Browsing by Author "Singh, Sandeep"

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1-Acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles: Exhibiting anticancer activity through intracellular ROS scavenging and the mitochondria-dependent death pathway
(Wiley-VCH Verlag, 2014) Alex, Jimi M.; Singh, Sandeep; Kumar, Raj
A series of 17 analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1 to JP-17) bearing two aromatic rings at positions 3 and 5, either of which ought to be heterocyclic, were synthesized and evaluated for their anti-proliferative potential against breast cancer (MCF-7 and T-47D) and lung cancer (H-460 and A-549) cell lines for the first time. JP-1-7, -10, -11, -14, and -15 were observed to exhibit significant anti-proliferative activity against MCF-7 cells. Some notions about structure-activity relationships are reported. The investigated compounds were found to lower the intracellular reactive oxygen species in the H2DCFDA assay and also caused mitochondria-dependent cell death in the MCF-7 cell line, indicating a plausible mechanism of their anticancer effect. Analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1-17) were synthesized and evaluated for their anti-proliferative activity in four cancer cell lines and for their intracellular ROS scavenging properties. An attempt was made to determine the mitochondrial membrane potential of MCF-7 cells treated with JP-1 and -14, aiming to elucidate the mechanism by which proliferation was curbed. ? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Analyzing GAVI the Vaccine Alliance as a Global Health Partnership Model: A Constructivist Analysis of the Global Health Crisis
(SAGE Publications Ltd, 2022-09-06T00:00:00) Singh, Sandeep; Bawa, Jagmeet; Singh, Bawa; Singh, Balinder; Bika, Shankar Lal
The ongoing debate on the conceptual underpinnings of constructivism and global health partnerships (GHPs) in global health studies has a dimension that deserves closer attention. This paper attempts to draw attention to a few aspects of the debate using Finnemore�s constructivist analysis. According to this study, global actors need to rethink their paradoxical notions of pandemic crisis survival in light of the growing demand for mobilizing diverse global health agents and the necessity of constructing complex GHPs to address challenges of international significance. A global response based on solidarity and multilateralism is the only way to effectively combat this pandemic. Against this backdrop, the article analyses this development through an ideational ontological case study of the GAVI, the Vaccine Alliance. This article contributes to the debate by explaining how the GAVI Alliance fostered global collaboration and can serve as a template for future GHPs. � 2022 Association of Asia Scholars.
Caulerpa taxifolia inhibits cell proliferation and induces oxidative stress in breast cancer cells
(Springer, 2018) Mehra, Richa; Bhushan, Satej; Yadav, Umesh Prasad; Bast, Felix; Singh, Sandeep
Caulerpa taxifolia (M. Vahl) C. Agardh or killer alga is known to possess several bioactive secondary metabolites with unique structural modifications. We investigated anti-oxidant and anti-proliferative activity of C. taxifolia extract (CTE) on breast and lung cancer cells, along with possible effects on mitochondrial membrane potential (MMP) and cell cycle progression. The results revealed up to 6-folds increase in reactive oxygen species (ROS), 2-folds increase in glutathione reductase (GR) activity, 1.7-fold increase in superoxide dismutase (SOD) activity and 1.8-fold change in catalase activity w.r.t. untreated cells i.e. 10.72 to 21.44 nmol/min/mL, 2.0 to 3.49 U/mL and 37.51 to 69.26 U/min/g FW, respectively, in MDA-MB-cells. Likewise, selective anti-proliferative activity with IC50 0.19 + 0.1, 0.27 + 0.1, and 0.43 + 0.1 μg/μL, was recorded in MDA-MB-231, T-47D, and H1299 cells. In addition, dose-dependent increase in MMP of up to 40% and G1/S phase mitotic arrest was documented by CTE treatment in MDA-MB-231 cells. The results suggest an anti-proliferative and oxidative stress inducing activity of CTE. Changes in MMP and cell cycle arrest further support the anti-cancer effects of CTE. It is believed that C. taxifolia may be considered as a potent source of anti-cancer drugs, subject to further validations.
