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ABSTRACT: Recent studies have indicated that Toll-like receptors (TLRs) are implicated in the development of chemoresistance in cancer cells. TLR4 has been shown to be highly expressed in prostate cancer cells and contributes to tumor cell survival and invasion. In this study, we aimed to investigate the role of TLR4 signaling in the chemoresistance of prostate cancer cells. We showed that ligation of TLR4 with lipopolysaccharide (LPS) abrogated docetaxel-induced growth suppression in PC-3 prostate cancer cells, with an increase in the half-maximal inhibitory concentration. Downregulation of TLR4 using small-interference RNA sensitized PC-3 cells to docetaxel-induced apoptosis as determined by annexin V staining and poly (ADP-ribose) polymerase cleavage, which was coupled with increased Bax expression and decreased Bcl-2. TLR4 ligation resulted in a marked increase in the phosphorylation of phosphatidylinositol 3-kinase (PI3-K) and Akt. The pretreatment with a PI3-K inhibitor LY294002 reduced LPS-mediated resistance to docetaxel, significantly decreasing the viability of PC-3 cells. Our data show that TLR4 ligation contributes to the chemosensitivity of prostate cancer cells, which at least partially involves the activation of the PI3-K/Akt pathway. Therefore, TLR4 signaling may represent a promising target for the improvement of chemotherapeutic efficacy in prostate cancer.
Cell Biology and Toxicology 06/2012; 28(4):269-77. · 2.51 Impact Factor
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ABSTRACT: ObjectiveThe aim of this study was to evaluate the effects and safety of brucea javanica oil, mitomycin and BCG for preventing postoperative
relapse of superficial bladder cancer through perfusion.
MethodsFrom July 2000 to May 2006, 178 patients with primary superficial bladder cancer (Ta-1, G1–2) were divided into three groups after operation in random: 57 patients in group A received perfusion of 60 mL 10% brucea
javanica oil, and 66 patients in group B received perfusion of 20 mg mitomycin while 55 patients in group C received perfusion
of 120 mg BCG. Eighteen perfusions per patient were carried out regularly a week after operation. Patients were followed up
for clinical, analytical and cystoscopic evaluations every 3 months for 2 years. The tumor relapse rates and side effects
after treatment were evaluated.
ResultsThe relapse rate was 14.04% (8/57), 34.85% (23/66) and 18.18% (10/55) in group A, B and C respectively. The relapse rate in
group A was obviously lower than that in group B (χ2 = 6.17, P < 0.05). Disease free interval in group A was significantly different from that in group B (F = 7.03, P < 0.05). Side effect in group A (12.28%) was observably lower than that in group B (43.94%) and group C (83.64%) (χ2
AB = 15.72, P < 0.01; χ2
AC = 55.34, P < 0.01).
ConclusionPerfusion of 10% brucea javanica oil after operation is safer and more effective in preventing superficial bladder tumour
relapse and worth for popularizing.
Key wordsbladder cancer–drug therapy–perfusion–regional–cancer relapse–local
The Chinese-German Journal of Clinical Oncology 04/2012; 10(4):228-231.
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ABSTRACT: PEX14 is an integral membrane protein essential for protein docking onto the peroxisomes and is a bi-functional protein capable of acting as a transcriptional co-repressor and a polypeptide transport modulator. Further studies showed that PEX14 is the sole peroxin that has a unique dual function in peroxisome formation and selective degradation. Its RNA transcripts are ubiquitously expressed; there is, however, no data on the expression profiles of PEX14 at the protein level due to a lack of MAbs suitable for immunohistochemical staining, thus hindering studies on its functions. In the present study, we generated one MAb that could be used in immunocytochemistry and immunohistochemistry and investigated PEX14 expression in normal and malignant human tissues. In contrast to the ubiquitous expression of its RNA transcripts, there is no PEX14 protein expression in normal human tissue, including liver, spleen, lung, rectum, brain, prostate, breast, ovary, and stomach. Protein expression of PEX14 was dramatically upregulated in some malignancies. Presented here are the first data on the expression profiles of PEX14 at the protein level, which will further our understanding of its functions.
