Shandong Tumor Hospital and Institute

Jinan, China

Shandong Tumor Hospital and Institute

Jinan, China
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Wang F.,Shandong University | Li L.,Shandong University | Liu B.,Shandong Tumor Hospital and Institute | Chen Z.,Shandong Tumor Hospital and Institute | Li C.,Shandong University
Biomedicine and Pharmacotherapy | Year: 2017

This work aimed to develop hyaluronic acid (HA) decorated pluronic 85 (P85) coated solid lipid nanoparticles (SLN) loaded with paclitaxel (HA-PTX-P85-SLN) and to evaluate its potential to overcome drug resistance and to increase antitumor efficacy in mice bearing cervical and breast tumor. P85-Distearoyl Phosphoethanolamine (DSPE) was synthesized from P85 and DSPE by coupling in the presence of 1,10-carbonyldiimidazole (CDI) as a catalyst. The SLN were prepared by the hot homogenization technique and electrostatic interaction. PTX-loaded SLN was characterized for mean diameter, zeta potential, morphology, entrapment efficiency (EE), drug loading capacity (LC) and in vitro drug release. In vivo animal evaluation containing antitumor effect, pharmacokinetics and biodistribution were conducted in mice bearing cervical and breast tumor. The HA-PTX-P85-SLN showed a mean diameter of 160.3 nm, negative zeta potential (−31.6 mV), EE of 88.2%, and LC of 4.9%. PTX from HA-PTX-P85-SLN exhibited greater sustained drug release profiles compared free PTX. Pharmacokinetics results indicated that HA-PTX-P85-SLN exhibited a 5.5-fold increase in AUC in comparison to free PTX. Biodistribution results revealed that HA-PTX-P85-SLN exhibited higher tumor drug concentration compared with free PTX. © 2016 Elsevier Masson SAS

Li L.,Fudan University | Hu M.,Shandong Tumor Hospital and Institute | Zhu H.,Peking Union Medical College | Zhao W.,Shandong Tumor Hospital and Institute | And 2 more authors.
Clinical Lung Cancer | Year: 2010

Introduction: The aim of this study was to compare glucose metabolism and hypoxia using 18F- fluorodeoxyglucose (18F-FDG) and 18F-fluoroerythronitroimidazole (18F-FETNIM) positron emission tomography (PET) and investigate their prognostic role on survival in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-six patients with NSCLC were imaged with 18F-FETNIM PET/computed tomography (CT), and 11 cases also with 18F-FDG PET/CT imaging among those with significant 18F-FETNIM uptake, a few days before any chemo/adiation therapy. The maximum standardized uptake value (SUVmax) was used to depict 18F-FDG uptake, and hypoxic volume (HV) and tumor:blood ratio (T/Bmax) were used to quantify hypoxia. Overall survival (OS) after treatment was selected as the endpoint of the study. Results: Twenty-two patients (84.6%) had significant 18F-FETNIM uptake in the primary tumor. The correlations between the overall tumor SUVmax of 18F-FDG and HV, T/Bmax ratio of 18F-FENTIM in 11 patients were small and without significant difference. In univariate analyses, log-rank tests were used to compare Kaplan-Meier survival curves. 18F-FETNIM T/Bmax ratio and HV were strong predictors for OS, and 18F-FDG uptake of the primary lesions did not have a significant relationship with survival. In multivariate survival analysis, only 18F-FETNIM T/Bmax ratio was found to be an independent prognostic factor. Conclusion: Imaging using both 18F-FETNIM and 18F-FDG appears to be beneficial in the evaluation of solid tumors. 18F-FETNIM imaging provides us with a valuable method to detect tumor hypoxia and predict OS. These preliminary results warrant validation in larger trials.

Jin S.,Shandong University | Li D.,Shandong Normal University | Wang H.,Shandong University | Yin Y.,Shandong University | Yin Y.,Shandong Tumor Hospital and Institute
Journal of Applied Clinical Medical Physics | Year: 2013

Accurate registration of 18F-FDG PET (positron emission tomography) and CT (computed tomography) images has important clinical significance in radiation oncology. PET and CT images are acquired from 18F-FDG PET/CT scanner, but the two acquisition processes are separate and take a long time. As a result, there are position errors in global and deformable errors in local caused by respiratory movement or organ peristalsis. The purpose of this work was to implement and validate a deformable CT to PET image registration method in esophageal cancer to eventually facilitate accurate positioning the tumor target on CT, and improve the accuracy of radiation therapy. Global registration was firstly utilized to preprocess position errors between PET and CT images, achieving the purpose of aligning these two images on the whole. Demons algorithm, based on optical flow field, has the features of fast process speed and high accuracy, and the gradient of mutual information-based demons (GMI demons) algorithm adds an additional external force based on the gradient of mutual information (GMI) between two images, which is suitable for multimodality images registration. In this paper, GMI demons algorithm was used to achieve local deformable registration of PET and CT images, which can effectively reduce errors between internal organs. In addition, to speed up the registration process, maintain its robustness, and avoid the local extremum, multiresolution image pyramid structure was used before deformable registration. By quantitatively and qualitatively analyzing cases with esophageal cancer, the registration scheme proposed in this paper can improve registration accuracy and speed, which is helpful for precisely positioning tumor target and developing the radiation treatment planning in clinical radiation therapy application.

