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1.
Ann Surg Oncol ; 30(5): 2782-2790, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36178565

RESUMO

BACKGROUND: Combined treatment with tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies showed high anti-tumor efficacy and made conversion resection possible for patients with unresectable hepatocellular carcinoma (HCC). However, long-term survival has not been reported. METHODS: A cohort of consecutive patients who received combined TKI/anti-PD-1 antibodies as first-line treatment for initially unresectable HCC at the authors' hospital between August 2018 and September 2020 was eligible for this study. Patients who were responding to systemic therapy and met the criteria for hepatectomy underwent liver resection with curative intention. The study also investigated the association of clinical factors with successful conversion resection and postoperative recurrence. RESULTS: The study enrolled 101 patients including 24 patients (23.8 %) who underwent R0 resection a median of 3.9 months (interquartile range: 2.5-5.9 months) after initiation of systemic therapy. Patients with an Eastern cooperative oncology group performance status of 0, fewer intrahepatic tumors, or a radiographic response to systemic therapy were more likely to be able to receive curative resection. After a median follow-up period of 21.5 months, hepatectomy was independently associated with a favorable overall survival (hazard ratio [HR], 0.050; 95 % confidence interval [CI], 0.007-0.365; P = 0.003). For the 24 patients who underwent surgery, the 12-month recurrence-free survival and overall survival rates were respectively 75% and 95.8%. Achieving a pathologic complete response (n = 10) to systemic therapy was associated with a favorable recurrence-free survival after resection, with a trend toward significance (HR, 0.345; 95% CI, 0.067-1.785; P = 0.187). CONCLUSIONS: Selected patients with initially unresectable HCC can undergo hepatectomy after systemic therapy with combined TKI/anti-PD-1 antibodies. In this study, conversion resection was associated with a favorable prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Prognóstico
2.
Exp Cell Res ; 367(1): 81-88, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29571949

RESUMO

Hypoxia is associated with the progression of hepatocellular carcinoma through promotion of spontaneous metastasis but the mechanism remains unclear. Here, we hypothesis that tumor cell-derived HMGB1 orchestrates macrophages infiltration and promotes metastasis of HCC via enhancing macrophage-secreted IL-6 under hypoxia. HMGB1 expression was robustly exacerbated in tumors of HCC patients with PVTT. Meanwhile, hypoxia exposure gave rise to HMGB1 expression in hepatoma cells of human and mouse in a HIF-1α-dependent manner and subsequently induced the infiltration and reprogramming of macrophages to augment the expression of Il-6. Further study demonstrated macrophage-derived IL-6 enhanced the invasiveness and metastasis of murine HCC cells. Therefore, our study provides a novel understanding of the relationship between tumor cells and tumor associated macrophages (TAMs) in the context of hypoxia.


Assuntos
Carcinoma Hepatocelular/patologia , Proteína HMGB1/metabolismo , Interleucina-6/metabolismo , Neoplasias Hepáticas/patologia , Macrófagos/fisiologia , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Feminino , Proteína HMGB1/genética , Células Hep G2 , Humanos , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Vasc Interv Radiol ; 27(10): 1577-83, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27103146