Hybridoma (2005) 04/2012; 31(2):142-5. · 0.42 Impact Factor
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ABSTRACT: Previous work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.
Findings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3'UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.
These findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.
PLoS ONE 01/2010; 5(4):e10147. · 4.09 Impact Factor
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Longxin Wang,
Weihong Wen,
Jianlin Yuan,
Brian Helfand,
Yu Li,
Changhong Shi,
Feng Tian,
Jia Zheng, Fuli Wang,
Lin Chen,
Lili Liang,
Liqun Zhou,
Chung Lee,
Zhinan Chen,
Yinglu Guo,
He Wang,
Qiang Zhang,
Weijun Qin
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ABSTRACT: Transforming growth factor-beta (TGF-beta) is a potent immunosuppressor that has been associated with tumor evasion from the host immune surveillance and, thus, tumor progression. We tested a novel immunotherapy for human renal cell cancer (RCC) using a technique that involves the adoptive transfer of autologous tumor-reactive, TGF-beta-insensitive CD8(+) T cells into human RCC-challenged immunodeficient mice to identify its potent antitumor responses.
The present study was conducted using a one-to-one adoptive transfer strategy to treat tumor-bearing severe combined immunodeficient (SCID/beige) mouse. The SCID/beige mice were humanized with peripheral blood mononuclear cells from patients with RCC (Hu-PBMC-SCID) before adoptive transfer. Autologous CD8(+) T cells were expanded ex vivo using autologous patient's dendritic cells pulsed with the tumor lysate and rendered TGF-beta insensitive by dominant-negative TGF-beta type II receptor. In addition, human RCC cell lines were generated using patients' tumor cells injected into SCID/beige mice.
Using flow cytometry analysis, we confirmed the expression of the tumor-reactive, TGF-beta-insensitive CD8(+) T cells were the effector CD8(+) cells (CD27(-)CDRA(+)). Adoptive transfer of autologous TGF-beta-insensitive CD8(+) T cells into tumor-bearing Hu-PBMC-SCID mice induced robust tumor-specific CTL responses in vitro, were associated with tumor apoptosis, suppressed lung metastasis, and prolonged survival times in vivo.
The one-to-one adoptive transfer strategy is an ideal in vivo murine model for studying the relationship between TGF-beta and immunosurveillance in RCC in vivo. Furthermore, this technique may offer the promise of a novel therapeutic option for the treatment of human patients with RCC.
Clinical Cancer Research 12/2009; 16(1):164-73. · 7.74 Impact Factor
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ABSTRACT: Preprocessing and correction of mixture spectra have been an important issue with regard to the removal of undesired systematic variation due to variations in environmental, instrumental, or sample conditions. In this article, a new robust calibration modeling strategy is proposed on the basis of independent component analysis (ICA). It aims at separating the interference-subject parasitic subspace from the interference-immune common subspace among all considered cases. The common subspace is further divided into two orthogonal parts according to their relationship with quality: one is quality-irrelevant and the other is quality-informative, in which, only the second part is employed for quality prediction. Focusing on each subspace, it identifies distinct types of underlying source components underlying different spectra subspaces, analyzes their characteristics and roles, and accordingly models them for different applications, respectively. This approach provides a comprehensive insight into the inherent nature of interference-subject mixture spectra. Furthermore, several model statistics are defined to give quantitative indication on the effectiveness of the correction strategy. The feasibility and performance of the proposed method are illustrated with data from laboratory experiments. © 2009 American Institute of Chemical Engineers AIChE J, 2010
AIChE Journal 08/2009; 56(1):196 - 206. · 2.26 Impact Factor
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ABSTRACT: Human BAP31 is a 28 kDa polytopic integral protein of the ER and part of a large BAP hetero-oligomeric complex that includes the related BAP29 protein and connections to actomyosin. BAP31 interacts with mIgD, cellubrevin, major histocompatibility complex class I, and BCL-2/BCL-X(L), and plays an important role in regulating the egress of these proteins and in apoptosis. Northern blot analyses have revealed BAP31 RNA transcripts in many tissues, including thymus, spleen, brain, kidney, testis, liver, and lung. However, prominent BAP31 protein expression analyzed by immunohistochemistry is restricted to a minority of cells in normal human tissue. Further studies should be made to verify the expression profiles of BAP31 in the protein level. Production of high affinity MAbs suitable for immunohistochemical staining has lagged. Here we generate a set of MAbs that could be used in Western blot, immunoprecipitation, and immunocytochemistry, providing a new powerful tool for investigation of expression profile of BAP31 protein and furthers the study of BAP31 functions.
