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To compare the transcatheter arterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in the treatment of single branch portal vein tumor thrombus(PVTT)in patients with hepatocellular carcinoma (HCC) so as to evaluate the safety, control rate, prognostic factors and overall survival. From January 2004 to December 2007, 50 HCC patients (< 5 cm in diameter and 3 parenchymal lesions) with concurrent PVTT were enrolled and treated by TACE alone or TACE plus RFA randomly (TACE, n = 25; TACE-RFA, n = 25). In TACE group, the intra-hepatic lesions received TACE sequentially with RFA; in TACE-RFA group, PVTT and intra-hepatic lesions were treated with TACE sequentially with RFA separately. Strict follow-up was conducted by computed tomography and alpha-fetoprotein (AFP) assay. The survival time was analyzed by the Kaplan-Meier method and Cox regression analysis was performed to evaluate the prognostic factors. Of all 50 HCC patients with single branch PVTT with TACE or RFA, 47 patients (TACE, n = 24; TACE-RFA, n = 23) received all the scheduled procedures and completed the follow-up. Two patients (8.3%) in TACE group had liver dysfunction versus none in TACE-RFA group, 2 patients (8.7%) developed bile duct injury in TACE-RFA group related with the RFA procedure. The OR (overall response) for PVTT was 54.2% (complete response (CR) 8.3%, partial response (PR) 45.8%) in TACE group while 87.0% (CR 60.9%, PR 26.1%) in TACE-RFA group during the follow-up. From the definite diagnosis of HCC, the median survival was 8 months. And the 1-, 2- & 3-year survival rates were 33.3%, 12.5%, 8.3% in TACE group. And 26 months, 65.2%, 47.8%, 30.4% in TACE-RFA group respectively. The difference between two groups was significant. From the definite diagnosis of PVTT, the respective data were 7 months, 12.5% and 4.2%, 0 in TACE group versus 22 months, 52.2%, 34.8%, and 8.7% in TACE-RFA group with a significant P value. In multivariate analysis, only therapy (TACE or TACE-RFA) showed a protective value (hazard rate 0.430 vs 0.345, P < 0.05). Survival was not correlated with age, intra-hepatic tumor status, liver functions and AFP level for all patients. RFA is both safe and efficacious to prolong survival in the treatment of single branch PVTT plus TACE in selected HCC patients. It may provide rationales for further studies of evaluating the outcome of RFA plus other therapies in the treatment of HCC with single branch PVTT. Source

Li S.,Sun Yat Sen University | Liu H.,Sun Yat Sen University | Li L.,State Key Laboratory of Oncology in Southern China | Luo N.-Q.,Sun Yat Sen University | And 3 more authors.
Applied Physics Letters | Year: 2011

The water-adsorptive capabilities of Gd2 O3 @MCM-41 as contrast agents with various gadolinium additions were evaluated by molecular dynamic simulation, which indicates that increasing gadolinum leads to the decrease in water molecules adsorbed on the surfaces of mesoporous silica and Gd2 O3 nanocluster. Gd2 O3 @MCM-41 nanoparticles were synthesized by a one-step method. The measured microstructure and water-adsorptive capability of Gd2 O3 @MCM-41 consist with their simulated counterparts. The observation disclosed that the nanoparticles injected within mice were distributed in their liver and tumor. The enhancement of in vivo magnetic resonance imaging was detected in the tumor and inferior vena cava of the mice contrasted with Gd2 O3 @MCM-41. © 2011 American Institute of Physics. Source

Zhang L.,State Key Laboratory of Oncology in Southern China
Journal of radiation research | Year: 2012

