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Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer cases. Small cell lung cancer is characterized by frequent relapse, and current treatments lack tumor specificity. Arginine is a non‐essential amino acid for human normal cells but critical to some tumor cells that cannot synthesize arginine. Therefore, arginine deprivation has become a potential therapeutic option for selected tumors. BCT‐100 is a pegylated arginase that has documented anticancer activity in arginine auxotrophic tumors, such as melanoma, hepatocellular carcinoma, and acute myeloid leukemia. One of the resistance mechanisms to arginase treatment is overexpression of argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC), two important enzymes in the urea cycle. We selected 9 SCLC and 1 non‐small cell lung carcinoma cell lines to determine the growth inhibition effects of BCT‐100 and established that cell lines with low expression of ASS1 and OTC are relatively sensitive to BCT‐100 treatment. Knocking down OTC in a H841 cell line could potentiate its sensitivity to BCT‐100 treatment. Arginine concentration was sharply decreased, accompanied by apoptosis through oxidative stress as well as G1 cell cycle arrest. In addition, BCT‐100 showed an anticancer effect on H446 and H510A xenograft models by lowering arginine levels and inducing apoptosis. BCT‐100 is one type of pegylated recombinant human arginase. BCT‐100 showed an anticancer effect against small cell lung cancer through oxidative stress, apoptosis, and cell cycle arrest.

Background A majority of lung cancer patients are diagnosed at advanced stages. Although there is considerable evidence of the benefits of aerobic exercise and tai-chi for lung cancer patients, little is known about the comparative effectiveness of the 2 exercise modes in advanced lung cancer patients. Objectives To explore the feasibility and preliminary effects of aerobic exercise and tai-chi interventions on survival and well-being among advanced lung cancer patients. Methods In an assessor-blinded, exploratory randomized controlled trial, 30 advanced lung cancer patients were randomized to an aerobic exercise group, a tai-chi group (both attending 12-week, twice-weekly supervised sessions), or a self-management control group (receiving written exercise guidelines). The primary outcomes focused on feasibility including intervention completion, exercise adherence, and adverse events, while the secondary outcomes addressed preliminary effects and included 1-year survival, cancer symptoms (Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Score, Brief Fatigue Inventory), quality of life (EORTC QLQ-C30, QLQ-LC13), physical performance (6-minute walk test, up-and-go, sit-to-stand, 1-leg standing), activity levels (actigraph), and circadian rhythms (salivary cortisol). Results Intervention feasibility was established with a satisfactory completion rate at post-intervention for the aerobic exercise group (80%) and the tai-chi group (78%). The tai-chi group attained higher adherence than the exercise group in terms of attendance in supervised sessions (89% vs 75% of scheduled classes) and self-practice (225% vs 87% of the prescribed amount). Higher adherence to self-practice in the tai-chi group remained at the 6-month follow-up (81% vs 38% of the prescribed amount). No adverse event as a result of the intervention was reported. Effect-related outcomes did not show statistically significant changes in any group, except an improvement post-intervention in the up-and-go (−2.26, 95% CI: −4.04, −0.48) and sit-to-stand tests (4.52, 95% CI: 2.19, 6.85) in the aerobic exercise group. Conclusions The findings support the feasibility of aerobic exercise and tai-chi interventions in advanced lung cancer patients. A future study with a larger sample from multiple sites is recommended to confirm the comparative effects of the 2 exercise interventions relative to the self-management group and to enhance the generalizability of the findings.

Drug resistance is a major hurdle in the treatment of small cell lung cancer (SCLC). Previously we demonstrated the potential anticancer effect of pegylated arginase BCT-100 in SCLC cell lines and xenograft models. To facilitate future clinical application of BCT-100 in SCLC treatment, we elucidated the potential mechanisms that underlie acquired drug resistance to BCT-100. H446 and H526 SCLC cells were serially cultured in stepwise increasing concentrations of BCT-100 until stable BCT-100-resistant cell lines emerged (H446-BR and H526-BR). Compared with parent cells, H446-BR and H526-BR displayed stronger migration ability, anoikis resistance and EMT progression. Gene chip assay was employed to select three potential targets (CDH17, CNTN-1 and IGF2BP1). Silencing CNTN-1 rather than CDH17 or IGF2BP1 in H446-BR and H526-BR cells re-sensitized resistant cells to BCT-100 treatment and attenuated the epithelial–mesenchymal transition (EMT) phenotype. The AKT signaling pathway was activated in H446-BR and H526-BR cells accompanied by EMT progression, and AKT inhibitor LY294002 reversed the EMT progression in resistant cells.