Hybridoma (2005) 07/2009; 28(3):177-81. · 0.42 Impact Factor
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ABSTRACT: We present a technology to make ultrahigh spacing tissue arrays (USTA) which facilitates screening hybridoma by immunohistochemistry, results in easier performance of staining and image analysis, minimal sample mixed-up and less bookkeeping efforts. 32 array cores are designated a 4x8 microarray, leaving 4 mm spacing between two adjacent array elements. After separated each array spot with PAP pen, one USTA is sufficient for testing of supernatants from 32 different hybridomas.
Journal of immunological methods 03/2009; · 2.35 Impact Factor
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Weijun Qin,
Feng Tian, Fuli Wang,
Bin Song,
He Wang,
Qiang Zhang,
Borko Jovanovic,
Lili Liang,
Yinglu Guo,
Norm Smith,
Chung Lee
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ABSTRACT: To test, using a mouse renal cancer, Renca, whether adoptive transfer of tumor-reactive transforming growth factor (TGF)-beta-insensitive cytolytic T cells can inhibit tumor progression.
Cytolytic T cells were isolated from the spleen of male Balb/c mice repeatedly primed with irradiated Renca cells. They were expanded ex vivo and were rendered TGF-beta-insensitive by infecting with a retrovirus containing dominant negative TGF-beta type II receptor.
These tumor reactive TGF-beta-insensitive cytolytic T cells showed a specific and robust tumor killing activity against Renca cells, but not irrelevant cells, using an in vitro cytotoxic assay. Adoptive transfer of cytolytic T cells was performed in mice 10 days after they were challenged with Renca cells (5 x 10(5)) by tail vein injection. At 30 days after the adoptive transfer, the pulmonary tumor counts in mice who had received TGF-beta-insensitive cytolytic T cells (mean +/- standard deviation 130 +/- 140) was significantly less than those in mice that had received TGF-beta-sensitive cytolytic T cells (305 +/- 60) or in mice had received naive cytolytic T cells (375 +/- 50; P < .01). Kaplan-Meier survival analysis indicated that mice that had received adoptive transfer of TGF-beta-insensitive cytolytic T cells had a significantly greater rate of survival (75%) compared with mice that had received TGF-beta-sensitive cytolytic T cells (35%) or naive cytolytic T cells (15%), respectively (P < .05).
These results suggest that adoptive transfer of tumor-reactive TGF-beta-insensitive cytolytic T cells can warrant consideration for renal cell cancer immunotherapy.
Urology 09/2008; 72(4):943-7. · 2.43 Impact Factor
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Feng Tian,
Longxin Wang,
Weijun Qin, Fuli Wang,
Bin Song,
Yu Li,
Weihong Wen,
Zheng Zhang,
Kaichang Zhu,
Qiang Zhang,
Chung Lee,
Weide Zhong,
Yinglu Guo,
He Wang
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ABSTRACT: Dendritic cells (DCs) have been widely used as cancer vaccines. However, their functional abilities have often been suppressed by tumor-secreted immunosuppressants such as transforming growth factor-beta (TGF-beta). We developed a new strategy using a TGF-beta insensitive DC as cancer vaccine. The effect of this vaccine was tested in a murine pulmonary metastases model of renal carcinoma (Renca). Tumor lysate-pulsed DCs (TP-DCs) were infected with retrovirus containing gene of dominant negative TGF-beta type II receptor (TbetaRIIDN) and thus made TGF-beta insensitive. Vaccination of the mice bearing Renca pulmonary metastases with the TbetaRIIDN TP-DC induced powerful tumor-specific cytotoxic T lymphocyte (CTL) responses, suppressed pulmonary metastases, and prolonged survival times. These results suggest TGF-beta-insensitive TP-DC vaccine can be used to enhance the antitumor efficacy of DC vaccine.
