Shandong Cancer Hospital and Institute

Jinan, China

Shandong Cancer Hospital and Institute

Jinan, China
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Wang X.-B.,Jining Medical University | Zhou H.-Y.,Shandong Cancer Hospital and Institute
Biomedicine and Pharmacotherapy | Year: 2015

Molecularly targeted therapy emerged as a novel therapeutic strategy in the treatment of multiple cancers. In the present study, we have developed gemcitabine (GEM)-loaded cetuximab (CET) surface modified poly(lactic) acid (PLA) nanoparticles (NP) (CET-GEM/PLA NP) to target to epidermal growth factor receptor (EGFR) overexpressing non-small cell lung cancer (A549) cells. The resultant CET-GEM/PLA NP showed a very uniform particle size of. ~. 120. nm and spherical morphology. It exhibited a pH-dependent controlled release pattern. A sustained release of drug in the physiological conditions and faster release in tumor pH will greatly improve the chemotherapeutic efficiency of therapeutic system. Higher or enhanced cellular uptake of CET-GEM/PLA NP in A549 cancer cells clearly indicates the EGFR-mediated receptor based active targeting. Nearly, a two-fold increase in fluorescent intensity was observed for CET-GEM/PLA NP comparing to that of non-targeted NP in the cancer cells. EGFR-mediated internalization of the targeted NP was further confirmed by the confocal microscopy. MTT assay clearly showed the enhanced cell killing effect of CET-conjugated NP due to the selective delivery of GEM to the EGFR over expressing cancer cells. Finally, comparing to the non-targeted NP, CET-GEM/PLA NP showed greater level of cell apoptosis (early and late apoptosis. ~. 40%). Our results showed that antibody conjugation on the surface of NP could be a potential treatment strategy for EGFR over expressing cancer cells. This suggests that CET-GEM/PLA NP could be potentially used for the treatment of NSCLC (lung cancers). © 2015 Published by Elsevier Masson SAS.


Zhang K.,Shandong Academy of Sciences | Song L.,Shandong Cancer Hospital and Institute
PLoS ONE | Year: 2014

Background: The associations between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial. Methodology/Principal Findings: An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between Fok1, poly-A repeat, Bsm1, Taq1 or Apa1 polymorphisms of the VDR gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI) were estimated based on a fixed-effect model (FEM) or random-effect model (REM), depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the Fok1 polymorphism of the VDR gene was associated with an increased risk of breast cancer (ff vs. Ff+FF, OR: 1.09, 95%CI: 1.02 to 1.16, p = 0.007). No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies. Conclusion: A meta-analysis of high-quality studies demonstrated that the Fok1 polymorphism of the VDR gene was closely associated with breast cancer risk. © 2014 Zhang, Song.


Meng X.,Shandong Cancer Hospital and Institute | Kong F.M.S.,University of Michigan | Yu J.,Shandong Cancer Hospital and Institute
Lung Cancer | Year: 2012

Tumor hypoxia has been found to be a characteristic feature in lung cancer. It has been shown to decrease the therapeutic efficacy of radiotherapy and some forms of chemotherapy. New methods for qualitative and quantitative assessment of tumor oxygenation have made it possible to establish the prognostic significance of tumor hypoxia. The ability to determine the degree and extent of hypoxia in lung cancer is not only important prognostically, but also in the selection of patients for hypoxia-modifying treatments. To provide the best attainable quality of life for individual patients it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatment strategies. Although some markers and combinations have shown potential benefit and are associated with treatment outcome, their clinical usefulness needs to be validated in prospective trials. A review of published studies was carried out, focusing on the assessment of tumor hypoxia and the possibilities to overcome hypoxia during treatment in lung cancer. © 2011 Elsevier Ireland Ltd.


Meng X.,Shandong Cancer Hospital and Institute | Wang R.,Shandong Cancer Hospital and Institute
Journal of Cancer Research and Therapeutics | Year: 2013

Inflammatory myofibroblastic tumor (IMT) is a rare disease. We report a rare case of inflammatory myofibroblastic tumor occurs in the mediastinum. Chest contrast-enhanced computed tomography (CT) showed a heterogeneously enhanced irregular mass in the anterior mediastinum; a small pericardial effusion was also noted. The diagnosis was confirmed by histopathology and immunohistochemical study.