This study aimed to identify the potential benefits and limitations of a new volumetric modulated arc therapy (VMAT) planning system in Monaco, compared with conventional intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT). Four-dimensional CT scans of 13 patients with abdominal lymph node metastasis from hepatocellular carcinoma were selected. Internal target volume was defined as the combined volume of clinical target volumes (CTVs) in the multiple 4DCT phases. Dose prescription was set to 45 Gy for the planning target volume (PTV) in daily 3.0-Gy fractions. The PTV dose coverage, organs at risk (OAR) doses, delivery parameters and treatment accuracy were assessed. Compared with 3DCRT, both VMAT and IMRT provided a systematic improvement in PTV coverage and homogeneity. Planning objectives were not fulfilled for the right kidney, in which the 3DCRT plans exceeded the dose constraints in two patients. Equivalent target coverage and sparing of OARs were achieved with VMAT compared with IMRT. The number of MU/fraction was 462 ± 68 (3DCRT), 564 ± 105 (IMRT) and 601 ± 134 (VMAT), respectively. Effective treatment times were as follows: 1.8 ± 0.2 min (3DCRT), 6.1 ± 1.5 min (IMRT) and 4.8 ± 1.0 min (VMAT). This study suggests that the VMAT plans generated in Monaco improved delivery efficiency for equivalent dosimetric quality to IMRT, and were superior to 3DCRT in target coverage and sparing of most OARs. However, the superiority of VMAT over IMRT in delivery efficiency is limited. Source

Lv P.,Chinese Academy of Sciences | Lv P.,Capital Medical University | Wang Y.,China National Institute of Standardization | Ma J.,Chinese Academy of Sciences | And 7 more authors.
Oncotarget | Year: 2014

Nasopharyngeal carcinoma (NPC), while uncommon worldwide, is a major health problem in China. Although local radiation and surgery provide good control of NPC, better treatments that permit reductions in radiation dosing are needed. Inhibition of protein phosphatase 2A (PP2A), a ubiquitous multifunctional enzyme with critical roles in cell cycle regulation and DNA-damage response, reportedly sensitizes cancer cells to radiation and chemotherapy. We studied PP2A inhibition with LB100, a small molecule currently in a Phase I clinical trial, on radiosensitization of two human nasopharyngeal cell lines: CNE1, which is reportedly radioresistant, and CNE2. In both cell lines, LB100 exposure increased intracellular p-Plk1, TCTP, and Cdk1 and decreased p53, changes associated with cell cycle arrest, mitotic catastrophe and radio-inhibition of cell proliferation. Mice bearing subcutaneous xenografts of either cell line were administered 1.5 mg/kg LB100 daily for three days and a single dose of 20 Gy radiation (day 3), which produced marked and prolonged tumor mass regression (dose enhancement factors of 2.98 and 2.27 for CNE1 and CNE2 xenografts, respectively). Treatment with either LB100 or radiation alone only transiently inhibited xenograft growth. Our results support further exploration of PP2A inhibition as part of radiotherapy regimens for NPC and potentially other solid tumors. Source

Lian Q.,University of Hong Kong | Zhang Y.,University of Hong Kong | Zhang J.,Singapore Institute of Medical Biology | Zhang H.K.,Central Laboratory of Shenzhen Maternity | And 10 more authors.
Circulation | Year: 2010

Background: Aging and aging-related disorders impair the survival and differentiation potential of bone marrow mesenchymal stem cells (MSCs) and limit their therapeutic efficacy. Induced pluripotent stem cells (iPSCs) may provide an alternative source of functional MSCs for tissue repair. This study aimed to generate and characterize human iPSC-derived MSCs and to investigate their biological function for the treatment of limb ischemia. Methods and results: Human iPSCs were induced to MSC differentiation with a clinically compliant protocol. Three monoclonal, karyotypically stable, and functional MSC-like cultures were successfully isolated using a combination of CD24 and CD105 sorting. They did not express pluripotent-associated markers but displayed MSC surface antigens and differentiated into adipocytes, osteocytes, and chondrocytes. Transplanting iPSC-MSCs into mice significantly attenuated severe hind-limb ischemia and promoted vascular and muscle regeneration. The benefits of iPSC-MSCs on limb ischemia were superior to those of adult bone marrow MSCs. The greater potential of iPSC-MSCs may be attributable to their superior survival and engraftment after transplantation to induce vascular and muscle regeneration via direct de novo differentiation and paracrine mechanisms. Clusions: Functional MSCs can be clonally generated, beginning at a single-cell level, from human iPSCs. Patient-specific iPSC-MSCs can be prepared as an "off-the-shelf" format for the treatment of tissue ischemia. Copyright © 2010 American Heart Association. All rights reserved. Source

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