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Meng M.-B.,University of Sichuan | Meng M.-B.,Tianjin Medical University | Jiang X.-D.,Lianyungang First Peoples Hospital | Deng L.,University of Sichuan | And 9 more authors.
Radiotherapy and Oncology | Year: 2013

Purpose: This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT). Methods: Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 non-small cell lung-cancer (NSCLC) patients. Eight-week female C57BL/6J mice were randomized to receive rh-Endo or control (saline) once daily for 12 days when Lewis lung carcinoma (LLC) reached approximately 100-150 mm3. On planned days, tumors were measured for cell apoptosis, microvessel density, pericytes, blood-vessel morphology, and tumor hypoxia. The tumor response under different combinations of rh-Endo and RT schedules was evaluated. Results: Tumor hypoxia was significantly reduced 5 days after rh-Endo in NSCLC patients, and a similar result was found in the LLC mouse model. The anti-tumor effect was markedly enhanced when RT was administered within the remodeling period compared to any other treatment schedule. rh-Endo treatment remodeled the tumor vasculature after 5 days by reducing microvessel density and increasing pericytic coverage of the vessel endothelium. Conclusion: This study demonstrated decreased hypoxia in animals and patients upon rh-Endo treatment, which also enhanced the radioresponse within the vasculature-remodeling period. The optimal clinical combination of rh-Endo and RT warrants further investigation. © 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology.

Zhao J.,Sichuan Provincial Cancer Hospital | Li L.,Sichuan Provincial Cancer Hospital | Peng L.,Sichuan Provincial Cancer Hospital
International Journal of Clinical and Experimental Pathology | Year: 2015

The previous studies identify mammalian heart is terminal differentiation organs without regenerative capacity. Recently, there is some evidence point that cardiomyocytes are not terminally differentiated cells and cell proliferation may be stimulated in the pathologic heart. The aim of this study is to discover the possible mechanism which involved in cardiomyocytes proliferation process. In this study, the proliferation assay and cell cycle assay showed the proliferation of cardiomyocytes was inhibited when the cells treated with MAPK1 inhibitor. Moreover, the bioinformatics analysis revealed MAPK1 was positively correlated with MALAT1. Meanwhile, the expression of MALAT1 in H9C2 cells with the treatment of MAPK1 siRNA was obvious lower than scramble siRNA treated group. Finally further study suggested H9C2 cells treated with Wortmannin in combination with LY294002 (PI3K/AKT signaling pathway inhibitor), the expression of MALAT1 was dramatically decreased. These results indicated that MAPK1 was able to increase the proliferation of cardiomyocytes via up-regulating the expression of MALAT1 through PI3K/AKT signaling pathway.

Xue J.,University of Sichuan | Li X.,University of Sichuan | Lu Y.,University of Sichuan | Gan L.,University of Sichuan | And 8 more authors.
Molecular Therapy | Year: 2013

Radiation-induced lung injury (RILI) presents a common and major obstacle in the radiotherapy of thoracic cancers. The aim of this study was to examine whether RILI could be alleviated by mesenchymal stem cells (MSCs) expressing soluble transforming growth factor-β (TGF-β) type II receptor via an adenovirus (Ad-sTβR). Here, we systemically administered male MSCs into female mice challenged with thoracic irradiation. The data showed that either MSCs or Ad-sTβR transduced MSCs (Ad-sTβR-MSCs) specifically migrated into radiation-injured lung. Ad-sTβR-MSCs obviously alleviated lung injury, as reflected by survival and histopathology data, as well as the assays of malondialdehyde (MDA), hydroxyproline, plasma cytokines, and the expression of connective tissue growth factor (CTGF) and a-smooth muscle actin (a-SMA). Furthermore, MSCs and Ad-sTβR-MSCs could adopt the characteristics of alveolar type II (ATII) cells. However, the MSCs levels in the lungs were relatively low to account for the noted therapeutic effects, suggesting the presence of other mechanisms. In vivo, MSCs-conditioned medium (MSCs CM) significantly attenuated RILI. In vitro, MSCs CM protected ATII cells against radiation-induced apoptosis and DNA damage, and modulated the inflammatory response, indicating the beneficial effects of MSCs are largely due to its paracrine activity. Our results provide a novel insight for RILI therapy that currently lack efficient treatments. © The American Society of Gene &Cell Therapy.