RESUMO

PURPOSE: To evaluate the safety and efficacy of microwave (MW) ablation combined with transarterial chemoembolization in a single stage for the treatment of large (≥ 5 cm) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March 2013 to January 2015, 66 patients (54 men and 12 women; mean age, 54 y; range, 29-83 y) with 72 large HCC lesions were included in this study. Eighteen (27.3%) had Barcelona Clinic Liver Cancer class B disease, and 48 (72.7%) had class C disease. Seventy-nine percent of patients (n = 52) had hepatitis B virus infection. The average tumor size was 9.0 cm ± 3.9, ranging from 5 to 19 cm. MW ablation was performed under ultrasound guidance, immediately followed by chemoembolization. Local tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: The technique was successfully performed in all patients. Complete response (CR) was achieved in 28 cases (42.4%), and partial response (PR) was achieved in 34 cases (51.5%) at 1 month after the procedure. The objective response rate (ie, CR plus PR) was 93.9%. Median PFS and OS times were 9 months and 21 months, respectively. The 6-, 12-, and 18-month OS rates were 93.9%, 85.3%, and 66.6%, respectively. Hemorrhage was detected in three patients and arteriovenous fistula in two patients after MW ablation; all were promptly treated with embolization. There were no liver abscesses, bile-duct injuries, or other major procedure-related complications. CONCLUSIONS: MW ablation immediately followed by chemoembolization is safe and effective in the treatment of large HCC lesions.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Quimioterapia Adjuvante , China , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Ultrassonografia de Intervenção
5.
Nat Commun ; 15(1): 621, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245530

RESUMO

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Compostos de Fenilureia , Quinolinas , Humanos , Oxaliplatina/uso terapêutico , Gencitabina , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Linfócitos T CD8-Positivos , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Proteínas Reguladoras de Apoptose , Receptores Depuradores
6.
BMC Gastroenterol ; 13: 53, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-23530688

RESUMO

BACKGROUND: Three-dimensional (3D) whole-liver perfusion magnetic resonance (MR) imaging with parallel imaging, a novel imaging method to characterize tumor vascularization in vivo, has recently been applied to comprehensively image perfusion changes in large tumors. Coupled with new perfusion software, this technique enables motion correction, registration, and evaluation of perfusion MR parameters. The purpose of this study was to assess the feasibility of 3D whole-liver perfusion MR, for imaging hepatocellular carcinoma (HCC) and colorectal hepatic metastases (CRHM). METHODS: 26 patients with hepatic tumors (10 HCC; 16 CRHM) were subjected to 3D whole-liver perfusion MR with a temporal resolution of 3.7 seconds. The following estimated perfusion parameters were measured: the volume transfer constant K(trans) (min(-1)); the volume (V(e)) of extravascular extracellular space (EES) per volume unit of tissue; and the flux rate constant between EES and plasma K(ep) (min(-1)). Statistical analysis was conducted to investigate inter-observer characteristics and significance of the measured parameters. RESULTS: Inter-observer agreement analysis (95% limits of agreement) yielded a mean difference of -0.0048 min(-1) (-0.0598 ~ 0.0502) for K(trans), -0.0630 ml (-0.5405 ~ 0.4145) for V(e), and -0.0031 min(-1) (-0.0771 ~ 0.0709) for K(ep) respectively. When comparing images from patients with HCC vs. CRHM, significant differences were seen for the mean K(trans) (p = 0.017), but not for V(e) (p = 0.117) or K(ep) (p = 0.595). CONCLUSION: Herein we show that 3D whole-liver MR perfusion imaging with semi-automatic data analysis is feasible and enables the reliable quantitative evaluation of the perfusion parameters for HCCs and CRHMs.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Angiografia por Ressonância Magnética , Idoso , Neoplasias Colorretais/patologia , Meios de Contraste/farmacocinética , Estudos de Viabilidade , Feminino , Gadolínio DTPA/farmacocinética , Humanos , Imageamento Tridimensional , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estatísticas não Paramétricas
7.
BMC Cancer ; 12: 263, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22721173

RESUMO

BACKGROUND: The long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC. METHODS: Between June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded. RESULTS: The median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9-32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9-25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed. CONCLUSION: TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.


Assuntos
Antineoplásicos/administração & dosagem , Benzenossulfonatos/administração & dosagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Piridinas/administração & dosagem , Adulto , Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Resultado do Tratamento
8.
Front Oncol ; 12: 1086095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36741718

RESUMO

Objective: To evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT). Patients and methods: From December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups. Results: The mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p < 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p < 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028). Conclusion: This interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.