Chitosan centered bionanocomposites for medical specialty and curative applications: A review
(Elsevier B.V., 2017) Ahmad, Mudasir; Manzoor, Kaiser; Singh, Sandeep; Ikram, Saiqa
The polyfunctional nature of chitosan enables its application not only in polymer technology but also shows their importance in the field of nanotechnology for the fabrication of the wide spectrum of functional nanomaterials in biomedical field. Chitosan is a poly aminosaccharide with appealing structure composed of ?-(1???4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It has various functional groups that enriches for various properties such as antibacterial, mucoadhasive, nontoxic, biodegradable, biocompatible. With the advancement of material technologies, chitosan is being chemically modified into self-assembled nanocomposites for advanced biomedical applications. This review article demonstrate the various schemes for the preparation of chitosan nanocomposites from different functional material, focusing on their application specifically in tissue engineering, drug and gene delivery, wound healing and bioimaging. ? 2017 Elsevier B.V.
Comprehensive analysis of culture conditions governing differentiation of MSCs into articular chondrocytes
(Newlands Press Ltd, 2023-05-18T00:00:00) Singh, Harsh Vikram; Das, Lakshmana; Malayil, Rhuthuparna; Singh, Tashvinder; Singh, Sandeep; Goyal, Tarun; Munshi, Anjana
Treatment of osteoarthritic patients requires the development of morphologically and mechanically complex hyaline cartilage at the injury site. A tissue engineering approach toward differentiating mesenchymal stem cells into articular chondrocytes has been developed to overcome the drawbacks of conventional therapeutic and surgical procedures. To imitate the native micro and macro environment of articular chondrocytes, cell culture parameters such as oxygen concentration, mechanical stress, scaffold design, and growth factor signalling cascade regulation must be addressed. This review aims to illuminate the path toward developing tissue engineering approaches, accommodating these various parameters and the role these parameters play in regulating chondrogenesis for better articular cartilage development to treat osteoarthritis effectively. � 2023 Future Medicine Ltd.
Conflict and social determinants of health: would global health diplomacy resolve the Afghanistan healthcare conundrum?
(Routledge, 2023-06-21T00:00:00) Singh, Bawa; Singh, Sandeep; Kaur, Jaspal; Singh, Kulwinder; Popalzay, Abdul Wasi
Public health, conflict/war, Social Determinants of Health (SDHs) and Global Health Diplomacy (GHD) are believed to be strongly interwoven. Afghanistan that is known as the �Graveyard of the Empire� has been passing through a very critical phase given the prolonged civil war during the last couple of decades, wherein the ongoing current situation further pushed the country towards the collapse of the political and economic systems. Thereby, Afghanistan�s healthcare system has been entrapped into the civil war conundrum causing the SDHs to be seriously affected. Conflict in any form, i.e. local, regional, or international, has left black swan impacts on not only the SDHs but also led to health crises given the inaccessibility, unaffordability, and more of lack of the infrastructure, and exodus of trained medical staff and healthcare inequity. In this situation, it is anticipated that GHD could play a significant role in providing equitable healthcare to people at stake. Against this backdrop, the focus of this paper is; how the SDHs have been impacted by the civil conflict and how the public healthcare has been turned into a conundrum; would the GHD resolve the healthcare crisis in the prevailing scenario?. � 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Connecting for energy? india's negotiation for space in central asia
(Central University of Punjab, 2014) Singh, Sandeep; Varghese, V. J
The present research aims to examine the role of energy demands in determining the contours of India's new 'Connect Central Asia' policy. In a world of accelerating energy needs, possession and non-possession of energy sources are determining factors of the global economy of energy with significant impact on international relations and global peace. According to Exxon Mobil World Energy Outlook 2013 the world's population will rise by more than 25 percent from 2010 to 2040 which means growing mobility requirements and energy demand. The rising living standards of the people will also impacts energy demands. These dynamic changes demand understanding of political economy of global energy crisis as a whole and how it has become a strong factor in foreign policy initiatives. The plan of the present research is to contextualise India's energy crisis in the political economy of global energy crisis and investigate how far it is factored in its new found interest in Central Asian countries. Though, India accounts 2.49 per cent of world's annual energy production, its consumption accounts for 3.45 per cent of the global consumption. Its increasing population and enormous growth of middle class is posing a challenge to India in this regard. The research presumes that due to the insecure and unstable supply from the Middle East, India's 'Connect Central Asia' policy has a strong energy angle factored into it.
