given to HER2+ BC patients. Global Sequencing Array (GSA) and polymerase chain reaction-restriction length polymorphism (PCR-RFLP) techniques were used to determine alterations in HER2 and other HER2-interacting as well as signaling-related genes in HER2+ BC. In addition, 20 formalin fixed paraffin-embedded tissue samples were also evaluated by GSA for identifying significant variations associated with HER + BC as well as response to trastuzumab therapy. A germline variant in HER2 (I655V) was found to be significantly associated with the risk of the disease (p < 0.01). A nonsense mutation in PTPN11 (K99X), a pathogenic CCND1 splice site variant (P241P), a hotspot missense mutation in PIK3CA (E542K) and a hotspot missense mutation in TP53 (R249S); were observed in 25%, 75%, 30% and 40% of the HER2+ BC tissue samples, respectively. Mutant CCND1 (P241P) and PIK3CA (E542K) were found to be significantly associated with reduced disease-free survival (DFS) in patients treated with trastuzumab (p: 0.018 and 0.005, respectively). These results indicate that HER2, PTPN11, CCND1 and PIK3CA genes are important biomarkers in HER2+ BC. Moreover, the patients harboring mutant CCND1 and PIK3CA exhibit a poorer clinical outcome as compared to those carrying wild-type CCND1 and PIK3CA. © 2018, Springer Nature B.V.Item 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, AnjanaCyclophosphamide 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.Item PPInS: a repository of protein-protein interaction sitesbase(Nature Publishing Group, 2018) Kumar V.; Mahato S.; Munshi, Anjana; Kulharia, MaheshProtein-Protein Interaction Sitesbase (PPInS), a high-performance database of protein-protein interacting interfaces, is presented. The atomic level information of the molecular interaction happening amongst various protein chains in protein-protein complexes (as reported in the Protein Data Bank [PDB]) together with their evolutionary information in Structural Classification of Proteins (SCOPe release 2.06), is made available in PPInS. Total 32468 PDB files representing X-ray crystallized multimeric protein-protein complexes with structural resolution better than 2.5 Å had been shortlisted to demarcate the protein-protein interaction interfaces (PPIIs). A total of 111857 PPIIs with ~32.24 million atomic contact pairs (ACPs) were generated and made available on a web server for on-site analysis and downloading purpose. All these PPIIs and protein-protein interacting patches (PPIPs) involved in them, were also analyzed in terms of a number of residues contributing in patch formation, their hydrophobic nature, amount of surface area they contributed in binding, and their homo and heterodimeric nature, to describe the diversity of information covered in PPInS. It was observed that 42.37% of total PPIPs were made up of 6-20 interacting residues, 53.08% PPIPs had interface area ?1000 Å 2 in PPII formation, 82.64% PPIPs were reported with hydrophobicity score of ?10, and 73.26% PPIPs were homologous to each other with the sequence similarity score ranging from 75-100%. A subset ''Non-Redundant Database (NRDB)'' of the PPInS containing 2265 PPIIs, with over 1.8 million ACPs corresponding to the 1931 protein-protein complexes (PDBs), was also designed by removing structural redundancies at the level of SCOP superfamily (SCOP release 1.75). The web interface of the PPInS (http://www.cup.edu.in:99/ppins/home.php) offers an easy-to-navigate, intuitive and user-friendly environment, and can be accessed by providing PDB ID, SCOP superfamily ID, and protein sequence. - 2018, The Author(s).Item Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome(Mosby Inc., 2018) Kaur, R.P.; Rubal, Banipal,; Vashistha, R.; Dhiman, Monisha; Munshi, AnjanaBackground and Purpose: Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared. Material and Methods: Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients. Results: Elevated levels of CRP were found among the diseased in comparison with controls (P < 0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)]. Conclusion: Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high. ? 2018Item 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, AnjanaBackground: 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.Item 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, RajStructure-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.