School Of Basic And Applied Sciences
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Item The incidence of male breast cancer: from fiction to reality - correspondence(NLM (Medline), 2023-05-24T00:00:00) Mukherjee, Anirban Goutam; Gopalakrishnan, Abilash Valsala; Jayaraj, Rama; Renu, Kaviyarasi; Dey, Abhijit; Vellingiri, Balachandar; Malik, Tabarak[No abstract available]Item The creation of selenium nanoparticles decorated with troxerutin and their ability to adapt to the tumour microenvironment have therapeutic implications for triple-negative breast cancer(Royal Society of Chemistry, 2023-02-09T00:00:00) Saranya, Thiruvenkataswamy; Kavithaa, Krishnamoorthy; Paulpandi, Manickam; Ramya, Sennimalai; Winster, Sureshbabu Harysh; Mani, Geetha; Dhayalan, Sangeetha; Balachandar, Vellingiri; Narayanasamy, ArulDespite advancements in treatment, managing aggressive types of breast cancer, particularly Triple Negative Breast Cancer (TNBC), remains a daunting task. Newer chemotherapeutics enhance the multidrug resistance in cancer cells, making them untreatable. The current research work was framed to develop a novel therapeutic target by utilizing the flavanol, troxerutin (TXN) as a drug of interest to target TNBC. And also, to increase the efficiency of the drug at the target site, a nanocarrier called selenium nanoparticles (SeNPs) has been exploited. Thus, the anticancer efficacy of TXN and Se-TXN against TNBC (in vitro and in vivo) has been compared and analysed in the present study. Se-TXN was synthesized by a precipitation approach and characterized by diverse analytical techniques, which confirmed the successful loading of TXN on the SeNPs. The inhibitory concentration (IC50) of Se-TXN was determined to be 6.5 � 0.5 ?g mL?1 according to the in vitro data. Even at lower concentrations, the existence of apoptotic bodies shows that Se-TXN is effective against TNBC. Additionally, the Se-TXN expression study shows that the activation of the caspase cascade pathway, which results in apoptosis, occurs from the downregulation of anti-apoptotic proteins and genes and the upregulation of pro-apoptotic proteins and genes. And the in vivo investigations like histopathology, hematology and biochemical parameters revealed that the Se-TXN had significantly lowered the tumour volume of treated Balb/C mice without having any significant systemic toxicity when compared to other treatment groups. Altogether, our data suggests the efficacy of Se-TXN nanoconjugates as an effective management therapy for treating TNBC. � 2023 The Royal Society of Chemistry.Item Evolution of Frozen Section in Carcinoma Breast: Systematic Review(Hindawi Limited, 2022-05-23T00:00:00) Rana, Manjit Kaur; Rana, Amrit Pal Singh; Sharma, Uttam; Barwal, Tushar Singh; Jain, AklankBackground. The frozen section (FS) has been a good technique in surgical management of breast lesions since many years. But complete agreement and cooperation have not been achieved everywhere among surgeons and pathologists especially in the developing countries. FS undergoes continuous criticism due to various shortcomings but continued to be evaluated especially in developing countries. Objectives. This review was conducted to synthesize information on the use of frozen section in carcinoma breast. Data Sources. The MEDLINE database for frozen section since its origin and its implication in recent breast surgery techniques was studied. Study Eligibility Criteria. Sixty-five articles were reviewed with complete analysis on FS in both benign and malignant breast lesions. Study Appraisal and Synthesis Methods. The analysis of frozen section was done as a diagnostic tool in breast lesions, margin status in breast conservative surgery in carcinoma breast, and sentinel lymph node and use of immunohistochemistry for sentinel lymph node FS. Results. It was analysed that the FS gives accurate results in margin status analysis, decreasing rerecurrence. Conclusion. The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis are the key points of its use in breast conservative surgery. Its use in sentinel lymph node biopsy (SLNB) is equivocal. However, application of immunohistochemistry on frozen section of SLNB is an evolving trend in today's era. � 2022 Manjit Kaur Rana et al.Item Quantification and optimization of clot retraction in washed human platelets by Sonoclot coagulation analysis(John Wiley and Sons Inc, 2021-10-07T00:00:00) Yadav, Pooja; Beura, Samir K.; Panigrahi, Abhishek R.; Singh, Sunil K.Introduction: Clot retraction is a pivotal process for haemostasis, where platelets develop a contractile force in fibrin meshwork and lead to the increased rigidity of clot. The pathophysiological alteration in contractile forces generated by the platelet-fibrin meshwork can lead to haemostatic disorders. Regardless of its utter significance, clot retraction remains a limited understood process owing to lack of quantification methodology. Sonoclot analysis is a point-of-care technique used in clinical laboratories for whole blood analysis that provides�in vitro�qualitative as well as quantitative assessment of coagulation process from initial fibrin formation to clot retraction. Methods: Human washed platelets were