ANGPTL4 T266M variant is associated with reduced cancer invasiveness.

Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form an N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes. In this study, we compared the characteristics of tumors with and without wild-type (wt) cANGPTL4 and tumors with cANGPTL4 bearing the T266M mutation (T266M cANGPTL4). We found that T266M cANGPTL4 bound to integrin α5ß1 with a reduced affinity compared to wt, leading to weaker activation of downstream signaling molecules. The mutant tumors exhibited impaired proliferation, anoikis resistance, and migratory capability and had reduced adenylate energy charge. Further investigations also revealed that cANGPTL4 regulated the expression of Glut2. These findings may explain the differences in the tumor characteristics and energy metabolism observed with the cANGPTL4 T266M mutation compared to tumors without the mutation.

Do advanced cancer patients and their caregivers agree on preferred place of patient's death?-a prospective cohort study of patient-caregiver dyads.

BACKGROUND: Greater patient-caregiver concordance for preferred place of death can increase the chances of patients dying at their preferred place, thus improving quality of life at end-of-life (EOL). We aimed to assess changes in and predictors of patient-caregiver concordance in preference for home death at EOL during the last 3 years of life of patients with advanced cancer. METHODS: We used data from the Cost of Medical Care of Patients with Advanced Serious Illness in Singapore (COMPASS) cohort study of patients with stage IV solid cancer. We interviewed patients and their caregivers every 4 months to assess their preference for home death (for patient), and patient (symptom burden, inpatient usage, financial difficulties) and caregiver (psychosocial distress, spiritual wellbeing, competency and perceived lack of family support) characteristics. We used data from patients' last 3 years of life. We used multivariable multinomial logistic regressions to predict dyad concordance for preference for home death. RESULTS: A total of 227 patient-caregiver dyads were analyzed. More than half of the patient-caregiver dyads observations were concordant in their preference for home death (54%). Concordance for home death declined closer to death (from 68% to 44%). Concordant dyads who preferred home death were less likely to include older patients [relative risk ratio, 0.97; P=0.03]. Dyads who preferred a non-home death (hospital, hospice, nursing home, unsure or others) were more likely to include patients with greater symptom burden (1.08; P=0.007) and with spousal caregivers (2.59; P=0.050), and less likely to include caregivers with greater psychosocial distress (0.90; P=0.003) and higher spiritual wellbeing (0.92; P=0.007). CONCLUSIONS: This study provides evidence of the dynamic changes in preference for home death among patient-caregiver dyads during last 3 years of patients' life. Understanding the EOL needs of older patients, optimizing home-based symptom control and better caregiver support are recommended to increase likelihood of dyad concordance for home death.

Clinical and economic evaluation of a surveillance protocol to manage hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

STUDY OBJECTIVE: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. DESIGN: Prospective, single-arm study. SETTING: National Cancer Centre, Singapore. PATIENTS: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. INTERVENTION: Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. MEASUREMENTS: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. MAIN RESULTS: A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. CONCLUSIONS: The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

A study protocol for HEalth-Related quality of life-intervention in survivors of Breast and other cancers experiencing cancer-related fatigue using TraditionAL Chinese Medicine: the HERBAL trial.

BACKGROUND: Cancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors. METHODS: This is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated. DISCUSSION: Efficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04104113 . Registered on 26 September 2019.