Zhao J.,Sichuan Provincial Cancer Hospital | Li L.,Sichuan Provincial Cancer Hospital | Peng L.,Sichuan Provincial Cancer Hospital
International Journal of Clinical and Experimental Medicine | Year: 2015

The aim of this study was to investigate the clinical outcome of intracardiac echocardiography (ICE) for transcatheter closure of atrial septal defect (ASD) compared with the trans-esophageal echocardiography (TEE) guided method. From May 2010 to April 2011, 46 patients who underwent ICE guided (n = 23) or TEE guided (n = 23) transcatheter closure of ASD were analyzed retrospectively. We compared the demographic characteristic, procedure parameters and outcomes between ICE-and TEE-guided groups. No significant difference was found between 2 groups on demographic characteristics. Fluoroscopy time and procedure time was significantly decreased in ICE guided group than that in TEE-guided group. In addition, no significant difference was found on treatment outcomes, complications between these 2 groups. ICE-guided ASD occlusion is safe and effective method, which provides more accurate anatomical information, shorter fluoroscopy time and procedure time. © 2015, E-Century Publishing Corporation. All rights reserved.

Zhao Y.,Sichuan Provincial Cancer Hospital | Qi G.,Sichuan Provincial Cancer Hospital | Yin G.,Sichuan Provincial Cancer Hospital | Wang X.,Sichuan Provincial Cancer Hospital | And 5 more authors.
Radiation Oncology | Year: 2014

Background: The accuracy of dose calculation is crucial to the quality of treatment planning and, consequently, to the dose delivered to patients undergoing radiation therapy. Current general calculation algorithms such as Pencil Beam Convolution (PBC) and Collapsed Cone Convolution (CCC) have shortcomings in regard to severe inhomogeneities, particularly in those regions where charged particle equilibrium does not hold. The aim of this study was to evaluate the accuracy of the PBC and CCC algorithms in lung cancer radiotherapy using Monte Carlo (MC) technology. Methods and materials: Four treatment plans were designed using Oncentra Masterplan TPS for each patient. Two intensity-modulated radiation therapy (IMRT) plans were developed using the PBC and CCC algorithms, and two three-dimensional conformal therapy (3DCRT) plans were developed using the PBC and CCC algorithms. The DICOM-RT files of the treatment plans were exported to the Monte Carlo system to recalculate. The dose distributions of GTV, PTV and ipsilateral lung calculated by the TPS and MC were compared. Result: For 3DCRT and IMRT plans, the mean dose differences for GTV between the CCC and MC increased with decreasing of the GTV volume. For IMRT, the mean dose differences were found to be higher than that of 3DCRT. The CCC algorithm overestimated the GTV mean dose by approximately 3% for IMRT. For 3DCRT plans, when the volume of the GTV was greater than 100 cm3, the mean doses calculated by CCC and MC almost have no difference. PBC shows large deviations from the MC algorithm. For the dose to the ipsilateral lung, the CCC algorithm overestimated the dose to the entire lung, and the PBC algorithm overestimated V20 but underestimated V5; the difference in V10 was not statistically significant. Conclusions: PBC substantially overestimates the dose to the tumour, but the CCC is similar to the MC simulation. It is recommended that the treatment plans for lung cancer be developed using an advanced dose calculation algorithm other than PBC. MC can accurately calculate the dose distribution in lung cancer and can provide a notably effective tool for benchmarking the performance of other dose calculation algorithms within patients. © Zhao et al.; licensee BioMed Central.

Tao P.,Sichuan Provincial Cancer Hospital
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2012

To assess the association of smoked meat intake, SULT1A1 polymorphism as well as their combined effects with breast cancer risk. A total of 400 newly diagnosed breast cancer cases from a cancer hospital in Sichuan province and 400 healthy controls from participants of physical examination in a hospital in Chengdu city were recruited from May 2007 to July 2009. A valid questionnaire was designed to collect their demographic characteristics and breast cancer risk factors. Daily intake of foods was collected using semi-quantitative frequency questionnaire and then the daily intake of smoked meat was calculated and transformed to energy-adjusted smoked meat intake by the residual method. Gene sequencing was used to analyze SULT1A1 Arg213His genotypes. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs). The energy-adjusted daily intake of smoked meat (Median (P25, P75)) was 8.65 (3.63, 18.44) g/d in cases and 4.44 (0.19, 8.71) g/d in controls. The frequency of SULT1A1 variant allele was 14.75% (59/400) among cases and 12.75% (51/400) among controls. High energy-adjusted daily intake of smoked meat (≥ 4.44 g/d) was significantly associated with breast cancer risk among premenopausal (OR = 2.31, 95%CI: 1.46 - 3.66) and postmenopausal subjects (OR = 3.13, 95%CI: 1.89 - 5.17). High energy-adjusted daily intake of smoked meat combined with carrying SULT1A1 variant allele elevated breast cancer risk among premenopausal (OR = 3.31, 95%CI: 1.66 - 6.62) and postmenopausal subjects (OR = 3.81, 95%CI: 1.79 - 8.10). High smoked meat intake contributes to high risk of breast cancer. SULT1A1 variant allele increases breast cancer risk among subjects who were exposed to high smoked meat intake.

