Combination of Arginine Depletion and Chemotherapy in Thoracic Malignancies

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Arsenic trioxide suppresses tumour growth in squamous cell lung carcinoma

This journal suppl. entitled: 20th Medical Research Conference; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong KongINTRODUCTION: Squamous cell lung carcinoma (SCC) belongs to the second most common subtype in non–small-cell lung carcinoma. Recently, doublet chemotherapy regimens remain the cornerstone of first-line systemic treatment. Therefore, new therapeutic approach is urgently needed. Arsenic trioxide (ATO) is a traditional Chinese medicine which has multiple anti-cancer mechanisms including apoptosis. ATO has been used clinically in acute promyelocytic leukaemia. ATO has been shown to induce apoptosis in lung adenocarcinoma …published_or_final_versio

Inhibition of ornithine decarboxylase facilitates pegylated arginase treatment in lung adenocarcinoma xenograft models

INTRODUCTION: Arginine depletion has shown anticancer effects among arginine auxotrophic cancers. Pegylated arginase (BCT-100) depletes arginine by converting arginine to ornithine. In this study, BCT-100 inhibited cell growth in a panel of lung adenocarcinoma cell lines while stimulated tumor growth in most lung adenocarcinoma xenograft models. Furthermore, ornithine decarboxylase (ODC) was induced by BCT-100 in two solid xenograft models with tumor growth stimulating effect. We postulate that accumulated ornithine was used to produce polyamines by ODC which promoted tumor growth. And ODC inhibition might rescue the therapeutic effect of BCT-100 treatment in lung adenocarcinoma ...published_or_final_versio

Massive degradation in FGFR/Akt/Erk signaling by arsenic trioxide and FGFR inhibitor PD173074 in squamous cell lung carcinoma SK-MES-1

This journal suppl. entitled: 20th Medical Research Conference; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong KongINTRODUCTION: Lung cancer is the top cancer killer. Squamous cell carcinoma (SCC) represents the second most common histological subtype of lung cancer. Arsenic trioxide (ATO) has been demonstrated to inhibit tumour growth in lung adenocarcinoma and initiate apoptosis in acute promyelocytic leukaemia. Fibroblast growth factor (FGF) receptor (FGFR) amplification is shown in some SCC. FGFR inhibitor (eg PD173074) has been …published_or_final_versio

Gastro-oesophageal reflux in bronchiectasis

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Arsenic trioxide-induced cytotoxicity in small cell lung cancer via altered redox homeostasis and mitochondrial integrity.

Arsenic trioxide (ATO) has demonstrated anticancer activity in different malignancies, especially acute promyelocytic leukemia, with a wide array of putative mechanisms. In this study, we aimed to elucidate the activity and mechanisms of ATO in small cell lung cancer (SCLC). A panel of SCLC cell lines (H841, DMS79, H526, H69 and H187) was employed to demonstrate the activity of ATO. Cell viability, apoptosis and mitochondrial membrane depolarization were assessed. Western blotting was performed to determine the alteration of pro-apoptotic and anti-apoptotic mediators. Reactive oxygen species (ROS) (hydrogen peroxide and superoxide) and intracellular glutathione (GSH) were measured. Antioxidants, N-acetyl-L-cysteine (NAC) and butylated hydroxyanisole (BHA), were applied to restore GSH content and reduce production of ROS. All SCLC cell lines were relatively sensitive to ATO with IC50 values below 10 µM. ATO induced cell death mainly through apoptosis in H841 cells in a dose-dependent manner. Hydrogen peroxide was the major ROS in SCLC cells induced by ATO. Along with GSH depletion and Bcl-2 downregulation, mitochondrial membrane permeabilization was enhanced, followed by release of AIF and SMAC from mitochondria to initiate different cell death pathways. NAC reversed cell death and molecular changes induced by ATO via restoring GSH and reducing ROS content. BHA inhibited hydrogen peroxide production completely and partially restored GSH content accounting for partial reversal of cell inhibition and mitochondrial dysfunction. Nonetheless, ATO reduced both reduced and oxidized form of thioredoxin 1 (Trx1) with no effect on Trx1 redox potential. ATO led to cell death in SCLC mainly through mitochondrial dysfunction, resulting from altered cellular redox homeostasis, namely, hydrogen peroxide generation, GSH depletion and Trx1 downregulation.published_or_final_versio

Exhaled nitric oxide predicts lung function but not quality of life in subjects with non-small cell lung cancer

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The Effect of Tumor Microenvironment on Autophagy and Sensitivity to Targeted Therapy in EGFR-Mutated Lung Adenocarcinoma

Lung cancer is the top cancer killer worldwide. Tyrosine kinase inhibitors (TKIs), for example erlotinib, are commonly used to target epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (ADC). Autophagy is a cellular response to stress, serving as a protective mechanism during anticancer therapy. The tumor microenvironment (TME) is composed of non-tumor cells that include fibroblasts. Our study aimed to investigate the effect of TME on autophagy and TKI sensitivity. Following cell sorting after direct co-culturing, autophagy and cytokine production were observed in both HCC827 and MRC-5 cells. The synergistic combination of erlotinib and chloroquine (autophagy inhibitor) was observed under TME. Tumor growth was significantly suppressed with combined erlotinib/chloroquine compared with erlotinib in HCC827 xenografts.published_or_final_versio

Lymphangioleimyomatosis: a Hong Kong cohort

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A pilot study of the serum telomerase activity in non-small cell lung cancer (NSCLC)

Session - Respiratory & Critical Care Medicine: no. S-RC-3published_or_final_versio