Cancer letters 08/2008; 271(2):333-41. · 4.86 Impact Factor
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Geng Zhang,
He Wang, Fuli Wang,
Lei Yu,
Xiaojian Yang,
Junhua Meng,
Weijun Qin,
Guojun Wu,
Jianhua Li,
Angang Yang,
Yu Zhou,
Rui Zhang
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ABSTRACT: Steroid refractory acute rejection (SRAR) is a major vital factor in renal transplantation recipients. The pathogenesis of SRAR may involve both immune and non-immune mechanisms. A decreased renal allograft function has also been associated with increased activity of renin-angiotensin-aldosterone system (RAS), which may be genetically determined. A total 206 renal transplant recipients, 116 males and 90 females, were included. The effects of gene polymorphisms of the four components of RAS including angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin type 1 receptor (AT1R), and aldosterone synthase (CYP11B2) were investigated in 19 cases of renal transplant patients with SRAR. The association between SRAR and the activating antibodies targeting the AT1R were also investigated. Genotyping was performed for the M235T-AGT, the I/D-ACE, the A1166C-AT1R, and the -344T/C-CYP11B2 gene polymorphisms using polymerase chain reaction. Our results showed that renal allograft recipients with SRAR had significantly higher occurrences of the DD genotype of ACE and CC genotype of AT1R than recipients without SRAR. The other genetic polymorphisms of the RAS were not associated with SRAR. Activating antibodies targeting the AT1R were detected in the sera from 14 SRAR victims with malignant hypertension and without anti-HLA antibodies. This study provides evidence that determination before transplantation of the polymorphism of the gene encoding components of RAS may help identify patients who are at risk for SRAR. The detection of the antibodies of AT1R may contribute to the prevention of SRAR.
The Tohoku Journal of Experimental Medicine 12/2007; 213(3):203-14. · 1.24 Impact Factor
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ABSTRACT: CD147, also named extracelluar matrix metalloproteinase inducer (EMMPRIN), has been proved to be involved in the invasion and metastasis processes of tumor cells in many types of cancers. To determine the role of CD147 in the invasiveness properties of prostate cancer, we successfully downregulated CD147 by RNA interference (RNAi) technology, in PC-3 cell line at high level of CD147 expression. PC-3 cells were transfected with a pSilencer 4.1-CMV neo Vector coding for an RNA composed of two identical 19-nucleotide sequence motifs in an inverted orientation, separated by a 9-bp spacer to form a hairpin dsRNA capable of mediating target CD147 inhibition. Gelatin zymography was employed to determine the effect on reducing secretions of MMP-2 and MMP-9 of the transfected cells. Matrigel invasion assay was performed to evaluate the invasion ability of PC-3 cells in vitro. Our results showed that CD147 expression was significantly inhibited by small interfering RNAs (siRNA) transfectants in PC-3 cells at mRNA and protein levels, which resulted in dramatic reduction of invasion ability in tumor cells. Moreover, downregulation of CD147 resulted in reducing secretions of MMP-2, MMP-9. Taken together, CD147 downregulation by RNAi technology decreases the invasive capability of prostate cancer cells, demonstrating that stable expression of siRNA CD147 could potentially be an experimental approach for prostate cancer gene therapy.
Cancer biology & therapy 07/2006; 5(6):608-14. · 2.64 Impact Factor
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AIChE Journal 01/2004; 50(1):255 - 259. · 2.26 Impact Factor
