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Wei J.-W.,Tianjin Medical University | Cui J.-Q.,Tianjin Medical University | Zhou X.,Tianjin Cancer Institute and Hospital | Fang C.,Hebei University | And 5 more authors.
Cancer Letters | Year: 2016

Extensive heterogeneity is a defining hallmark of glioblastoma multiforme (GBM) at the cellular and molecular levels. EGFRvIII, the most common EGFR mutant, is expressed in 24–67% of cases and strongly indicates a poor survival prognosis. By co-expressing EGFRvIII and EGFRwt, we established an EGFRvIII/wt heterogenic model. Using this approach, we confirmed that a mixture of EGFRvIII and EGFRwt at a certain ratio could clearly enhance tumor growth in vitro and in vivo compared with EGFRwt cells, thereby indicating that EGFRvIII cells promote tumor growth. Furthermore, we demonstrated that the EGFRvIII cells could support the growth of EGFRwt cells by secreting growth factors, thus acting as the principal source for maintaining tumor survival. F25P preproinsulin effectively reduced the concentrations of EGF, VEGF, and MMP-9 in the blood of tumor-bearing mice by competitively inhibiting the endoplasmic reticulum signal peptidase and increased the overall survival in orthotopic models. Taken together, our results provided an effective therapy of F25P preproinsulin in the EGFRvIII/wt heterogenic model. © 2016 Elsevier Ireland Ltd Source

Zhang T.,Tianjin Medical University | Zhang T.,Yale University | Pang C.,Tianjin Cancer Institute and Hospital | Li N.,Tianjin Medical University | And 2 more authors.
BMC Medicine | Year: 2013

Background: Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes.Methods: Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.Results: Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57).Conclusions: The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene-environment interaction in determining the risk of diabetic retinopathy. © 2013 Zhang et al; licensee BioMed Central Ltd. Source

Ren Y.,Tianjin Medical University | Ren Y.,Tianjin Neurological Institute | Zhou X.,Tianjin Cancer Institute and Hospital | Yang J.-J.,Tianjin Medical University | And 13 more authors.
Cancer Letters | Year: 2015

Paclitaxel (taxol) is a widely used chemo-drug for many solid tumors, while continual taxol treatment is revealed to stimulate tumor dissemination. We previously found that a small molecule inhibitor of miR-21, termed AC1MMYR2, had the potential to impair tumorigenesis and metastasis. The aim of this study was to investigate whether combining AC1MMYR2 with taxol could be explored as a means to limit tumor metastasis. Here we showed that abnormal activation of miR-21/CDK5 axis was associated with breast cancer lymph node metastasis, which was also contribute to high dose taxol-induced invasion and epithelial mesenchymal transition (EMT) in both breast cancer cell line MDA-MB-231 and glioblastoma cell line U87VIII. AC1MMYR2 attenuated CDK5 activity by functional targeting CDK5RAP1, CDK5 activator p39 and target p-FAKser732. A series of in vitro assays indicated that treatment of AC1MMYR2 combined with taxol suppressed tumor migration and invasion ability in both MDA-MB-231 and U87VIII cell. More importantly, combination therapy impaired high-dose taxol induced invadopodia, and EMT markers including β-catenin, E-cadherin and vimentin. Strikingly, a significant reduction of lung metastasis in mice was observed in the AC1MMYR2 plus taxol treatment. Taken together, our work demonstrated that AC1MMYR2 appeared to be a promising strategy in combating taxol induced cancer metastasis by targeting miR-21/CDK5 axis, which highlighted the potential for development of therapeutic modalities for better clinic taxol application. © 2015 Elsevier Ireland Ltd. Source

Liu Z.-J.,Tianjin Cancer Institute and Hospital | Wang J.,Tianjin Cancer Institute and Hospital | Wei X.-Y.,Chinese Institute of Basic Medical Sciences | Chen P.,Tianjin Cancer Institute and Hospital | And 4 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012

Purpose The present study was designed to elucidate the fluctuation of activated CECs (aCECs) during different therapies and to investigate their predictive value for efficacy of anti-angiogenesis and chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods Seventy-two patients were randomized into three arms, treated with concomitant NP (vinorelbine and cisplatin) and Rh-endostatin, Rh-endostatin followed by NP, and single NP up to a maximum of six cycles. Response, time to progression (TTP), and aCECs levels were observed. The correlation between aCECs and efficacy was analyzed. Results We found that TTP was 8.5 months in concomitant NP and Rh-endostatin versus 5.3 months in NP (p = 0.04) and 6.0 months in Rh-endostatin followed by NP. aCECs fluctuated during the therapeutic period, with a significantly high level from baseline on 8th day of Rh-endostatin followed by NP regimen, that is, when single Rh-endostatin was administered for 1 week, and upon completion of therapy in cases of progressive disease in each group (all p < 0.05). When TTP was longer than 10 months, aCECs count difference (DaCECs, the difference in the aCECs by post-therapeutic amount minus pretherapeutic amount) was reversely correlated to TTP (p = 0.003, r = -0.647). Conclusions An improved synergistic effect was achieved from concomitant NP and Rh-endostatin compared with Rh-endostatin followed by NP and single NP. aCECs increased when the disease was aggravated or single Rh-endostatin treatment of Rh-endostatin was administered, while they decreased when a clinical response to the combined therapy was obtained. Our results suggest ΔaCECs as an ideal marker to predict the response to Rh-endostatin combined with chemotherapy. © Springer-Verlag 2012. Source

Woloski-Wruble A.C.,Hebrew University of Jerusalem | Dekeyzer Ganz F.,Hebrew University of Jerusalem | Jiang Y.,Tianjin Cancer Institute and Hospital | Qiang W.-M.,Tianjin Cancer Institute and Hospital | Kadmon I.,Hebrew University of Jerusalem
Psycho-Oncology | Year: 2012

Objective: Cultural nuances may influence the interface between the cancer experience and marital issues, specifically for the partner. Most of the literature has focused on the woman's narrative or couple's adjustment to cancer in general. The purpose of this study was to describe and compare the marital relationship, sexuality, and marital adjustment of Israeli and Chinese husbands of women with breast cancer and the discussion of the health-care team concerning these issues. Methods: A convenience sample of 50 Chinese and 50 Israeli men, ages of 28-79 years, completed components of the Psychological Adjustment to Illness Scale, the Locke Wallace Adjustment Scale, and a background questionnaire. Results: The majority of husbands were in their first marriage. The average time since diagnosis was 16.7 months. No significant difference was found between the two groups on issues of marital relationship. Significant differences were found between Israeli and Chinese husbands on sexual interest, pleasure, and performance (p<0.05). Israeli husbands reported a significantly higher level of marital adjustment as opposed to the Chinese husbands (p = 0.006). Marital adjustment for both groups was significantly related only to perceived quality of the relationship (p<0.03). Conclusions: Significant cultural differences were found in sexuality variables with no differences discerned on marital relationship variables. Couple-based interventions for marital issues are a critical component of support for both partners. Culturally sensitive assessment and care of the spouse as well as the woman with breast cancer should be part of a holistic, comprehensive family care plan. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd. Source

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