Background: Inhalation of asbestos fibers is the most common cause of malignant pleural mesothelioma (MPM). In 2004, the United States Food and Drug Administration approved a combination of cisplatin with pemetrexed to treat unresectable MPM. Nonetheless novel treatment is urgently needed. The objective of this study is to report the combination effect of dichloroacetate (DCA) or niclosamide (Nic) Nic in MPM. Materials and methods: The effect of a combination of DCA and Nic was studied using a panel of MPM cell lines (H28, MSTO-211H, H226, H2052, and H2452). Cell viability was monitored by MTT assay. Glycolysis, oxidative phosphorylation, glucose, glycogen, pyruvate, lactate, citrate, succinate and ATP levels were determined by corresponding ELISA. Apoptosis, mitochondrial transmembrane potential, cell cycle analysis, hydrogen peroxide and superoxide were investigated by flow cytometry. Cell migration and colony formation were investigated by transwell migration and colony formation assays respectively. The in vivo effect was confirmed using 211H and H226 nude mice xenograft models. Results and conclusion: Cell viability was reduced. Disturbance of glycolysis and/or oxidative phosphorylation resulted in downregulation of glycogen, citrate and succinate. DCA and/or Nic increased apoptosis, mitochondrial transmembrane depolarization, G2/M arrest and reactive oxygen species. Moreover, DCA and/or Nic suppressed cell migration and colony formation. Furthermore, a better initial tumor suppressive effect was induced by the DCA/Nic combination compared with either drug alone in both 211H and H226 xenograft models. In H226 xenografts, DCA/Nic increased median survival of mice compared with single treatment. Single drug and/or a combination disturbed the Warburg effect and activated apoptosis, and inhibition of migration and proliferation in vivo . In conclusion, dichloroacetate and/or niclosamide showed a tumor suppressive effect in MPM in vitro and in vivo, partially mediated by disturbance of glycolysis/oxidative phosphorylation, apoptosis, ROS production, G2/M arrest, and suppression of migration and proliferation.

Advanced lung cancer patients suffer from deteriorated physical function, which negatively impacts physical and psychological health. As little is known about sleep and physical function in this population, this study aimed to examine the association between subjective and objective sleep parameters and physical function among them. 164 advanced lung cancer patients were included. Objective sleep was measured by actigraphy (measured on non-dominant wrist for 72 h), and subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Performance-based physical function was measured by Timed Up and Go Test (TUGT), 6-Minute Walk Test (6MWT), Sit-to-Stand Test, and One-leg Standing Test. Univariable and multivariable regression analyses were employed to examine the association between sleep and physical function. Total sleep time (TST) was significantly associated with the 6MWT (β = 0.259; 95% CI 0.120, 0.398; P < 0.001), TUGT (β = − 0.012; 95% CI = − 0.017, − 0.008; P < 0.001) and Sit-to-Stand Test (β = 0.027; 95% CI = 0.018, 0.035; P < 0.001) after adjustment for multiple covariates. PSQI global score was only significantly associated with TUGT (β = 0.140; 95% CI = 0.000, 0.280; P = 0.050) after adjustment for multiple covariates. Shorter sleep duration significantly predicted poorer physical performance in advanced lung cancer patients, and more attention is required for those with less than 4.3 h of sleep on average. Trial registration: ClinicalTrials.gov, NCT03482323. Registered 29 March 2018, https://clinicaltrials.gov/ct2/show/NCT03482323 ; ClinicalTrials.gov, NCT04119778. Registered 8 October 2019, https://clinicaltrials.gov/ct2/show/NCT04119778 .