Yu Q.,Shandong Cancer Hospital and Institute | Yuan S.,Shandong Cancer Hospital and Institute
International Journal of Clinical and Experimental Medicine | Year: 2014

Primary malignant melanoma of the esophagus (PMME) is a rare disease, comprising 0.1-0.2% of all malignant esophageal neoplasms. The most common symptoms include progressive dysphagia, chest and back pain, choking feeling and weight loss. PMME cannot be definitely diagnosed from clinical symptoms or CT examination, but can be confirmed by histological examination or a pathological examination. Immunohistochemical examination with positive results of S-100 protein and human melanoma black 45 (HMB45) makes a definitive diagnosis. Esophagectomy is the standard treatment for localized PMME. But the prognosis is poor. Inoperableness, metastases and insensitiveness of radiotherapy and chemotherapy in advanced tumors have led to poor prognosis. Here, we report a case of a 61-year-old male with progressive dysphagia for 1 month. After barium X-ray test, chest and abdomen computed tomography examination, upper gastrointestinal endoscopy and biopsy, the patient accepted esophagectomy, then the pathologic and immunohistochemical examination conformed the diagnosis of PMME. © 2014 E-Century Publishing Corporation. All rights reserved.


Wang Y.,Shandong University | Zhang P.,Shandong University | Liu Z.,The Fifth Peoples Hospital | Wang Q.,Shandong University | And 4 more authors.
Molecular Cancer | Year: 2014

Background: CUL4A has been proposed as oncogene in several types of human cancer, but its clinical significance and functional role in human non-small cell lung cancer (NSCLC) remain unclear. Methods: Expression level of CUL4A was examined by RT-PCR and Western blot. Forced expression of CUL4A was mediated by retroviruses, and CUL4A silencing by shRNAs expressing lentiviruses. Growth capacity of lung cancer cells was measured by MTT in vitro and tumorigenesis in vivo, respectively. Results: We found that CUL4A was highly expressed in human lung cancer tissues and lung cancer cell lines, and this elevated expression positively correlated with disease progression and prognosis. Overexpression of CUL4A in human lung cancer cell lines increased cell proliferation, inhibited apoptosis, and subsequently conferred resistance to chemotherapy. On other hand, silencing CUL4A expression in NSCLC cells reduced proliferation, promoted apoptosis and resulted in tumor growth inhibition in cancer xenograft model. Mechanistically, we revealed CUL4A regulated EGFR transcriptional expression and activation, and subsequently activated AKT. Targeted inhibition of EGFR activity blocked these CUL4A induced oncogenic activities. Conclusions: Our results highlight the significance of CUL4A in NSCLC and suggest that CUL4A could be a promising therapy target and a potential biomarker for prognosis and EGFR target therapy in NSCLC patients. © 2014 Wang et al.; licensee BioMed Central Ltd.


Shi H.,Shandong Cancer Hospital and Institute | Sun M.,Shandong University | Liu L.,Shandong Cancer Hospital and Institute | Wang Z.,Shandong Cancer Hospital and Institute
Molecular Cancer | Year: 2014

Chimeric antigen receptors (CARs) are recombinant receptors that combine the specificity of an antigen-specific antibody with the T-cell's activating functions. Initial clinical trials of genetically engineered CAR T cells have significantly raised the profile of T cell therapy, and great efforts have been made to improve this approach. In this review, we provide a structural overview of the development of CAR technology and highlight areas that require further refinement. We also discuss critical issues related to CAR therapy, including the optimization of CAR T cells, the route of administration, CAR toxicity and the blocking of inhibitory molecules. © 2014 Shi et al.; licensee BioMed Central Ltd.


