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BACKGROUND/AIMS: At present, there are relatively few reports on the treatment consisting of transarterial chemoembolization (TACE) combined with lenvatinib, and there is no unified conclusion on the curative effect. The objective of this research was to assess the efficacy and safety of combining TACE with lenvatinib for the treatment of unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: This study was a retrospective analysis of the patient's medical records. In this study, 249 patients (uHCC) in our hospital from 2020 to 2021 were divided into 2 groups, including the TACE-alone group (198 patients received TACE alone) and the TACE-LEN group (51 patients were treated with TACE combined with lenvatinib). According to the propensity score matching method, there were TACE-LEN group (51 patients) and TACE-alone group (51 patients). With the help of surgical experts, the overall survival (OS), progression-free survival (PFS), and tumor response (according to mRECIST) of the 2 groups were sorted and recorded, and then analyzed. Survival curves were established, the prognostic factors of OS and PFS were analyzed by univariate and multivariate analyses, and the independent prognostic factors were recorded. The adverse reactions of patients after treatment were recorded. RESULTS: The 1-year and 2-year OS rates were 50.98% and 19.48% for the TACE-LEN group, 27.45% and 8.55% for the TACE-alone group (P = .042), respectively. The PFS of patients in the TACE-LEN group was also longer (1-year PFS rate: 25.49% vs. 11.76%, 2-year PFS rate: 19.17% vs. 5.88%; P = .0069). The disease control rate (68.63% vs. 49.10%, P = .044) of the TACE-LEN group was significantly higher. In the subgroup analysis, the OS of the TACE-LEN group was better than TACE-alone group in patients with Barcelona Clinic Liver Cancer stage C (1-year OS rate: 44.44% vs. 17.14%, 2-year OS rate: 8.67% vs. 0%; P = .009). Factor analysis concluded that serum alkaline phosphatase and treatment protocol (TACE-LEN vs. TACE) were independent influencing factors of OS. The most common treatment-related AEs included decreased albumin (n = 28, 54.9%), hypertension (n = 23, 45.1%), elevated aspartate transaminase (n = 21, 41.2%) and elevated total bilirubin (n = 18, 35.2%) in TACE-LEN group. CONCLUSION: Compared with TACE monotherapy, TACE combined with lenvatinib effectively prolonged the OS time with a controllable safety profile for patients with uHCC.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Estudos Retrospectivos , Feminino , Masculino , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Resultado do Tratamento , Terapia Combinada , Pontuação de PropensãoRESUMO
Background: To evaluate the clinical research related to the level and integrity of circulating free DNA (cfDNA) in the plasma of patients with multiple myeloma (MM). Methods: The plasma samples of 56 patients with newly diagnosed MM and 60 healthy volunteers were collected. ALU247 fragment and ALU115 fragment were used as target genes, and quantitative polymerase chain reaction (qPCR) was used to assess the plasma of the patient and healthy control groups. The cfDNA level in MM was analyzed, and the ALU247/ALU115 ratio was used to calculate the integrity of cfDNA. The correlation between the cfDNA level and integrity and the clinical characteristics of patients with primary MM was analyzed, and their value in efficacy monitoring and prognostic evaluation was evaluated. Results: The plasma concentrations of ALU247 and ALU115 and the integrity of cfDNA in patients with primary MM were significantly higher than those in the healthy controls (P<0.05). The ALU247 fragment concentration was markedly correlated with the Durie-Salmon (D-S), International Staging System (ISS), and Revised-International Staging System (R-ISS) stages (P<0.05). After three courses of induction chemotherapy, the levels of ALU247, ALU115, and cfDNA integrity in both groups were lower than those before chemotherapy (P<0.05). Patients with curative effects of CR, sCR, and VGPR were classified into the ≥ very good partial response (VGPR) group (n=38), while those with curative effects of PR and SD were allocated into the
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As is known, hepatic stellate cells (HSCs) activation contributes to liver cirrhosis. This study aims to find out the acting mechanisms of miR-454 inhibiting the activation and proliferation of hepatic stellate cells. The expression of Col1A1, α-smooth muscle actin (α-SMA) and Wnt10a were determined by western blot, and the miR-454 level was determined by quantitative real-time PCR in this study. We took two objects as experiment subjects, one was liver cirrhosis rats, and the other was transforming growth factor (TGF)-ß1-stimulated HSC-T6 cells. After activated with TGF-ß1 and transfected with microRNA-454 mimic, separately or successively, the changes on the Col1A1 and α-SMA expression, HSC proliferation, miR-454 level and Wnt10a expression were examined in HSC-T6 cells, respectively. Interaction between miR-454 and Wnt10a was evaluated with dual luciferase reporter assay. MiR-454 expression was down-regulated in tissues of liver cirrhosis rats. TGF-ß1 caused the down-regulation of the miR-454 in HSC-T6 cells. MiR-454 inhibited the activation and proliferation of HSC-T6 cells. Wnt10a had a targeting relationship with miR-454. TGF-ß1 promoted HSC-T6 activation and proliferation via down-regulating miR-454 expression, which further up-regulated Wnt10a expression. MiR-454 mimic inhibited cirrhosis progression in liver cirrhosis rats. MiR-454 can inhibit the activation and proliferation of HSCs via suppressing the expression of Wnt10a, to restrain liver cirrhosis.
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Proliferação de Células , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , MicroRNAs/metabolismo , Proteínas Wnt/metabolismo , Animais , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Regulação da Expressão Gênica , Células Estreladas do Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Ratos , Fator de Crescimento Transformador beta1/metabolismoRESUMO
PURPOSE: To investigate whether triphasic CT with a simplified Patlak plot can be used in clinical practice for the estimate of split kidney glomerular filtration rate (SKGFR). MATERIALS AND METHODS: The animal experiment included 15 rabbits that underwent 40 dynamic contrast-enhanced CT scans of the kidneys with 1.5 s time interval. Patlak-derived SKGFR was obtained using standard forty-point, two-point (unenhanced phase, arterial phase t α, and portovenous phase t ß), and a modified two-point (MTP) (unenhanced, t α, t ß, and a virtual t τ [t τ = (t α + t ß)/2]) image data, respectively. The MTP-Patlak plot approach was then validated in 13 patients who underwent a triphasic renal contrast-enhanced CT examination. SKGFR measured by 99mTc-DTPA clearance was as a standard reference. RESULTS: MTP-Patlak significantly reduced input function errors than two-point Patlak (21.1 ± 16.2 % vs 30.8 ± 15.2 %, p < 0.01) and showed good concordance with standard Patlak for measurement of SKGFR in animal experiment (1.20 ± 0.38 mL/g/min vs 1.51 ± 0.43 mL/g/min; linear correlation coefficient r = 0.87, p < 0.001). Human study showed that mean SKGFR was 45.7 mL/min (range, 26.5-86.2 mL/min) obtained from 99mTc-DTPA, and 38.2 mL/min (range, 18.6-79.3 mL/min) obtained from triphasic CT using MTP-Patlak plot. Linear correlation between the two methods was r = 0.75 (p < 0.01). The mean difference between SKGFRs as determined with the two methods was 7.4 ± 9.0 mL/min. CONCLUSION: The MTP-Patlak approach, featured with simplicity, is feasible in a clinically indicated CT examination for the evaluation of split renal function.