Covid-19 pandemic and reimagination of multilateralism through global health diplomacy
(MDPI, 2021-10-21T00:00:00) Gupta, Nippun; Singh, Bawa; Kaur, Jaspal; Singh, Sandeep; Chattu, Vijay Kumar
The ongoing pandemic COVID-19 has made it very clear that no one is safe until everyone is safe. But how can everyone be safe when the pandemic has broken every nerve of the economy and put an extra burden on the already crippled healthcare systems in low-income countries? Thus, the pandemic has changed the orientation of domestic as well as global politics, with many geopolitical shifts. The exponential growing infected cases and more than four million deaths has demanded a global response in terms of multilateralism. However, declining multilateralism and the need for its reforms was a much-delayed response. Given this context, this paper aimed to link the decline of multilateralism in the face of the pandemic by highlighting various instances of its failure and success; and highlighting the need for its revival. The article critically examines and evaluates the responses of multilateralism and global health diplomacy (GHD) during the pandemic. The ongoing black swan kind of event (an unexpected event) has obligated global leadership to think in terms of the revival of multilateralism through GHD. Historically, multilateralism through GHD has been shown to play an important role in managing and combating pandemics. The article further discusses various theoretical aspects such as sovereignty and hegemonic stability theory as reasons for the failing of multilateralism. The paper concludes by emphasizing the importance of foresight in reviving multilateralism in the pursuit of a more sustainable future. � 2021 by the authors. Licensee MDPI, Basel, Switzerland.
CYP/PON genetic variations as determinant of organophosphate pesticides toxicity
(Springer India, 2017) Kaur, GURPREET; Jain, A.K.; Singh, Sandeep
In the present scenario of increased accumulation of pesticides in the environment, it is important to understand its impact on human health. The focus is on gene?environment interaction, highlighting the consequences and factors that may halt the biotransformation of some pesticides and change their actual dose response curve due to mixed exposure to pesticides. The paraoxonase and cytochrome P450 gene families are involved in the metabolism of oxon derivate (toxic than its parent compound) of organophosphate pesticides, thus, mutations in these genes may impact the metabolic outcome of pesticides and subsequent health hazards. The complex multi gene?environment interaction and one gene ? one risk factor are two different aspects to understand the potential health effect related to environmental exposure studies. The genetic polymorphisms are associated with varying levels of risk within the population, as gene products of varied genotype alter the biotransformation of exogenous/endogenous substrates. This paper is aimed to review the impact of endogenous and exogenous factors on a mechanistic pathway of organophosphate pesticide biotransformation and various risk associated with it among the human population. Understanding the genetic polymorphism of genes involved in pesticide metabolism and highlighting the gene isoform dependent interindividual differences to metabolize particular pesticides may help us to unravel the reasons behind differential toxicity for pesticides exposure than expected. ? 2017, Indian Academy of Sciences.