Xu G.-H.,Sichuan Provincial Cancer Hospital
Chinese Journal of Radiology | Year: 2010

Objective: To explore the long-term effect of bronchial artery embolization(BAE) in patients with massive hemoptysis and the factors associated with prognosis. Methods: Ninety six patients underwent BAE from 2002 to 2008 for the management of mass hemoptysis were retrospectively analyzed. Of them, BAE was successfully performed in 94 patients (mean age 43 years, age range 21 to 80 years), including active or inactive tuberculosis (89 cases), bronchiectasis (2 cases) and pulmonary carcinoma (5 cases). Results: BAE resulted in an immediate cessation of hemoptysis in 94 of the initial 96 patients (97.9%). The rate of hemoptysis controlling at 30 d, 90 d, 1 year and 2 year after the BAE was 93.6% (88/94), 86.2% (81/94), 81.9% (77/94) and 78.7% (74/94) respectively. Haemoptysis recurred in 9 patients in 30 days after the BAE due to missing of target vessel or recanalization. Five patients had recurrence of haemoptysis after 30 days and 2 patients recurrent after 90 days due to development of systemic collateral, progress in primary lesions and secondary infection. Conclusion: BAE is an effective technique in the emergency treatment of massive hemoptysis. Avoiding missing target vessel, selecting the appropriate embolic material, paying attention to treatment of the primary disease after BAE, and preventing infection would improve the effects of BAE for massive hemoptysis.

PubMed | Sichuan Provincial Cancer Hospital
Type: Journal Article | Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2016

To analyze the characteristics and factors affecting the recurrence in esophageal cancer within the first year after esophagectomy.We reviewed retrospectively the clinical and follow-up data of 320 patients who underwent surgical treatment from April 2009 to April 2013 in Sichuan Provincial Cancer Hospital.72 cases (72/320, 22.5%) had tumor recurrence within the first year after surgery. The average recurrence time was 6.893.53 months and the median recurrence time was 6.02 months. Univariate analysis showed that T stage, N stage, G grade, and pathological stage are related to the recurrence (P<0.05 for all). Logistic regression analysis showed that pathological stage is an independent risk factor for recurrence (P=0.002). There were 46 cases (46/72, 63.9%) of local recurrence and 26 cases (26/72, 36.1%) of distant metastasis. Among the 46 cases of local recurrence, 27 cases (27/46, 58.7%) had upper mediastinal lymph node metastasis. Among the 26 cases of distant metastasis, there were 11 cases (11/26, 42.3%) of pulmonary metastasis. Among the 72 cases of recurrence, the average number of dissected lymph nodes and involved nodes were 29.4011.41 and 4.375.65, respectively, in patients with distant metastasis, and 21.1810.37 and 1.912.14, respectively, in patients with local recurrence. Both the number of dissected and involved lymph nodes were significantly higher in the patients with distant metastasis (P<0.05).Lymph node metastasis is the most common pattern of recent relapse after esophagectomy, and pathological stage is an independent risk factor for recurrence within the first year after surgery. Standardized lymph node dissection and rational treatment strategy is the key measures to reduce early recurrence of esophageal cancer.

PubMed | Sichuan Provincial Cancer Hospital and Fox Chase Cancer Center
Type: Journal Article | Journal: Medical physics | Year: 2016

Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT.Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H&N, breast, lung, pancreas and prostate patients and compared.All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT.IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

PubMed | Sichuan Provincial Cancer Hospital
Type: Journal Article | Journal: Oncology reports | Year: 2016

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortalities in China. Although advances have been made in treatments, the prognosis of HCC patients has not improved significantly. MicroRNAs (miRNA) play important roles in all stage of the progress of HCC. miR-4782-3p takes part in the pathogenesis of non-small cell lung cancer (NSCLC). However, the role of miR-4782-3p in HCC remains unknown. In the present study, we found that miR-4782-3p had low expression in HCC tissues. The low expression of miR-4782-3p indicated shorter survival of HCC patients. Moreover, the low expression of miR-4782-3p promoted HCC cells growth and inhibited cell apoptosis. We confirmed that USP14 was targeted by miR-4782-3p in HCC cells.

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