Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item In silico identification and in vitro validation of alpha-hederin as a potent inhibitor of Wnt/β-catenin signaling pathway in breast cancer stem cells.(Springer-Verlag, GmbH, 2024) Saliu, T.P.; Seneviratne, N.N.; Faizan, M.; Rajagopalan, U.; Perera, D.C.; Adhikari, A.; Senathilake, K.S.; Galhena, P.B.; Tennekoon, K.H.; Samarakoon, S.R.Cancer stem cells (CSCs) play a vital role in metastasis, recurrence and chemoresistance in breast cancer. β-catenin, which is a frequently over activated protein in CSCs, binds to T-cell factor/lymphoid enhancer factor (Tcf/Lef) family transcription factors leading to ectopic expression of Wnt pathway responsive genes necessary for the maintenance and action of CSCs. With the aim of identifying a small molecules that can effectively eliminate CSCs, molecular docking studies were performed against the Tcf/Lef binding hotspot on β-catenin using a library of 100 natural or synthetic small molecules. Small molecule ligands giving docking energy better than - 7 kcal/mol were further investigated by binding interactions analysis and molecular dynamics (MD) simulations. These compounds were then investigated in vitro, for cytotoxicity against CSCs isolated from MDA-MB-231 triple negative breast cancer cells. Alpha-hederin (AH) was identified as the only compound in the selected library that has cytotoxicity against breast CSCs. AH was further investigated for it's ability to regulate Wnt pathway target genes (Cyclin D1 and CD44)and the tumor suppressor p53by real-time quantitative PCR. Absorption, distribution, metabolism, excretion and toxicity properties of the AH was predicted in silico. AH significantly down regulated the transcription of Cyclin D1 and CD44 while up-regulating the transcription of p53. AH was predicted to have acceptable drug likeness. Although AH is currently known to inhibit the growth of various cancer cells in vitro, present study demonstrated for the first time that it is a potent inhibitor of Wnt/β-catenin signaling pathway and induce apoptosis in breast CSCs.Item The relationship between delaying physiotherapy intervention commencement and lymphedema among breast cancer survivors in Sri Lanka(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2021) Weerarathne, B.O.K.; Samudika, V.G.G.; Arunakanthi, A.M.; Dabare, H.P.M.; Malaviarachchi, S.L.Introduction: The recent cancer statistics in Sri Lanka evaluated breast cancer as the most common cancer among female population with cancers. Due to the better survival rate, Modified Radical Mastectomy surgery is an ideal surgical management for most of the breast cancer stages. Upper limb lymphedema is a known post-surgical complication which has long-life impact on breast cancer survivors that can be easily managed with early physiotherapy intervention. Objective: This study was aimed to identify the relationship between delaying physiotherapy intervention and lymphedema volume among breast cancer survivors at Apeksha hospital, Maharagama, Sri Lanka. Methods: 74 female breast cancer patients newly referred to the department of physiotherapy were recruited for this study. Patients undergone bilateral surgeries were excluded from the study. An interviewer-administered questionnaire was used to collect information of socio-demographic data and underwent surgical procedures. The severity of upper limb lymphedema was assessed by measuring the lymphedema volume according to the frustum model formula, using multiple circumferential measurements. International Society of Lymphology staging system was used to identify the distribution of lymphedema severity. Results: Within the sample, delayed period to commence physiotherapy after the surgery ranged from < 1 to 17 years. The lymphedema severity stages minimal, moderate and severe among the sample recorded as 37.8%, 50.0% and 12.2% respectively. A significant positive correlation was observed between delayed period to start physiotherapy and lymphedema volume (p=0.05, r= 0.75). Conclusions: The lymphedema volume increases with time of delayed physiotherapy intervention. Hence, the patients are required to participate in early physiotherapy intervention.