Design and synthesis of non-covalent imidazo[1,2-a]quinoxaline-based inhibitors of EGFR and their anti-cancer assessment
(MDPI AG, 2021-03-09T00:00:00) Kumar, Manvendra; Joshi, Gaurav; Arora, Sahil; Singh, Tashvinder; Biswas, Sajal; Sharma, Nisha; Bhat, Zahid Rafiq; Tikoo, Kulbhushan; Singh, Sandeep; Kumar, Raj
A series of 30 non-covalent imidazo[1,2-a]quinoxaline-based inhibitors of epidermal growth factor receptor (EGFR) were designed and synthesized. EGFR inhibitory assessment (against wild type) data of compounds revealed 6b, 7h, 7j, 9a and 9c as potent EGFRWT inhibitors with IC50 values of 211.22, 222.21, 193.18, 223.32 and 221.53 nM, respectively, which were comparable to erlotinib (221.03 nM), a positive control. Furthermore, compounds exhibited excellent antiproliferative activity when tested against cancer cell lines harboring EGFRWT; A549, a non-small cell lung cancer (NSCLC), HCT-116 (colon), MDA-MB-231 (breast) and gefitinib-resistant NSCLC cell line H1975 harboring EGFRL858R/T790M. In particular, compound 6b demonstrated significant inhibitory potential against gefitinib-resistant H1975 cells (IC50 = 3.65 �M) as compared to gefitinib (IC50 > 20 �M). Moreover, molecular docking disclosed the binding mode of the 6b to the domain of EGFR (wild type and mutant type), indicating the basis of inhibition. Furthermore, its effects on redox modulation, mitochondrial membrane potential, cell cycle analysis and cell death mode in A549 lung cancer cells were also reported. Copyright: � 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Design, microwave-mediated synthesis and biological evaluation of novel 4 aryl(alkyl)amino-3-nitroquinoline and 2,4-diaryl(dialkyl) amino-3-nitroquinolines as anticancer agents
(Elsevier, 2015) Chauhan, Monika; Rana, Anil; Alex, Jimi Marin; Negi, Arvind; Singh, Sandeep; Kumar, Raj
Design, microwave-assisted synthesis of novel 4-aryl (alkyl)amino-3-nitroquinoline (1a–1l) and 2,4-diaryl (dialkyl)amino-3-nitroquinolines (2a–2k and 3a) via regioselective and complete nucleophilic substitution of 2,4-dichloro-3-nitroquinoline, respectively in water are presented. The newly synthesized compounds were evaluated for the first time for antiproliferative activity against EGFR overexpressing human lung (A-549 and H-460) and colon (HCT-116-wild type and HCT-116-p53 null) cancer cell lines. Some notions about structure–activity relationships (SAR) are presented. Compounds 2e, 2f, 2j and 3a overall exhibited excellent anticancer activity comparable to erlotinib which was used as a positive control. Molecular modeling studies disclosed the recognition pattern of the compounds and also supported the observed SAR.
Design, synthesis and anticancer activity of 2-arylimidazo[1,2-a]pyridinyl-3-amines
(Academic Press Inc., 2021-11-01T00:00:00) Yadav, Umesh Prasad; Ansari, Arshad J.; Arora, Sahil; Joshi, Gaurav; Singh, Tashvinder; Kaur, Harsimrat; Dogra, Nilambra; Kumar, Raj; Kumar, Santosh; Sawant, Devesh M.; Singh, Sandeep
A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC50 values ranging from 1 to 5.5 ?M. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In-vitro enzyme assay showed selective topoisomerase II? inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using overexpression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression. � 2021 Elsevier Inc.
Design, Synthesis and Biological Evaluation of New 5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles as Topoisomerase Inhibitors
(John Wiley and Sons Inc, 2021-07-09T00:00:00) Kaur, Manpreet; Mehta, Vikrant; Arora, Sahil; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles are designed as topoisomerase (Topo) inhibitors, synthesised and assessed for their anticancer properties against breast (MDA-MB-231 and MCF7), lung (A549), and colorectal (HCT116) cancer cell lines. All the compounds induced significant cytotoxicity at low micromolar concentration. The compound 5e exerted potential anticancer effects on breast cancer cell lines at a low micromolar level (IC50<2 ?M), and showed negligible toxicity towards normal cells. Compound 5 e reduced reactive oxygen species (ROS) level in breast cancer cells, altered mitochondrial membrane potential and induced the cell cycle arrest at the G2/M phase. This was accompanied by downregulation of oncogenic p-Akt and upregulation of p-PTEN along with modulation of apoptotic markers suggesting multiple mechanisms to reduce cancer cell viability. Finally, the topoisomerase inhibition assay revealed the inhibitory activity of 5 e against Topo I and Topo II. � 2021 Wiley-VCH GmbH.