9.
BJS Open ; 6(5)2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36125345

RESUMO

BACKGROUND: Combination conversion therapies afforded curative surgery chance for initially unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the conversion rate and clinical outcomes of a first-line conversion regimen of lenvatinib combined with transarterial chemoembolization (TACE) plus immunotherapy for initial uHCC by interpreting real-world data. METHODS: Conversion therapy data of patients with uHCC from November 2018 to January 2021 were analysed. The regimens included triple combination therapy (t-CT: lenvatinib, TACE, plus toripalimab) and dual combination therapy (d-CT: lenvatinib plus TACE). Another study population diagnosed with hepatocellular carcinoma of macrovascular invasion disease were included as the upfront surgery cohort. Treatment responses and conversion rate were primary outcomes. Survival and adverse events were analysed. RESULTS: Fifty-one patients receiving t-CT (n = 30) and d-CT (n = 21) were enrolled. Higher overall response rates (76.7 per cent versus 47.6 per cent, P = 0.042) and disease control rates (90.0 per cent versus 57.1 per cent, P = 0.042) were observed via t-CT than d-CT. Both median overall survival and event-free survival were not reached in the t-CT cohort. A higher rate of curative conversion resection was achieved through t-CT than d-CT (50.0 per cent versus 19.0 per cent, P = 0.039). The disease-free survival of patients undergoing conversion resection in the t-CT cohort (n = 15) was higher than that in the upfront surgery cohort (n = 68, P = 0.039). Both t-CT and d-CT regimens were tolerable. CONCLUSIONS: Better treatment responses and conversion rate for patients with uHCC were obtained with first-line t-CT. Neoadjuvant t-CT before surgery should be recommended for patients with macrovascular invasion.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Compostos de Fenilureia , Quinolinas , Resultado do Tratamento
10.
Zhonghua Zhong Liu Za Zhi ; 33(7): 535-9, 2011 Jul.
Artigo em Zh | MEDLINE | ID: mdl-22093634

RESUMO

OBJECTIVE: To evaluate the therapeutic effect of endovascular placement of iodine-125 seed strand and stent combined with transcatheter arterial chemoembolization (TACE) to treat hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein (MPVTT). METHODS: Fifty patients with HCC complicated by MPVTT were enrolled into this study. There were 46 men and 4 women with a mean age of 53.9 years. TACE was performed after the iodine-125 seed strand and self-expandable stent placement in the obstructed segment of the main portal vein (MPV). RESULTS: Technical success rate was 100% for placement of iodine-125 seed strand and stent in the target segment of MPV. No serious procedure-related complications occurred. The mean follow-up duration was 208.5 d. The mean and median survival time was 370.1 d and 223.0 d, respectively. The 90-, 180-, 360-day cumulative survival rates were 97.5%, 59.3%, and 38.4%, respectively. The mean and median patent time of stent was 524.2 d and 407.4 d, respectively. The 90-, 180-, 360-day cumulative patency rates of stent were 94.9%, 75.2%, and 64.5%, respectively. CONCLUSION: Endovascular placement of iodine-125 seed strand and stent combined with TACE is an effective therapy for HCC with tumor thrombus in the main portal vein.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Hepáticas/terapia , Stents , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Veia Porta/patologia , Taxa de Sobrevida
11.
Liver Cancer ; 10(4): 320-329, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34414120

RESUMO

BACKGROUND: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. METHODS: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. RESULTS: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4-8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8-15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. CONCLUSIONS: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

