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Dual treatments targeting IGF-1R, PI3K, mTORC or MEK synergize to inhibit cell growth, induce apoptosis, and arrest cell cycle at G1 phase in MDA-MB-231 cell line

Ayub A, Yip WK, Seow HF

Biomed Pharmacother, 2015 Oct;75:40-50.
PMID: 26463630 DOI: 10.1016/j.biopha.2015.08.031

Triple-negative breast cancers (TNBCs) are aggressive cancers that do not benefit from hormonal therapy or therapies that target HER2 receptors. Insulin-like growth factor 1 receptor (IGF-1R), which has been shown to be overexpressed in breast cancer, activates numerous downstream kinases that associate with cell proliferation and survival. This study compared the effects caused by dual treatments targeting IGF-1R, PI3K, mTORC, or MEK with those by single treatments in a TNBC cell line, MDA-MB-231. We used small-molecule kinase inhibitors, namely, NVP-AEW541, NVP-BKM120, KU0063794, and PD0325901 to target IGF-1R, PI3K, mTORC, and MEK, respectively. Combination treatments of PD0325901 with NVP-AEW541, NVP-BKM120 or KU0063794 and NVP-AEW541 with KU0063794 demonstrated a significant synergistic growth inhibition. These dual treatments increased apoptosis and/or cell cycle arrest at G0/G1 phase and enhanced the inhibition of phosphorylation of Akt or downstream molecules of mTORC1, as compared to the single treatments. Our study suggests that targeting multiple kinases in IGF-1R signaling may be a promising therapeutic approach.
Effects of prolonged running in the heat and cool environments on selected physiological parameters and salivary lysozyme responses

Ibrahim NS, Chen CK, Ayub A, Muhamad AS

J Exerc Sci Fit, 2017 Dec;15(2):63-69.
PMID: 29541134 DOI: 10.1016/j.jesf.2017.08.002

Introduction: Lysozyme is one of the salivary antimicrobial proteins which act as the "first line of defence" at the mucosal surface. The effects of prolonged exercise in the hot and cool environments among recreational athletes on salivary lysozyme responses are very limited in the literature, especially in the Asian countries.
Objective: To determine the effects of prolonged running in the hot and cool environments on selected physiological parameters and salivary lysozyme responses among recreational athletes.
Methods: Randomised and cross-over study design. Thirteen male recreational athletes (age: 20.9 ± 1.3 years old) from Universiti Sains Malaysia participated in this study. They performed two separate running trials; 90 min running at 60% of their respective maximum oxygen uptake [Formula: see text] One running trial was performed in the hot (31ºC) while the other was in the cool (18ºC) environment and this sequence was randomised. Each running trial was started with a 5 min warm-up at 50% of participant's respective [Formula: see text] Recovery period between these two trials was one week. In the both trials, saliva samples, blood samples, heart rate, ratings of perceived exertion, skin and tympanic temperatures, oxygen consumption, nude body weight, room temperature, and relative humidity were collected.
Results: Participants' skin temperature, tympanic temperature, body weight changes, heart rate, ratings of perceived exertion, and plasma volume changes were significantly higher (p
High-dose pulse methylprednisolone vs. dexamethasone standard therapy for severe and critical COVID-19 pneumonia: Efficacy assessment in a retrospective single-centre experience from Malaysia

Soo CI, Poon KV, Ayub A, You HW, Tan CX, Loh KJJ, et al.

Med J Malaysia, 2024 Jan;79(1):15-20.
PMID: 38287752

INTRODUCTION: The use of dexamethasone (DXM) has been associated with decreased mortality in the patients with hypoxemia during the coronavirus disease-2019 (COVID-19) pandemic, while the outcomes with methylprednisolone (MTP) have been mixed. This real-life study aimed to evaluate the outcomes of patients with severe respiratory failure due to COVID-19 who were treated with high doses of MTP.
MATERIALS AND METHODS: This retrospective cohort study enrolled hospitalised patients between May 2021 and August 2021, aged 18 years and above, with severe respiratory failure defined by a ratio of oxygen saturation to fraction of inspired oxygen (SF ratio) of less than 235. The treatment protocol involved administering high-dose MTP for 3 days, followed by DXM, and the outcomes were compared with those of patients who received DXM alone (total treatment duration of 10 days for both groups).
RESULTS: A total of 99 patients were enrolled, with 79 (79.8%) receiving pulse MTP therapy and 20 (20.2%) being treated with DXM only. The SF ratio significantly improved from a mean of 144.49 (±45.16) at baseline to 208 (±85.19) at 72 hours (p < 0.05), with a mean difference of 63.51 (p < 0.001) in patients who received ≤750 mg of MTP. Additionally, in patients who received >750 mg of MTP, the SF ratio improved from a baseline mean of 130.39 (±34.53) to 208.44 (±86.61) at 72 hours (p < 0.05), with a mean difference of 78.05 (p = 0.001). In contrast, patients who received DXM only demonstrated an SF ratio of 132.85 (±44.1) at baseline, which changed minimally to 133.35 (±44.4) at 72 hours (p = 0.33), with a mean difference of 0.50 (p = 0.972). The incidence of nosocomial infection was higher in the MTP group compared with the DXM group (40.5% vs. 35%, p = 0.653), with a relative risk of 1.16 (95% CI: 0.60-2.23).
CONCLUSION: MTP did not demonstrate a significant reduction in intubation or intensive care unit admissions. Although a high dose of MTP improved gas exchange in patients with severe and critical COVID-19, it did not provide an overall mortality benefit compared to standard treatment.

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