Design, Synthesis, and Anticancer Evaluation of Hemithioindigos via Inhibition of Human Topoisomerases
(John Wiley and Sons Inc, 2023-11-06T00:00:00) Kaur, Manpreet; Suman, Prabhat; Arora, Sahil; Singh, Tashvinder; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
Hemithioindigos were designed as topoisomerase inhibitors, synthesized, and evaluated for their anticancer properties against lung (A549) and breast (MDA-MB-468 and MCF7) cancer cell lines. Among all the synthetics, three compounds exerted potential anticancer effects on A549 (lung) and MCF7 (breast) cancer cell lines at low micromolar concentrations. The results revealed that two of these compounds blocked the cancer cells at the G1/S phase, while the third compound showed moderate G2/M inhibition, leading to necrotic cell death. Finally, the topoisomerase inhibition assays revealed their potent Topo I/II inhibitory actions as one of the primary anticancer mechanisms. Molecular docking studies further corroborated these findings. � 2023 Wiley-VCH GmbH.
Design, synthesis, biological evaluation of 3,5-diaryl-4,5-dihydro-1H-pyrazole carbaldehydes as non-purine xanthine oxidase inhibitors: Tracing the anticancer mechanism via xanthine oxidase inhibition
(Academic Press Inc., 2021-01-07T00:00:00) Joshi, Gaurav; Sharma, Manisha; Kalra, Sourav; Gavande, Navnath S.; Singh, Sandeep; Kumar, Raj
Xanthine oxidase (XO) has been primarily targeted for the development of anti-hyperuriciemic /anti-gout agents as it catalyzes the conversion of xanthine and hypoxanthine into uric acid. XO overexpression in various cancer is very well correlated due to reactive oxygen species (ROS) production and metabolic activation of carcinogenic substances during the catalysis. Herein, we report the design and synthesis of a series of 3,5-diaryl-4,5-dihydro-1H-pyrazole carbaldehyde derivatives (2a-2x) as xanthine oxidase inhibitors (XOIs). A docking model was developed for the prediction of XO inhibitory activity of our novel compounds. Furthermore, our compounds anticancer activity results in low XO expression and XO-harboring cancer cells both in 2D and 3D-culture models are presented and discussed. Among the array of synthesized compounds, 2b and 2m emerged as potent XO inhibitors having IC50 values of 9.32 � 0.45 �M and 10.03 � 0.43 �M, respectively. Both compounds induced apoptosis, halted the cell cycle progression at the G1 phase, elevated ROS levels, altered mitochondrial membrane potential, and inhibited antioxidant enzymes. The levels of miRNA and expression of redox sensors in cells were also altered due to increase oxidative stress induced by our compounds. Compounds 2b and 2m hold a great promise for further development of XOIs for the treatment of XO-harboring tumors. � 2021 Elsevier Inc.