12.
Clin Transl Med ; 10(3): e137, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32702202

RESUMO

BACKGROUND: High rates of postoperative tumor recurrence contribute to poor outcome in hepatocellular carcinoma (HCC). Here, we investigated whether circulating tumor cells (CTCs) status can predict the benefit of adjuvant transcatheter arterial chemoembolization (TACE) in patients with HCC. METHODS: The retrospective study enrolled 344 HCC patients with preoperative CTCs analysis. Clinical outcomes including recurrence and survival were compared between those who received and who did not receive adjuvant TACE. Similar comparisons were made for patients stratified according to CTC status (CTC-negative [CTC = 0], n = 123; CTC-positive [CTC ≥ 1], n = 221). Propensity score matching (PSM) strategy was adopted to offset differences between two groups. RESULTS: In the study cohort as a whole or in CTC-negative cohort, there were no observable differences in overall survival (OS) or time to recurrence (TTR) between TACE and control group (P > .05). In CTC-positive patients, PSM generated 64 patient pairs, and patients with adjuvant TACE had significantly better clinical outcomes (OS: not reached vs 36.4 months, P < .001; TTR: 45.8 vs 9.8 months, P < .001). Adjuvant TACE significantly reduced early recurrence (≤2 years) (64.1% vs 31.7%, P < .001) in CTC-positive patients. Notably, adjuvant TACE influenced TTR and OS even in subgroups of CTC-positive patients with low risk of recurrence according to traditional evaluation. CONCLUSIONS: Preoperative CTC status could serve as an indicator for the administration of adjuvant TACE in HCC patients. Adjuvant TACE benefits CTC-positive HCC patients mainly by reducing early recurrence.

13.
Clin Chim Acta ; 511: 67-74, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979338

RESUMO

AIMS: The present study aimed to determine the prognostic significance of soluble Programmed Death-ligand 1 (sPD-L1) in hepatocellular carcinoma (HCC) patients undergoing transcatheter arterial chemoembolization (TACE). METHODS: We treated 114 HCC patients with TACE from 2012 to 2013 and determined their sPD-L1 levels by enzyme-linked immunosorbent assay. We evaluated prognosis according to mRESIST criteria and analyzed prognostic values by Cox regression and Kaplan-Meier analysis. We further evaluated correlations between sPD-L1 level and inflammatory status, as well as immunosuppressive environment. RESULTS: sPD-L1 levels were significantly increased in patients who developed HCC progression (P = 0.002) and death (P < 0.001). Patients with higher pre-treatment sPD-L1 levels had a significantly shorter time to progression (10.50 vs. 18.25 months, P = 0.001) and decreased overall survival (16.50 vs. 28.50 months, P = 0.003). Importantly, sPD-L1 levels positively correlated with SII (r = 0.284, P = 0.002), sIL-2R (r = 0.239, P = 0.010), IL-10 (r = 0.283, P = 0.002), HBV-DNA loads (r = 0.229, P = 0.014), and CRP (r = 0.237, P = 0.011). Moreover, high sPD-L1 levels had increased numbers of Treg cells (FOXP3+; P = 0.026), Macrophage cells (CD68+; P = 0.014), and M2-Macrophage cells (CD163+; P = 0.026) CONCLUSIONS: sPD-L1 level is a prognostic indicator of poor outcomes after TACE. High sPD-L1 might reflect increased immune activation in an immunosuppressive environment that hindered anti-tumor response activity.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Hepatocelular/terapia , Humanos , Terapia de Imunossupressão , Neoplasias Hepáticas/terapia , Prognóstico
14.
World J Gastroenterol ; 14(38): 5893-9, 2008 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-18855990