Background/Objectives: Vaccination is a key preventive measure against pneumococcal disease, but uptake rates remain low in high-risk populations. Limited information exists on pneumococcal vaccine uptake in individuals with a history of pneumococcal disease. This study aims to assess pneumococcal vaccine uptake and the factors associated with it in patients hospitalized for pneumococcal disease, before and after hospitalization, across time periods before, during, and after the COVID-19 pandemic. Methods: Data for patients aged ≥18 years who were hospitalized for pneumococcal disease between 2015 and 2024 were extracted from the Hospital Authority’s territory-wide electronic medical record database. The uptake of pneumococcal vaccines in subgroups aged 18–64 years and ≥65 years, with and without risk conditions, both before and after hospitalization for pneumococcal disease, was assessed, followed by multivariate analyses of the factors associated with vaccination uptake by logistic regression models. Results: This study included 5517 patients hospitalized for pneumococcal disease. Prior to hospitalization, the vaccination uptake among the eligible patients was 20.5%, with only 8.1% fully vaccinated, despite the majority (87.9%) having previous hospitalizations (subgroup medians 3–9 times) or outpatient clinic visits (subgroup median 61–107 times). After discharge, during a median follow-up of 1.85 years, almost all the eligible patients (98.4%) received subsequent inpatient (subgroup medians 3–4 times) and outpatient (subgroup medians 21–28 times) care, but only 32.2% of the eligible patients received the vaccine. Factors associated with increased vaccine uptake post-discharge included age ≥75 years (OR 1.6), ≥10 subsequent hospitalizations (OR 2.1), and ≥10 subsequent clinic visits (OR 55.9). Vaccination rates within 12 months post-discharge were significantly lower in the patients hospitalized during the COVID-19 pandemic (3.5%) compared to the baseline (11.6%) and post-COVID-19 (6.6%) periods. Conclusions: The uptake of the pneumococcal vaccine before hospitalization for pneumococcal disease was low and continued to be suboptimal post-discharge. Numerous vaccination opportunities were missed in both the inpatient and outpatient settings. These findings indicate a need to improve vaccination strategies.

Background Malignant pleural mesothelioma (MPM) is a difficult-to-treat global disease. Pegylated arginase (BCT-100) has recently shown anti-tumor effects in hepatocellular carcinoma, acute myeloid leukemia and melanoma. This study aims to investigate the effects of PEG-BCT-100 in MPM. Methods A panel of 5 mesothelioma cell lines (H28, 211H, H226, H2052 and H2452) was used to study the in vitro effects of BCT-100 by crystal violet staining. The in vivo effects of BCT-100 were studied using 211H and H226 nude mice xenografts. Protein expression (argininosuccinate synthetase, ornithine transcarbamylase, cleaved PARP, cleaved caspase 3, cyclins (A2, D3, E1 and H), CDK4 and Ki67) and arginine concentration were evaluated by Western blot and ELISA respectively. Cellular localization of BCT-100 was detected by immunohistochemistry and immunoflorescence. TUNEL assay was used to identify cellular apoptotic events. Results Argininosuccinate synthetase was expressed in H28, H226, and H2452 cells as well as 211H and H266 xenografts. Ornithine transcarbamylase was undetectable in all cell lines and xenograft models. BCT-100 reduced in vitro cell viability (IC 50 values at 13–24 mU/ml, 72 h) across different cell lines and suppressed tumor growth in both 211H and H226 xenograft models. BCT-100 (60 mg/kg) significantly suppressed tumor growth ( p  < 0.01) with prolonged median survival ( p  < 0.01) in both xenograft models. Combining BCT-100 with pemetrexed or cisplatin conferred no additional benefits over single agents. Serum and intratumoral arginine levels were effectively decreased by BCT-100, associated with cytosolic accumulation of BCT-100 within tumor cells. Apoptosis (PARP cleavage in 211H xenografts; Bcl-2 downregulation, and cleavage of PARP and caspase 3 in H226 xenografts; positive TUNEL staining in both) and G1 arrest (downregulation of cyclin A2, D3, E1 and CDK4 in 211H xenografts; suppression of cyclin A2, E1, H and CDK4 in H226 xenografts) were evident with BCT-100 treatment. Furthermore, proliferative factor Ki67 was downregulated in BCT-100 treatments arms. Conclusions BCT-100 suppressed tumor growth with prolonged median survival partially mediated by intratumoral arginine depletion resulting in apoptosis and G1 arrest in mesothelioma xenograft models. The findings provide scientific evidence to support further clinical development of BCT-100 in treatment of MPM.