isolated by differential centrifugation method and analysed via optical imaging, microscopy and Sonoclot analysis using 1-2�נ108/mL of washed platelets, 1�U/mL of thrombin, 1�mg/mL of fibrinogen and 1�mM of calcium chloride. Results: In this study, we demonstrate the novelty of this instrument in the quantitative evaluation of clot retraction in washed platelets and attempted to optimize the reference range of Sonoclot parameters including ACT - 87.3���20.997, CR - 16.23���3.538 and PF - 3.57���0.629, (n�=�10). Discussion: Sonoclot analysis provides a simple and quantitative method to better understand in vitro clot retraction and its modulation by retraction components including platelet count, fibrinogen and platelet�fibrin interaction compared with existing conventional methods. Sonoclot may prove to be a valuable tool in thrombus biology research to understand fundamental basis of blood clot retraction. � 2021 John Wiley & Sons LtdItem Dopamine, sleep, and neuronal excitability modulate amyloid-?-mediated forgetting in Drosophila(Public Library of Science, 2021-10-07T00:00:00) Kaldun, Jenifer C.; Lone, Shahnaz R.; Humbert Camps, Ana M.; Fritsch, Cornelia; Widmer, Yves F.; Stein, Jens V.; Tomchik, Seth M.; Sprecher, Simon G.Alzheimer disease (AD) is one of the main causes of age -related dementia and neurodegeneration. However, the onset of the disease and the mechanisms causing cognitive defects are not well understood. Aggregation of amyloidogenic peptides is a pathological hallmark of AD and is assumed to be a central component of the molecular disease pathways. Panneuronal expression of A?42 Arctic peptides in Drosophila melanogaster results in learning and memory defects. Surprisingly, targeted expression to the mushroom bodies, a center for olfactory memories in the fly brain, does not interfere with learning but accelerates forgetting. We show here that reducing neuronal excitability either by feeding Levetiracetam or silencing of neurons in the involved circuitry ameliorates the phenotype. Furthermore, inhibition of the Rac-regulated forgetting pathway could rescue the A?42 Arctic-mediated accelerated forgetting phenotype. Similar effects are achieved by increasing sleep, a critical regulator of neuronal homeostasis. Our results provide a functional framework connecting forgetting signaling and sleep, which are critical for regulating neuronal excitability and homeostasis and are therefore a promising mechanism to modulate forgetting caused by toxic A? peptides. � 2021 Kaldun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Item Biosynthesis of Zinc Oxide Nanoparticles Using Catharanthus Roseus Leaves and Their Therapeutic Response in Breast Cancer (MDA-MB-231) Cells(Routledge, 2021-07-26T00:00:00) Bangroo, Apoorva; Malhotra, Akshay; Sharma, Uttam; Jain, Aklank; Kaur, AnupreetAs the current study reports the utilization of the leaf extract of Catharanthus roseus (C.roseus) for the biological synthesis of zinc oxide nanoparticles (ZnO NPs) because of the importance of the importance of health and environment. Bioinspired synthesis were characterized using Fourier Transform Infrared Spectroscopy (FT-IR), Field Emission-Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy-Dispersive X-ray Spectroscopy (EDX) and X-Ray diffraction (XRD). XRD and TEM micrograph analysis revealed that the synthesized nanostructures were well-dispersed and spherical with the average particle size in the 18-30 nm range were produced. The FT-IR spectra confirmed presence of phenolic compounds that act as reducing and capping agents. Further, it suggested the possible utilization of hydroxyl groups and amides in the reduction of Zn ions and stablization of ZnO NPs. Zinc oxide nanomaterials are effective in cancer treatments, including the destruction of tumor cells with minimal damage to healthy cells. The toxicity of zinc oxide nanomaterials was checked in vitro in the human breast cancer line MDA-MB-231. Inverse relation of the percentage of viable cells to the concentration of zinc oxide nanomaterials at increasing molar levels was assessed. The cytotoxicity analysis used in the MTT test shows the substantial viable MDA-MB-231-cells despite the increased concentration of exposure to zinc oxide nanomaterials. Reduction in the ratio of viable MDA-MB-231 cells after being exposed to zinc oxide nanomaterials was compared to untreated cancerous cells. The present approach to biosynthesis is quick, inexpensive, eco-friendly, and high-rise stable nanomaterials of zinc oxide with substantial cancer potential. This is the first study that reports molar concentrations (with the lowest concentration of 10 mM) as an anticancer agent for breast cancer and potential clinical uses for synthesized zinc oxide nanomaterials. Thus, C. roseus based synthesized ZnO NPs could be explored not only as environmentally benign method but also as a potential anti-carcinogenic agent. � 2022 Taylor & Francis Group, LLC.Item MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives(Royal Society of Chemistry, 2023-08-10T00:00:00) Ram, Teja; Singh, Ankit Kumar; Kumar, Adarsh; Singh, Harshwardhan; Pathak, Prateek; Grishina, Maria; Khalilullah, Habibullah; Jaremko, Mariusz; Emwas, Abdul-Hamid; Verma, Amita; Kumar, PradeepMEK1/2 