RESUMO

AIM: To explore the diffusion gradient b-factor that optimizes both apparent diffusion coefficient (ADC) measurement and contrast-to-noise (CNR) for assessing tumor response to transarterial chemoembolization (TACE) in a rabbit model. METHODS: Twelve New Zealand white rabbits bearing VX2 tumors in the liver were treated with TACE. Diffusion-weighted imaging (DWI) with various b values was performed using the same protocol before and 3 d after treatment with TACE. ADC values and CNR of each tumor pre- and post-treatment with different b factors were analyzed. Correlation between ADC values and extent of necrosis in histological specimens was analyzed by a Pearson's correlation test. RESULTS: The quality of diffusion-weighted images diminished as the b value increased. A substantial decrease in the mean lesion-to-liver CNR was observed on both pre- and post-treatment DW images, the largest difference in CNR pre- and post-treatment was manifested at a b value of 1000 s/mm(2) (P = 0.036 ). The effect of therapy on diffusion early after treatment was shown by a significant increase in ADCs (P = 0.007), especially with large b factors (>= 600 s/mm(2)). The mean percentage of necrotic cells present within the tumor was 76.3%-97.5%. A significant positive correlation was found between ADC values and the extent of necrosis with all b values except for b200, a higher relative coefficient between ADC values and percentage of necrosis was found on DWI with b1000 and b2000 (P = 0.002 and 0.006, respectively). CONCLUSION: An increasing b value of up to 600 s/mm(2) would increase ADC contrast pre- and post-treatment, but decrease image quality. Taking into account both CNR and ADC measurement, diffusion-weighted imaging obtained with a b value of 1000 s/mm(2) is recommended for monitoring early hepatic tumor response to TACE.


Assuntos
Quimioembolização Terapêutica , Imagem de Difusão por Ressonância Magnética , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/terapia , Modelos Biológicos , Animais , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Neoplasias Hepáticas Experimentais/irrigação sanguínea , Masculino , Necrose , Valor Preditivo dos Testes , Coelhos , Fatores de Tempo , Resultado do Tratamento
16.
Technol Cancer Res Treat ; 17: 1533033818788529, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30045673

RESUMO

OBJECTIVE: To investigate the safety and efficacy of radiofrequency ablation combined with transarterial chemoembolization in patients with specially located small hepatocellular carcinoma. MATERIALS AND METHODS: Between March 2014 and March 2017, a total of 26 patients with 26 lesions (10 perivascular, 6 subdiaphragmatic, 5 subcapsular, 5 perivascular, and subdiaphragmatic location; mean diameter 2.12 (0.62) cm), who received radiofrequency ablation-transarterial chemoembolization treatment, were retrospectively analyzed. Local tumor response was assessed by computed tomography/magnetic resonance imaging 1 month after the procedure. Tumor-free survival was also assessed according to the modified Response Evaluation Criteria in Solid Tumors. Complications were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Complete response was achieved in all patients 1 month after the procedure. During a median follow-up duration of 16.76 months (95% confidence interval: 7.78-25.73 months), local tumor recurrence occurred in 2 patients and new intrahepatic lesions developed in 7 patients. The 1-, 2-, and 3-year cumulative local tumor progression rates were 3.84%, 7.69%, and 7.69%, respectively. The median tumor-free survival duration was 21.96 months (95% confidence interval: 17.58-26.34 months). The 1-, 2-, and 3-year tumor-free survival rates were 67.4%, 46.1%, and 39.3%, respectively. CONCLUSION: The radiofrequency ablation-transarterial chemoembolization combination therapy appears to be safe and effective and might be a treatment option for specially located small hepatocellular carcinoma lesions that have a risk of incomplete ablation or major complications.


Assuntos
Carcinoma Hepatocelular/radioterapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Ablação por Radiofrequência/métodos , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Ablação por Radiofrequência/efeitos adversos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Chem Biol ; 13(6): 575-85, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16793515

RESUMO

The biosynthetic gene cluster for chlorothricin (CHL) was localized to a 122 kb contiguous DNA from Streptomyces antibioticus DSM 40725, and its involvement in CHL biosynthesis was confirmed by gene inactivation and complementation. Bioinformatic analysis of the sequenced 111.989 kb DNA region revealed 42 open reading frames, 35 of which were defined to constitute the CHL gene cluster. An assembly model for CHL biosynthesis from D-olivose, 2-methoxy-5-chloro-6-methylsalicyclic acid, and chlorothricolide building blocks was proposed. This work represents cloning of a gene cluster for spirotetronate antibiotic biosynthesis and sets the stage to investigate the unusual macrolide biosynthesis including tandem Diels-Alder cyclizations, Baeyer-Villiger oxidation, and incorporation of an enoylpyruvate unit.


