MG 46

TACE was performed according to our previously reported protocol [16 (link)]. Chemolipiodolization was performed using 50 mg of epirubicin (pharmorubicin; Pfizer, Wuxi, Jiangsu, China), 50 mg of lobaplatin (Hainan Changan International Pharmaceutical Co. Ltd., Haikou, Hainan, China), and 6 mg of mitomycin C (Zhejiang Hisun Pharmaceutical Co. Ltd., Taizhou, Zhejiang, China) mixed with 10 mL of lipiodol (Lipiodol Ultra-Fluide; Guerbet Laboratories, Aulnay Sous Bois, Paris, France). If necessary, up to 20 mL of additional pure lipiodol was injected. The injection was stopped when stasis of blood flow in the target artery was observed. Subsequently, embolization was performed with the injection of polyvinyl alcohol particles that were 300–500 μm in diameter through the catheter to reach stasis in the tumor-feeding artery. Repeated TACE was performed at intervals of 6 weeks.
In the HAIC group, patients were treated using a 3-week cycle regimen. A catheter was advanced into the hepatic artery according to our previously reported protocol [16 (link)]. A microcatheter was selectively placed into the feeding arteries of the tumor. The gastroduodenal artery was occluded by a coil when necessary. Then, the microcatheter was connected to the artery infusion pump to administer the following treatment: OXA, 85 mg/m² intra-arterial infusion on day 1; LV, 400 mg/m² intra-arterial infusion on day 1; and 5-FU, 400 mg/m² bolus infusion on day 1 and 2400 mg/m² continuous infusion over 46 h. After HAIC was completed, the indwelling catheter and the sheath were removed, and manual compression was performed to achieve hemostasis.
HAIC and TACE were discontinued when disease progression (including vascular invasion or the development of extrahepatic spread) or intolerable AEs occurred or when the patient was eligible for another treatment (surgical resection) or withdrew consent. Additionally, the study treatment was suspended when the following conditions occurred: technical difficulty in repeating the treatment (stenosis or occlusion of the tumor-feeding artery or an artery only supplied by the extrahepatic collateral arteries) or unsuitable characteristics (neutrophil count < 1200/μL, platelet count < 60,000/μL, total bilirubin > 30 mmol/L, or albumin < 3.0 mg/dL). The study treatment was stopped if no recovery occurred after a 30-day delay.
If the study treatment was discontinued, the following treatment was defined as subsequent treatment. The subsequent treatment decisions of both groups would be made according to the same protocol by the same multidisciplinary team, based on the tumor burden, liver function, and the patient’s request. Basically, hepatic resections were performed on patients whose tumor shrank to be resectable. For patients with tumor progression without contraindications to TACE, repeating TACE was recommended. For patients whose residual tumors could not be embolized due to technical problems, radiofrequency ablations were used to destroy residual tumors when it was feasible. Conservative treatments were given to patients with terminal HCC, Child–Pugh C liver function, or Eastern Cooperative Oncology Group (ECOG) score > 2 [32 (link)].

Based on the International Obesity Task Force[24 ], convened by the World Health Organization, a subject with BMI ≥ 30.0 kg/m² was defined as obese. The WC measurements were used to determine the extent of central adiposity, with cut-off points of ≥ 102 cm in men and ≥ 88 cm in women[25 (link)]. Participants were classified as having elevated blood pressure if they reported taking anti-hypertensive medications and/or had SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg [26 (link)].Participants were classified as diabetics if they reported taking anti-diabetic medications and/or had FPG ≥ 126 mg/dl [27 (link),28 (link)]. Subjects with lipid disorder were defined as having at least one of the following anomalies: TC ≥ 190 mg/dl, TG ≥ 150 mg/dl, LDL-C ≥ 115 mg/dl, and HDL-C < 40 mg/dl for men and < 46 mg/dl for women [29 (link)], and/or taking hypo-lipid medications. Smoking status was evaluated by the self-reported questionnaire. Each participant was classified as current smoker, ex-smoker or non-smoker. Current regular smokers were those who smoked at least one cigarette per day. Current occasional smoker were those who smoked less than one cigarette per day. The present study specifically focused on 5 distinct CVRF, respectively, obesity, hypertension, diabetes mellitus, lipid disorder, and current smoking. The metabolic syndrome (MS) was succinctly presented according to the simplest and most used R-ATP III definition[30 (link)]; a participants is defined as having the MS when three or more of the following criteria are met: 1) WC ≥ 102 cm for men and ≥ 88 cm for women; 2) raised concentration of TG ≥ 150 mg/dl or specific treatment for this lipid anomaly; 3) reduced concentration of HDL-C < 40 mg/dl for men and < 50 mg/dl for women or specific treatment for this lipid anomaly; 4) SBP was ≥ 130 mmHg, or DBP ≥ 85 mmHg or treatment of previously diagnosed hypertension; 5) FPG level ≥100 mg/dl or use of medication for hyperglycemia.

COE-3 is a full-length
monoclonal antibody of the IgG1 subtype, with a non-glycosylated molecular
weight (MW) of approximately 146 kDa. Its Fc has a MW of ∼50
kDa and each of its Fabs has a MW of ∼47 kDa. COE-3 was provided
by AstraZeneca at 46.4 mg/mL in 25 mM histidine/histidine hydrochloride
buffer (HIS) with 7% w/v sucrose. COE-3 was cleaved into its constituent
fragments by digestion with papain and then separated using cation
exchange chromatography. The fragments were then exchanged into phosphate
buffer and re-concentrated using ultrafiltration and spin filtration
to 47.74 mg/mL for Fc and 50.4 mg/mL for Fab. Proteins were directly
diluted into measurement buffers of the desired isotopic contrast.
All measurements were made in pH 5.5 HIS buffer at an ionic strength
of 25 mM and at a temperature of 20 ± 3 °C. The full sequence
for COE-3 has been published in previous work.^{9 (link)}