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Li L.,University of Michigan | Li L.,PLA Fourth Military Medical University | Hao X.,University of Michigan | Hao X.,Hainan Medical College Hospital | And 12 more authors.
Gastroenterology | Year: 2014

Background & Aims CD44s is a surface marker of tumor-initiating cells (TICs); high tumor levels correlate with metastasis and recurrence, as well as poor outcomes for patients. Monoclonal antibodies against CD44s might eliminate TICs with minimal toxicity. This strategy is unclear for treatment of pancreatic cancer, and little is known about how anti-CD44s affect pancreatic cancer initiation or recurrence after radiotherapy. Methods One hundred ninety-two pairs of human pancreatic adenocarcinoma and adjacent nontumor pancreatic tissues were collected from patients undergoing surgery. We measured CD44s levels in tissue samples and pancreatic cancer cell lines by immunohistochemistry, real-time polymerase chain reaction, and immunoblot; levels were correlated with patient survival times. We studied the effects of anti-CD44s in mice with human pancreatic tumor xenografts and used flow cytometry to determine the effects on TICs. Changes in CD44s signaling were examined by real-time polymerase chain reaction, immunoblot, reporter assay, and in vitro tumorsphere formation assays. Results Levels of CD44s were significantly higher in pancreatic cancer than adjacent nontumor tissues. Patients whose tumors expressed high levels of CD44s had a median survival of 10 months compared with >43 months for those with low levels. Anti-CD44s reduced growth, metastasis, and postradiation recurrence of pancreatic xenograft tumors in mice. The antibody reduced the number of TICs in cultured pancreatic cancer cells and xenograft tumors, as well as their tumorigenicity. In cultured pancreatic cancer cell lines, anti-CD44s down-regulated the stem cell self-renewal genes Nanog, Sox-2, and Rex-1 and inhibited signal transducer and activator of transcription 3-mediated cell proliferation and survival signaling. Conclusions The TIC marker CD44s is up-regulated in human pancreatic tumors and associated with patient survival time. CD44s is required for initiation, growth, metastasis, and postradiation recurrence of xenograft tumors in mice. Anti-CD44s eliminated bulk tumor cells as well as TICs from the tumors. Strategies to target CD44s cab be developed to block pancreatic tumor formation and post-radiotherapy recurrence in patients. © 2014 by the AGA Institute.


Liu H.,Dalian Medical University | Wu H.,Dalian Medical University | Wu H.,Hainan Medical College Hospital | Kuwada T.,Nihon University | And 8 more authors.
Journal of Hard Tissue Biology | Year: 2012

Signaling pathways have been shown to participate in the process of Retinoic acid (RA) - induced cleft palate (CP). In our current study, the signaling molecules of GSK-3β, Fzd3 and β-TrCP, which all relate with Wnt pathway, were screened from the palate tissues of the RA-induced CP in mice by the Gene-chip Technology. But, their expression pattern and level in palates during perinatal stages have not been known yet. In the studies, mRNA level of GSK-3β, Fzd3 and β-TrCP were detected by quantitative real-time PCR, and showed significant difference between the Embryonic day 18 (ED18) before birth and Postnatal day 0 (PD0) after birth, as well as between the RAinduced CP and wild type during the perinatal stage, respectively. And the localization pattern of GSK-3β, Fzd3 and β-TrCP proteins in palates was also characterized. Our data indicates that the Wnt signaling pathway may involve in the RA-induced cleft palate during peirnatal stage. © 2012 The Hard Tissue Biology Network Association Printed in Japan, All rights reserved.


You X.-G.,Hainan Medical College Hospital | Tu R.,Hainan Medical College Hospital | Peng M.-L.,Northwest University, China | Bai Y.-J.,Hainan Medical College Hospital | And 4 more authors.
Contrast Media and Molecular Imaging | Year: 2014

A new method for imaging the tumor human vascular endothelial growth factor 165 (VEGF 165) is presented. A magnetic resonance imaging (MRI) probe was prepared by crosslinking ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to the aptamer for tumor vascular endothelial growth factor 165 (VEGF165-aptamer). The molecular probe was evaluated for its in vitro and in vivo activities toward VEGF165. Enzyme-linked immunosorbent assay showed that the VEGF165-aptamer-USPIO nanoparticles conjugate specifically binds to VEGF165 in vitro. A cell proliferation test showed that VEGF165-aptamer-USPIO seems to block the proliferation of human umbilical vein endothelial cells induced by free VEGF165, suggesting that VEGF165 is an effective target of this molecular probe. In xenograft mice carrying liver cancer that expresses VEGF165, T2-weighted imaging of the tumor displayed marked negative enhancement 3h after the intravenous administration of VEGF165-aptamer-USPIO. The enhancement disappeared 6h after administration of the probe. These results suggest the targeted imaging effect of VEGF165-aptamer-USPIO probe in vivo for VEGF165-expressing tumors. This is the first report of a targeted MRI molecular probe based on USPIO and VEGF165-aptamer. © 2014 John Wiley & Sons, Ltd.


Lin S.,Hainan Medical College Hospital | Zhang J.,Hainan Medical College Hospital | Huang L.,Hainan Medical College Hospital | Guan Y.,Hainan Medical College Hospital | Zheng E.,Hainan Medical College Hospital
Chinese Journal of Clinical Oncology | Year: 2012

Objective: This study aims to evaluate ultrasound imaging and ultrasound elastography of benign and malignant thyroid nodules in the differential diagnosis. Methods: A total of 164 benign and malignant thyroid nodules confirmed using pathology, ultrasound contrast, and elasticity imaging characteristics were analyzed to assess the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic coincidence rate. Results: The 164 thyroid nodules included 96 benign lesions and 68 malignant lesions. After the injection of contrast medium, the benign nodules enhanced the surrounding glands later than the peripheral gland dissection. Majority of the nodules exhibited peripheral ring enhancement. The malignant nodules were mostly low-enhanced and uneven enhanced echo as early as the dissipation of the surrounding thyroid tissue. The contrast sensitivity, specificity, positive predictive value, and negative predictive values of ultrasound were 91.18%, 93.75%, 91.18%, and 93.75%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive values of elastrography were 88.24%, 91.67%, 88.24%, and 91.67%, respectively. The contrast sensitivity, specificity, positive predictive value, and negative predictive values of ultrasound combined with elastography were 97.06%, 85.42%, 82.50%, and 97.62%, respectively. Conclusion: Ultrasound imaging and elastography have a high value for differential diagnosis of benign and malignant thyroid nodules, and the combination of the two methods can improve the diagnosis rate.

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