Assuntos
Aminoglicosídeos/genética , Aminoglicosídeos/metabolismo , Antibacterianos/biossíntese , Família Multigênica/genética , Sequência de Aminoácidos , Aminoglicosídeos/química , Antibacterianos/química , Metabolismo dos Carboidratos , Cloro/química , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Sequência Conservada , Farmacorresistência Bacteriana/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica , Modelos Genéticos , Dados de Sequência Molecular , Estrutura Molecular , Oxirredução , Salicilatos/química , Salicilatos/metabolismo , Alinhamento de Sequência , Streptomyces antibioticus/genética , Streptomyces antibioticus/metabolismo
18.
Onco Targets Ther ; 9: 3783-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27382314

RESUMO

BACKGROUND: The purpose of this study was to retrospectively evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous microwave ablation (MWA) combined with synchronous transcatheter arterial chemoembolization (TACE) in patients with colorectal liver metastases (CRLM). PATIENTS AND METHODS: A retrospective analysis was performed in 30 patients who were treated with ultrasound-guided percutaneous MWA combined with synchronous TACE for colorectal cancer liver metastases from November 2011 to December 2014 in Zhongshan Hospital, Fudan University. The response of the tumor to treatment was evaluated by follow-up computed tomography and/or magnetic resonance imaging. Local tumor control, procedure-related complications, and long-term survival data were analyzed. RESULTS: A total of 30 patients with 43 tumors ranging in size from 1.4 cm to 10.0 cm were analyzed. The patients' mean age was 61.6±10.3 years (range, 44.0-78.0 years). The median follow-up time was 26.5±10.4 months (range, 13.3-50.6 months). The complete ablation rate was 81.4% (35/43 lesions) for CRLM. Complete response was achieved in eight cases (26.7%), and partial response was achieved in 17 cases (56.7%) 1 month after the procedure. The objective response rate (complete response + partial response) was 83.4%. Progression-free survival and overall survival were 5.0 months and 11.0 months, respectively. The 12-month and 24-month survival rates were 46.7% and 25.4%, respectively. A total of 22 patients succumbed during follow-up due to tumor progression. No major complications or perioperative mortalities were recorded. CONCLUSION: Ultrasound-guided percutaneous MWA combined with synchronous TACE therapy is a safe and effective modality for patients with CRLM.

19.
World J Gastroenterol ; 21(7): 2229-35, 2015 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-25717263

RESUMO

Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension.


Assuntos
Fístula Arteriovenosa/complicações , Artéria Hepática/anormalidades , Hipertensão Portal/etiologia , Veia Porta/anormalidades , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/terapia , Embolização Terapêutica , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/fisiopatologia , Hipertensão Portal/terapia , Masculino , Flebografia/métodos , Pressão na Veia Porta , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Onco Targets Ther ; 8: 595-600, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25792843

RESUMO

BACKGROUND: The aim of this study was to determine the therapeutic efficacy and safety of transarterial chemoembolization (TACE) with gemcitabine and oxaliplatin in patients with advanced biliary tract cancer (BTC). METHODS: We retrospectively analyzed the outcomes for 65 patients with advanced BTC treated by TACE with gemcitabine 1,000 mg/m(2) and oxaliplatin 100 mg/m(2). Follow-up laboratory tests and computed tomography or magnetic resonance imaging were performed routinely to evaluate the response of the tumor to treatment. All patients were assessed for adverse effects. RESULTS: Of the 65 patients, 19 (29.2%) achieved a partial response, 36 (55.4%) showed stable disease, and ten (15.4%) showed progressive disease. The overall response rate was 29.2%. At the end of this study, five patients were still alive. The median overall survival was 12.0 months (95% confidence interval 8.5-15.5). There were no serious complications after TACE. CONCLUSION: The disease control rate and overall survival in this retrospective study were consistent with those in previous reports. TACE with gemcitabine and oxaliplatin was well tolerated and highly effective in patients with advanced BTC.

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