Wang L.,Shandong University | Cheng H.,Shandong University | Liu Y.,Shandong University | Yu W.,Shandong University | And 4 more authors.
Annals of Surgical Oncology | Year: 2011

Background: β-catenin plays an important role in colorectal tumorigenesis. Relatively little is known about the relationship between β-catenin overexpression and liver metastasis. The purpose of this study was to investigate whether nuclear β-catenin overexpression in colorectal cancer is associated with synchronous liver metastasis. Methods: The β-catenin expression in tumor tissue from 486 patients with colorectal cancer was examined by immunohistochemistry. The relationship between nuclear β-catenin expression in colorectal cancers and liver metastatic lesions and other clinicopathological characteristics was analyzed. Univariate analysis and logistic multivariate regression analysis were adopted to discriminate risk factors of liver metastasis. Results: Nuclear β-catenin overexpression at the invasive front of the primary tumor in patients with liver metastasis is more evident than that in patients without liver metastasis (71.5% vs. 29.3%; P < 0.001). Nuclear β-catenin expression in primary tumors had a positive correlation with that in the matched metastatic lesions (r = 0.499, P < 0.001). Univariate and multivariate analyses indicated that overexpression of nuclear β-catenin at the invasive front in colorectal cancer correlated with liver metastasis. Conclusions: Overexpression of nuclear β-catenin at the invasive front in colorectal cancer is strongly associated with liver metastasis and may be a promising predictor of liver metastasis. © 2011 Society of Surgical Oncology.

Liu B.,Shandong Tumor Hospital and Institute | Han S.-M.,Shandong Tumor Hospital and Institute | Tang X.-Y.,Shandong Tumor Hospital and Institute | Han L.I.,Shandong Tumor Hospital and Institute | Li C.-Z.,Shandong University
Oncology Reports | Year: 2014

Ovarian cancer is a highly invasive and metastatic disease with poor prognosis, particularly if this disease is diagnosed at an advanced stage, which is often the case. Researchers have argued that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties; however, the relevant molecular mechanisms in this setting are poorly understood. In cancer cases, the transcription factor forkhead box protein C2 (FOXC2) has been detected, but the function of this factor in ovarian cancer tumorigenesis remains unclear. In the present study, FOXC2 was overexpressed in invasive ovarian cancer cell lines and tissues. The invasive potential of ovarian cancer cells was significantly increased by ectopic FOXC2 expression but it was significantly decreased by RNA interference targeting FOXC2. E-cadherin and vimentin expression levels were modulated by FOXC2. These results indicated that FOXC2 was required for the maintenance of the mesenchymal phenotype after TGF-β1 induced EMT in human ovarian cancer cells. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies. These therapies can then be performed to treat invasive ovarian tumor.

Liu B.,Shandong Tumor Hospital and Institute | Han S.-M.,Shandong Tumor Hospital and Institute | Tang X.-Y.,Shandong Tumor Hospital and Institute | Han L.,Shandong Tumor Hospital and Institute | Li C.-Z.,Shandong University
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/ DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

To compare dosimetry, efficacy, and toxicity of intensity-modulated radiation therapy (IMRT) with para-aortic field radiotherapy in patients with para-aortic lymph node (PALN) metastasis of cervical cancer. This prospective study examined 60 patients with cervical cancer with PALN metastasis who underwent whole-pelvis radiotherapy followed by brachytherapy between November 1, 2004 and May 31, 2008. After 3 cycles of chemotherapy, patients were serially allocated into two groups and treated with IMRT or para-aortic field RT at doses of 58-68 Gy and 45-50 Gy, respectively. Treatment response was evaluated and toxicities were assessed. Patients in the IMRT group were treated with both para-aortic field RT and IMRT in order to compare the exposure dose of organs at risk. In the IMRT group, the mean dose delivered to the planning target volume was 67.5 Gy. At least 99% of the gross tumor volume received effective coverage and radical dose (median, 63.5 Gy; range, 54.5-66) during treatment. IMRT plans yielded better dose conformity to the target and better sparing of the spinal cord and small intestine than para-aortic field RT. The IMRT patients experienced less acute and chronic toxicities. The IMRT group also had higher 2- and 3-year survival rates than the para-aortic RT group (2-year, 58.8% vs 25.0%, P = 0.019; 3-year, 36.4% vs 15.6%, P = 0.016). However, no significant difference was found in 1-year survival (67.7% vs 51.3%, P =0.201). The median survival in the IMRT group was 25 months (range, 3 to 37 months). The actuarial overall survival, disease-free survival, and locoregional control rates at 2 years were 67%, 77%, and 88%, respectively, in the IMRT group. IMRT provides better clinical outcomes than para-aortic field radiotherapy in patients with PALN metastasis. However, cervical local and distal recurrence remain a problem. Long-term follow-up and studies involving more patients are needed to confirm our results.