are critical components of the RAS-RAF-MEK-ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to have a MEK mutation (encoding MEK2P298L). MEK is involved in various human cancers such as non-small cell lung cancer (NSCLC), spurious melanoma, and pancreatic, colorectal, basal, breast, and liver cancer. To date, 4 MEK inhibitors i.e., trametinib, cobimetinib, selumetinib, and binimetinib have been approved by the FDA and several are under clinical trials. In this review, we have highlighted structural insights into the MEK1/2 proteins, such as the ?C-helix, catalytic loop, P-loop, F-helix, hydrophobic pocket, and DFG motif. We have also discussed current issues with all FDA-approved MEK inhibitors or drugs under clinical trials and combination therapies to improve the efficacy of clinical drugs. Finally, this study addressed recent developments on synthetic MEK inhibitors (from their discovery in 1997 to 2022), their unique properties, and their relevance to MEK mutant inhibition. � The Royal Society of Chemistry 2023.Item PROTAC�ing oncoproteins: targeted protein degradation for cancer therapy(BioMed Central Ltd, 2023-03-30T00:00:00) Kelm, Jeremy M.; Pandey, Deepti S.; Malin, Evan; Kansou, Hussein; Arora, Sahil; Kumar, Raj; Gavande, Navnath S.Molecularly targeted cancer therapies substantially improve patient outcomes, although the durability of their effectiveness can be limited. Resistance to these therapies is often related to adaptive changes in the target oncoprotein which reduce binding affinity. The arsenal of targeted cancer therapies, moreover, lacks coverage of several notorious oncoproteins with challenging features for inhibitor development. Degraders are a relatively new therapeutic modality which deplete the target protein by hijacking the cellular protein destruction machinery. Degraders offer several advantages for cancer therapy including resiliency to acquired mutations in the target protein, enhanced selectivity, lower dosing requirements, and the potential to abrogate oncogenic transcription factors and scaffolding proteins. Herein, we review the development of proteolysis targeting chimeras (PROTACs) for selected cancer therapy targets and their reported biological activities. The medicinal chemistry of PROTAC design has been a challenging area of active research, but the recent advances in the field will usher in an era of rational degrader design. � 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.Item Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities(American Chemical Society, 2023-02-22T00:00:00) Maity, Pritam; Chatterjee, Joydeep; Patil, Kiran T.; Arora, Sahil; Katiyar, Madhurendra K.; Kumar, Manvendra; Samarbakhsh, Amirreza; Joshi, Gaurav; Bhutani, Priyadeep; Chugh, Manoj; Gavande, Navnath S.; Kumar, RajEpidermal growth factor receptor (EGFR) is an oncogenic drug target and plays a critical role in several cellular functions including cancer cell growth, survival, proliferation, differentiation, and motility. Several small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) have been approved for targeting intracellular and extracellular domains of EGFR, respectively. However, cancer heterogeneity, mutations in the catalytic domain of EGFR, and persistent drug resistance limited their use. Different novel modalities are gaining a position in the limelight of anti-EGFR therapeutics to overcome such limitations. The current perspective reflects upon newer modalities, importantly the molecular degraders such as PROTACs, LYTACs, AUTECs, and ATTECs, etc., beginning with a snapshot of traditional and existing anti-EGFR therapies including small molecule inhibitors, mAbs, and antibody drug conjugates (ADCs). Further, a special emphasis has been made on the design, synthesis, successful applications, state-of-the-art, and emerging future opportunities of each discussed modality. � 2023 American Chemical Society.Item A Perspective on Medicinal Chemistry Approaches for Targeting Pyruvate Kinase M2(American Chemical Society, 2021-11-02T00:00:00) Arora, Sahil; Joshi, Gaurav; Chaturvedi, Anuhar; Heuser, Michael; Patil, Santoshkumar; Kumar, RajThe allosteric regulation of pyruvate kinase M2 (PKM2) affects the switching of the PKM2 protein between the high-activity and low-activity states that allow ATP and lactate production, respectively. PKM2, in its low catalytic state (dimeric form), is chiefly active in metabolically energetic cells, including cancer cells. More recently, PKM2 has emerged as an attractive target due to its role in metabolic dysfunction and other interrelated conditions. PKM2 (dimer) activity can be inhibited by modulating PKM2 dimer�tetramer dynamics using either PKM2 inhibitors that bind at the ATP binding active site of PKM2 (dimer) or PKM2 activators that bind at the allosteric site of PKM2, thus activating PKM2 from the dimer formation to the tetrameric formation. The present perspective focuses on medicinal chemistry approaches to design and discover PKM2 inhibitors and activators and further provides a scope for the future design of compounds targeting PKM2 with better efficacy and selectivity. � 2021 American Chemical Society