BackgroundAlthough bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking.MethodsA territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics.Results10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006–2.552, p value=0.047), 1.371 (95% CI 1.016–1.851, p value=0.039) and 1.238 (95% CI 1.001–1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE.ConclusionPatients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.

Background Elevation of systemic inflammatory markers were found to correlate with increased disease extent, reduced lung function and higher risk of future severe exacerbations in patients with bronchiectasis. Although a significant correlation of circulating hs-CRP levels with HRCT scores and resting oxygen saturation in patients with stable-state non-cystic fibrosis (CF) bronchiectasis was suggested, there is little data on the relationship between hs-CRP and the prognosis of bronchiectasis and a lack of data on the role of hs-CRP in predicting bronchiectasis exacerbation. Methods A prospective study was conducted on Chinese patients with non- CF bronchiectasis from 1st October to 31st December 2021. Baseline serum hs-CRP were obtained at stable-state. The follow-up period lasted for one year. Co-primary endpoints were the development of any bronchiectasis exacerbation and hospitalized bronchiectasis exacerbation. Results Totally 123 patients were included. Higher hs-CRP was associated with increased risk to develop any bronchiectasis exacerbation, adjusted odds ratio (aOR) of 2.254 (95% CI = 1.040–4.885, p  = 0.039), and borderline significantly increased hospitalized bronchiectasis exacerbation with aOR of 1.985 (95% CI = 0.922–4.277, p  = 0.080). Conclusion Baseline serum hs-CRP level at stable-state can predict risk of bronchiectasis exacerbation, which is reflecting chronic low-grade inflammation in bronchiectasis.

Cardiovascular–kidney–metabolic (CKM) syndrome is an increasingly recognized condition that highlights the interaction between three important medical co-morbidities. Whether the presence of CKM syndrome may increase the risk of in-hospital adverse outcomes in patients with pneumococcal pneumonia has not been investigated. We conducted a territory-wide retrospective study on adults hospitalized for pneumococcal pneumonia between 1 January 2016 and 31 December 2024 in Hong Kong. In-patient mortality, severe respiratory failure (SRF) and acute kidney injury (AKI) were compared among patients with cardiovascular–kidney–metabolic (CKM) syndrome at different stages. Subgroup analyses were performed in patients who have or have not received a pneumococcal vaccine. In total, 2192 patients were hospitalized for pneumococcal pneumonia in the study period, with 1005 (45.8%), 373 (17.0%), 684 (31.2%) and 130 (5.9%) at stage 0–1, 2–3, 4a and 4b CKM syndrome. A higher stage of CKM syndrome was associated with increased risks of death during index admission, SRF and AKI. The adjusted odds ratios (aOR) for CKM stage 4a and 4b for death during index admission were 1.82 (95% CI 1.25–2.64) and 10.92 (95% CI 6.82–17.49) respectively (p = 0.002 and <0.001). The aOR for SRF for CKM stage 2–3, 4a and 4b were 1.43 (95% CI 1.01–2.03), 1.88 (95% CI 1.39–2.54) and 28.42 (95% CI 16.92–47.74) respectively (p = 0.042, <0.001 and <0.001). The aOR for AKI for CKM syndrome stage 2–3, 4a and 4b were 2.25 (95% CI 1.53–3.29), 3.00 (95% CI 2.14–4.22) and 4.30 (95% CI 2.69–6.88) (p < 0.001 for all). Subgroup analysis showed consistent results among those who have or have not received a pneumococcal vaccine within the 12 months preceding the index admission date. CKM syndrome, especially at a higher stage, constitutes an independent risk factor for severe in-hospital outcomes in adults hospitalized for pneumococcal pneumonia.