Dietary Patterns and Breast Cancer Risk: A Multi-Centre Case Control Study among North Indian Women
(mdpi, 2018) Shridhar, Krithiga; Singh, Gurpreet; Dey, Subhojit; Dhatt, Sarvdeep Singh; Gill, Jatinder Paul Singh; Goodman, Michael; Magsumbol, Melina Samar; Pearce, Neil; Singh, Sandeep; Singh, Archna; Singh, Preeti; Thakur, Jarnail Singh; Dhillon, Preet Kaur
Evidence from India, a country with unique and distinct food intake patterns often characterized by lifelong adherence, may offer important insight into the role of diet in breast cancer etiology. We evaluated the association between Indian dietary patterns and breast cancer risk in a multi-centre case-control study conducted in the North Indian states of Punjab and Haryana. Eligible cases were women 30–69 years of age, with newly diagnosed, biopsy-confirmed breast cancer recruited from hospitals or population-based cancer registries. Controls (hospital- or population-based) were frequency matched to the cases on age and region (Punjab or Haryana). Information about diet, lifestyle, reproductive and socio-demographic factors was collected using a structured interviewer-administered questionnaire. All participants were characterized as non-vegetarians, lacto-vegetarians (those who consumed no animal products except dairy) or lacto-ovo-vegetarians (persons whose diet also included eggs). The study population included 400 breast cancer cases and 354 controls. Most (62%) were lacto-ovo-vegetarians. Breast cancer risk was lower in lacto-ovo-vegetarians compared to both non-vegetarians and lacto-vegetarians with odds ratios (95% confidence intervals) of 0.6 (0.3–0.9) and 0.4 (0.3–0.7), respectively. The unexpected difference between lacto-ovo-vegetarian and lacto-vegetarian dietary patterns could be due to egg-consumption patterns which requires confirmation and further investigation.
Differential molecular mechanistic behavior of HDACs in cancer progression
(Springer, 2022-08-16T00:00:00) Singh, Tashvinder; Kaur, Prabhsimran; Singh, Paramdeep; Singh, Sandeep; Munshi, Anjana
Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs� role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Dual inhibitors of epidermal growth factor receptor and topoisomerase IIa derived from a quinoline scaffold
(Royal Society of Chemistry, 2016) Chauhan, Monika; Joshi, Gaurav; Kler, Harveen; Kashyap, Archana; Amrutkar, Suyog M.; Sharma, Praveen; Bhilare, Kiran D.; Banerjee, Uttam C.; Singh, Sandeep; Kumar, Raj
Based on the quinazoline bearing EGFR inhibitors, a series of thirty four compounds having a quinoline scaffold were synthesised and evaluated in vitro for EGFR kinase inhibitory activity. A structure-activity relationship study revealed that 2,4-bis(arylamino) substituted quinolines possessed better anti-EGFR kinase activity. Compounds 3f and 3m emerged as potent EGFR kinase inhibitors (200 and 210 nM, respectively) and showed excellent anticancer activity at the micromolar level against a panel of cancer cell lines comparable to erlotinib. Furthermore, representative compounds inhibited the human topoisomerase II? selectively and catalytically, did not intercalate with DNA, increased intracellular ROS concentration (except 3m) and altered the mitochondrial membrane potential of the cancer cells. Cell cycle analysis and annexin-V staining in a lung cancer cell line showed that the compounds delayed cell cycle progression by inducing cell cycle arrest and subsequent apoptosis at the G1 phase. The facts were further corroborated through molecular modeling studies. ? 2018 The Royal Society of Chemistry.
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.
Eradicating Cancer Stem Cells: Concepts, Issues, and Challenges
(Springer New York LLC, 2018) Kaur, Gurpreet; Sharma, Praveen; Dogra, Nilambra; Singh, Sandeep
The cells of malignant cancers result in the evolution of cells with stem-like characteristics, commonly known as cancer stem cells (CSCs). Progress of anticancer therapies is severely hampered because of disease relapse mostly in a more aggressive form due to CSCs. These CSCs are more or less like embryonic or tissue stem cells, known for their capacity of self-renewal, exactly recapitulate of the original tumor. Deregulation of key stem cell pathways like Wnt, Hedgehog (Hh), and Notch is attributed towards the rise of CSCs. Recent breakthroughs offer better insights into CSC signaling. Scientists have developed several combinatorial therapies like targeting one/multiple of these CSC pathways. The article summarized various markers used to identify CSCs and discuss major signaling pathways in them. The futuristic probabilities to use CSC therapeutics in clinical development have been discussed. Our views have been highlighted on the future directions for targeting advances in the clinical development. ? 2018, Springer Science+Business Media, LLC, part of Springer Nature.