Cao X.J.,Shandong Tumor Hospital and Institute | Hao J.F.,Shandong Tumor Hospital and Institute | Yang X.H.,Shandong Tumor Hospital and Institute | Xie P.,Shandong Tumor Hospital and Institute | And 3 more authors.
Medical Oncology | Year: 2012

The purpose of this study was to evaluate the prognostic value of expression of EGFR and nm23 in patients with advanced-stage nasopharyngeal carcinoma (NPC). The study population comprised 127 patients with stage III-IVa NPC with sufficient pretreatment tumor biopsy specimens from 2003 to 2004 and clinical follow-up data. The expression of EGFR and nm23 was detected by immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The correlation between pretreatment expression of EGFR and nm23, and the effectiveness of chemoradiotherapy was analyzed. The EGFR expression was correlated with primary lesion stage and clinical stage (P = 0.001, 0.002, respectively). There was a statistically significant association between nm23 expression and local lymph node stage (P = 0.000). The positive EGFR expression had a higher recurrent rate than the negative (P = 0.015). The positive nm23 expression had a lower distant metastasis rate than the negative (P = 0.021). Negative expression of EGFR had a significantly better 5-year OS and DFS than positive expression (P = 0.015, 0.013, respectively). Positive expression of nm23 had a significantly higher 5-year OS and DFS than negative expression (P = 0.001, 0.006, respectively). Multivariate analysis indicated that both pretreatment EGFR and nm23 expression were strong independent factors for the overall survival of patients with NPC (P = 0.000, 0.000, respectively). Our data suggested that EGFR and nm23 can serve as reliable biomarkers for prognosis prediction in patients with NPC who may benefit from alternate treatment strategy and targeted treatment. © 2011 Springer Science+Business Media, LLC.

Xie P.,Shandong Tumor Hospital and Institute | Li M.,Shandong Tumor Hospital and Institute | Zhao H.,Shandong Tumor Hospital and Institute | Sun X.,Shandong Tumor Hospital and Institute | And 2 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011

Purpose: The purpose of this meta-analysis was to evaluate the prognostic value of standard uptake value (SUV) from serial Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with head and neck cancer. Methods: We searched for articles limited to head and neck cancer, dealt with the impact of SUV on survival and published in English. The endpoints were disease-free survival (DFS), overall survival (OS), and local control (LC). Two reviewers extracted data independently. Results: Thirty-five studies were identified; of which, 26 studies involving 1,415 patients met the inclusion criteria. Pooled survival data suggested better DFS, OS, and LC in patients with low SUV of pre-treatment, and the odds ratio (OR) was 0.23, 0.24, and 0.27, respectively. Patients having tumors with low SUV of post-treatment also had significantly better DFS (OR = 0.17) and OS (OR = 0.28) than those with high SUV. Conclusions: The present meta-analysis showed that 18F-FDG uptake, as measured by the SUV before treatment and metabolic response after treatment, are valuable for predicting long-term survival in head and neck cancer. High 18F-FDG uptake may be useful for identifying patients requiring more aggressive treatment. © 2011 Springer-Verlag.

Xie P.,Shandong Tumor Hospital and Institute | Yue J.-B.,Shandong Tumor Hospital and Institute | Zhao H.-X.,Shandong Tumor Hospital and Institute | Sun X.-D.,Shandong Tumor Hospital and Institute | And 3 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2010

Purpose The purpose of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) and metabolic index (MI) from fluorine-18- fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) in patients with nasopharyngeal carcinoma (NPC). Methods From October 2002 to July 2004, 41 patients with NPC who underwent 18F-FDG PET-CT scan before and after radiotherapy were reviewed retrospectively. All patients received intensity-modulated radiotherapy using 6MV X-rays. We examined the association of MTV and the results of long-term follow-up of the patients. Results Patients having tumors with an MTV below 30 cm3 had significantly better 5-year overall survival (OS) (84.6:46.7%, P = 0.006) and disease-free survival (DFS) (73.1:40.0%, P = 0.014) than patients with an MTV of 30 cm3 or greater. And the patients with MI below 130 had significantly higher 5-year OS (88.0:43.8%, P = 0.002) and DFS (76.0:37.5%, P = 0.005) than other patients. In the Cox multivariate analysis, MI and metabolic response (MR) were predictive of DFS, and we did not find a significant relationship between standard uptake value (SUV) and OS or DFS. Conclusions The present study shows that tumor volume parameters, especially the combination of MTV and SUV in the "metabolic index", are valuable for predicting long-term survival. High MI may be useful for identifying patients requiring more aggressive treatment. © Springer-Verlag 2009.

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