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

A deep radius valley revealed by Kepler short cadence observations

The characteristics of the radius valley, i.e. an observed lack of planets between 1.5 and 2 Earth radii at periods shorter than about 100 d, provide insights into the formation and evolution of close-in planets. We present a novel view of the radius valley by refitting the transits of 431 planets using Kepler 1-min short cadence observations, the vast majority of which have not been previously analysed in this way. In some cases, the updated planetary parameters differ significantly from previous studies, resulting in a deeper radius valley than previously observed. This suggests that planets are likely to have a more homogeneous core composition at formation. Furthermore, using support vector machines, we find that the radius valley location strongly depends on orbital period and stellar mass and weakly depends on stellar age, with ∂ log Rp,valley /∂ log P = −0.096+0.023 −0.027, ∂ log Rp,valley /∂ log M = 0.231+0.053 −0.064, and ∂ log Rp,valley /∂ log (age) = 0.033+0.017 −0.025. These findings favour thermally driven mass-loss models such as photoevaporation and core-powered mass-loss, with a slight preference for the latter scenario. Finally, this work highlights the value of transit observations with a short photometric cadence to precisely determine planet radii, and we provide an updated list of precisely and homogeneously determined parameters for the planets in our sample

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

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

Understanding and predicting cadence effects in the characterization of exoplanet transits

We investigate the effect of observing cadence on the precision of radius ratio values obtained from transit light curves by performing uniform Markov chain Monte Carlo fits of 46 exoplanets observed by the Transiting Exoplanet Survey Satellite (TESS) in multiple cadences. We find median improvements of almost 50 per cent when comparing fits to 20 and 120 s cadence light curves to 1800 s cadence light curves, and of 37 per cent when comparing 600 s cadence to 1800 s cadence. Such improvements in radius precision are important, for example, to precisely constrain the properties of the radius valley or to characterize exoplanet atmospheres. We also implement a numerical information analysis to predict the precision of parameter estimates for different observing cadences. We tested this analysis on our sample and found that it reliably predicts the effect of shortening observing cadence with errors in the predicted percentage precision of $\lesssim0.5~{{\ \rm per\ cent}}$ for most cases. We apply this method to 157 TESS objects of interest that have only been observed with 1800 s cadence to predict the precision improvement that could be obtained by reobservations with shorter cadences and provide the full table of expected improvements. We report the 10 planet candidates that would benefit the most from reobservations at short cadence. Our implementation of the information analysis for the prediction of the precision of exoplanet parameters, Prediction of Exoplanet Precisions using Information in Transit Analysis, is made publicly available

The prevalence of Helicobacter pylori carrier rates among the healthy blood donors in Hong Kong

A serological assay was employed in this study to assess the Helicobacter pylori carrier rates among the healthy blood donors (all Chinese) in Hong Kong. The commercial kit for detecting anti-H. pylori antibody titres was found to have a sensitivity of 84% and a specificity of 85% by using the histochemistry results as the gold standard. Elevated anti-H. pylori antibody titres were observed in 42.4%, 53.2% and 72.2% of the healthy blood donors of age below 20, 21 to 30 and 31 to 40 years respectively. This indicates a steady rise of H. pylori carrier rates with age. The overall H. pylori prevalence rate was 54.9%. The positivity of H. pylori in teenagers appeared to be double that reported in Western countries. Whether this is related to the younger age of peptic ulcer presentation in Hong Kong compared with Western countries is not known. However, there was no significant difference of the H. pylori rates between males and females of each age group although a male predominance has been well established for peptic ulcer in Hong Kong.published_or_final_versio

The effect of SARS on the price of re-entrants in multi-storey apartment buildings

Natural lighting and ventilation have long been a primary consideration in building design, particularly for those high-rise and densely packed apartment blocks where mechanical ventilation is normally secondary. In Hong Kong, there are prescriptive legal requirements governing the provision of natural lighting and ventilation in private buildings. This, coupled with developers’ profit-maximizing incentives, often gives rise to re-entrant designs commonly found in apartment buildings in Hong Kong. This paper aims to study the economic impacts of the disposition of re-entrants on property prices with reference to the revelation of the chimney effect of re-entrants after the occurrence of the mass community outbreak of Severe Acute Respiratory Disease (SARS) in Amoy Gardens in 2003. In this study, we use a hedonic pricing model to examine whether flats designed with a re-entrant is sold at a different price than those without a re-entrant. We draw a sample of property transactions from a popular single residential development with variations in re-entrant designs. A total of 357 transactions were collected, of which 90 were transacted after the SARS event. The model is capable to monitor any significance changes in the premium of re-entrant and its relationship with floor level before and after SARS. Based on the hedonic pricing analysis, we found that the preference for re-entrants is floor-dependent. Before SARS, homebuyers were not fond of re-entrants on low floor levels, but they were willing to pay more for re-entrants as the floor level increases. Yet, the outbreak of SARS did not significantly change their preferences for re-entrants. The market is capable to capitalize the building design into property prices. Developers and designs should improve their building design to meet the ever changing needs of the market. This paper provides an empirical framework to examine how homebuyers price a particular design feature using property transaction data.published_or_final_versio