Meng X.,Shandong Cancer Hospital and Institute | Huang Z.,Shandong University | Teng F.,Shandong Cancer Hospital and Institute | Xing L.,Shandong Cancer Hospital and Institute | Yu J.,Shandong Cancer Hospital and Institute
Cancer Treatment Reviews | Year: 2015

Checkpoint blockades turn on a new paradigm shift in immunotherapy for cancer. Remarkable clinical efficacy, durable response and low toxicity of programmed death 1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockades have been observed in various malignancies. However, a lot of cancer patients failed to respond to the PD-1/PD-L1 checkpoint blockades. It is crucial to identify a biomarker to predict the response to checkpoint blockades. The overexpression of PD-L1 is an important and widely-explored predictive biomarker for the response to PD-1/PD-L1 antibodies. However PD-L1 staining cannot be used to accurately select patients for PD-1/PD-L1 pathway blockade due to the low prediction accuracy and dynamic changes. Tumor-infiltrating immune cells and molecules in the tumor microenvironment, or along with PD-L1 expression, may be important in predicting clinical benefits of PD-1/PD-L1 checkpoint blockades. Gene analysis has proven to be new approach for judging the potential clinical benefit of immune checkpoint inhibitors, such as mutational landscape and mismatch-repair deficiency. Further preclinical and clinical studies are necessary to carry out before its application in clinical practice. Challenges should be overcome to identify patients accurately who will benefit from PD-1/PD-L1 checkpoint blockades. In this review, we focus on the predictive biomarkers for checkpoint blockades of PD-1/PD-L1 pathway. © 2015 Elsevier Ltd.


Xu S.-H.,Shandong University | Yang Y.-L.,Shandong University | Han S.-M.,Shandong Cancer Hospital and Institute | Wu Z.-H.,Shandong University
World Journal of Surgical Oncology | Year: 2014

Background: The purpose of the present study was to examine the expression levels of microRNA-9 (miR-9) in osteosarcoma tissues and normal bone tissues, and investigate the relationships between miR-9 expression, clinicopathological features and the prognosis of patients with osteosarcoma.Methods: The expression levels of miR-9 in osteosarcoma tissues and corresponding non-cancerous tissues were detected using a real-time quantitative assay. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values.Results: Compared to non-cancerous bone tissues, the expression levels of miR-9 in osteosarcoma tissues were significantly elevated (P < 0.001). We found that the expression level of miR-9 was significantly associated with tumor size (P = 0.011), clinical stage (P = 0.009) and distant metastasis (P < 0.001). The Kaplan-Meier curve showed that patients with low miR-9 expression survived significantly longer than patients with high miR-9 expression (P = 0.0017). Multivariate analysis suggested that miR-9 expression level (P = 0.002) is an independent prognostic factors for overall survival.Conclusions: The findings of our study suggest that increased miR-9 expression has a strong correlation with the aggressive progression of osteosarcoma and its overexpression is a statistically significant risk factor affecting overall survival, suggesting that increased miR-9 expression could be a valuable marker of tumor progression and for prognosis of osteosarcoma. © 2014 Xu et al.; licensee BioMed Central Ltd.


Zhao X.,Shandong Cancer Hospital and Institute | Liu M.,Shandong Cancer Hospital and Institute | Li D.,Shandong Cancer Hospital and Institute
Molecular and cellular biochemistry | Year: 2015

Oleanolic acid (OA) is a natural compound from plants with anti-tumor activities. However, the mechanism of the inhibitory effect of OA on cell cycle progression has not been completely explored. We employed several lung carcinoma cell lines to investigate the cell cycle-related molecular pathway affected by OA. The data revealed that OA suppressed the proliferation of lung cancer cells in both dose- and time-dependent manners, along with an increase in miR-122 abundance. The suppression of miR-122 abolished the effect of OA on lung cancer cells. CCNG1 and MEF2D, two putative miR-122 targets, were found to be downregulated by OA treatment. Restoring their expression counteracted the effect of OA on lung carcinoma cells. OA was further shown to induce the expression of miR-122-regulating transcriptional factors in lung cancer cells. Collectively, OA induced cell cycle arrest in lung cancer cells through miR-122/Cyclin G1/MEF2D pathway. This finding may contribute to the understanding of the molecular mechanism of OA's anti-tumor activity.

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