@article {6687, title = {Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.}, journal = {J Invest Dermatol}, volume = {143}, year = {2023}, month = {2023 May}, pages = {699-710.e10}, abstract = {

Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor SNAI1 is overexpressed in the epidermis of patients with systemic sclerosis, and a transgenic mouse recapitulating this expression pattern is sufficient to induce many clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin (SPON2) in fibrogenesis. Mindin is produced by SNAI1 transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.

}, keywords = {Animals, Disease Models, Animal, Extracellular Matrix Proteins, Fibroblasts, Fibrosis, Humans, Mice, Mice, Transgenic, Neoplasm Proteins, Scleroderma, Systemic, Skin}, issn = {1523-1747}, doi = {10.1016/j.jid.2022.10.011}, author = {Rana, Isha and Kataria, Sunny and Tan, Tuan Lin and Hajam, Edries Yousaf and Kashyap, Deepak Kumar and Saha, Dyuti and Ajnabi, Johan and Paul, Sayan and Jayappa, Shashank and Ananthan, Akhil S H P and Kumar, Pankaj and Zaarour, Rania F and Haarshaadri, J and Kansagara, Gaurav and Rizvi, Abrar and Zirmire, Ravindra K and Badarinath, Krithika and Khedkar, Sneha Uday and Chandra, Yogesh and Samuel, Rekha and George, Renu and Danda, Debashish and Jacob, Paul Mazhuvanchary and Dey, Rakesh and Dhandapany, Perundurai S and He, You-Wen and Varga, John and Varghese, Shyni and Jamora, Colin} } @article {6890, title = {Advances in targeting the WNT/β-catenin signaling pathway in cancer.}, journal = {Drug Discov Today}, volume = {27}, year = {2022}, month = {2022 Jan}, pages = {82-101}, abstract = {

WNT/β-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/β-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/β-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/β-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/β-catenin inhibitors to the clinic for cancer therapy.

}, keywords = {Biological Products, Drug Design, Humans, Molecular Targeted Therapy, Neoplasms, Wnt Signaling Pathway}, issn = {1878-5832}, doi = {10.1016/j.drudis.2021.07.007}, author = {Chatterjee, Avradip and Paul, Sayan and Bisht, Bharti and Bhattacharya, Shelley and Sivasubramaniam, Sudhakar and Paul, Manash K} } @article {6899, title = {Drug repurposing-an emerging strategy in cancer therapeutics.}, journal = {Naunyn Schmiedebergs Arch Pharmacol}, volume = {395}, year = {2022}, month = {2022 Oct}, pages = {1139-1158}, abstract = {

Cancer is a complex disease affecting millions of people around the world. Despite advances in surgical and radiation therapy, chemotherapy continues to be an important therapeutic option for the treatment of cancer. The current treatment is expensive and has several side effects. Also, over time, cancer cells develop resistance to chemotherapy, due to which there is a demand for new drugs. Drug repurposing is a novel approach that focuses on finding new applications for the old clinically approved drugs. Current advances in the high-dimensional multiomics landscape, especially proteomics, genomics, and computational omics-data analysis, have facilitated drug repurposing. The drug repurposing approach provides cheaper, effective, and safe drugs with fewer side effects and fastens the process of drug development. The review further delineates each repurposed drug{\textquoteright}s original indication and mechanism of action in cancer. Along with this, the article also provides insight upon artificial intelligence and its application in drug repurposing. Clinical trials are vital for determining medication safety and effectiveness, and hence the clinical studies for each repurposed medicine in cancer, including their stages, status, and National Clinical Trial (NCT) identification, are reported in this review article. Various emerging evidences imply that repurposing drugs is critical for the faster and more affordable discovery of anti-cancerous drugs, and the advent of artificial intelligence-based computational tools can accelerate the translational cancer-targeting pipeline.

}, keywords = {Antineoplastic Agents, Artificial Intelligence, Drug Repositioning, Humans, Neoplasms}, issn = {1432-1912}, doi = {10.1007/s00210-022-02263-x}, author = {Turabi, Khadija Shahab and Deshmukh, Ankita and Paul, Sayan and Swami, Dayanand and Siddiqui, Shafina and Kumar, Urwashi and Naikar, Shreelekha and Devarajan, Shine and Basu, Soumya and Paul, Manash K and Aich, Jyotirmoi} } @article {6861, title = {Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.}, journal = {Biomolecules}, volume = {11}, year = {2021}, month = {2021 Aug 25}, abstract = {

Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management.

}, keywords = {Animals, Apoptosis, Cardiac Glycosides, Clinical Trials as Topic, Humans, Molecular Docking Simulation, Neoplasms, Transcription Factors}, issn = {2218-273X}, doi = {10.3390/biom11091275}, author = {Kumavath, Ranjith and Paul, Sayan and Pavithran, Honey and Paul, Manash K and Ghosh, Preetam and Barh, Debmalya and Azevedo, Vasco} }