| 1. |
- Hua, Dong, et al.
(författare)
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Small interfering RNA-directed targeting of toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity
- 2009
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 46:15, s. 2876-2884
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Tidskriftsartikel (refereegranskat)abstract
- A major cause of tumor treatment failure is cancer cell metastasis. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we investigated the biological roles of TLR4 in prostate metastatic cell invasion and survival, and the potential of gene silencing of TLR4 using small interfering RNA (siRNA) for treatment of cancer. In cultured human prostate cancer cell lines, TLR4 were higher PC3 and DU145 as compared with the poorly metastatic LNCaP indicating that up-regulation of TLR4 was positively correlated with metastasis of tumor cell. In the highly metastatic cancer cell PC3, gene silencing of TLR4 using siRNA significantly inhibited TLR4 mRNA expression and protein level. Knockdown of TLR4 in PC3 cells resulted in a dramatic reduction of tumor cell migration and invasion as indicated by a Matrigel invasion assay. Furthermore, TLR4 siRNA suppressed cell viability and ultimately caused the induction of apoptotic cell death. The effects were associated with abrogating TLR4-mediated signaling to downstream target molecules such as myeloid differentiation factor 88 (MyD88), adaptor-inducing IFN-beta (TRIF), and interferon regulatory factor-1 (IRF-1). In a mouse prostate cancer model, administration with the plasmid construct expressing siRNA for TLR4 obviously inhibited established tumor growth and survival. These studies revealed evidence of a multifaceted signaling network operating downstream of TLR4-mediated tumor cell invasion, proliferation, and survival. Thus, RNA interference-directed targeting of TLR4 may raise the potential of its application for cancer therapy.
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| 2. |
- Liu, Yang, et al.
(författare)
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Reduction of p120ctn isoforms 1 and 3 is significantly associated with metastatic progression of human lung cancer
- 2007
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 115:7, s. 848-856
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Tidskriftsartikel (refereegranskat)abstract
- P120-catenin plays an important role in cell adhesion and signalling transduction though the function of its isoforms is unclear. The aim of this study was to examine the expression of p120-catenin isoforms in lung cancer and investigate their relationship to clinicopathological factors in lung squamous cell carcinomas (SCCs) and adenocarcinomas. The expression patterns of p120-catenin in lung cancer tissues and lung cancer cells were examined by p120-catenin immunofluorescence, Western blot, and reverse transcription- polymerase chain reaction (RT-PCR). Clear and continuous red fluorescence of p120-catenin is displayed at the cell membrane of corresponding normal bronchial epithelial cells, but not in lung cancer tissues that show reduction or absence of membrane expression of p120-catenin or cytoplasmic accumulation of p120-catenin. Compared with corresponding normal lung tissues, lung cancer tissues have significantly lower levels of p120-catenin proteins (P<0.001) and mRNA (P<0.001). The isoforms 1 (120 kD) and 3 (100 kD) proteins were major isoforms of p120-catenin expressed in normal lung tissues, which were significantly reduced in lung cancer samples (P=0.001 and P<0.001, respectively). The mRNA of p120-catenin isoforms 1.2, 1.3, 2.3, 3.1 and 3.3 was detected in corresponding normal lung tissues, but was significantly absent in lung cancer samples (P<0.001 and P=0.001, respectively). Furthermore, p120-catenin isoform 1 is negatively associated - whereas p120-catenin isoform 3 is positively associated - with lymph node metastasis. We conclude that reductions of isoforms 1 and 3 may play different roles in metastatic progression of human lung cancer. © Apmis 2007.
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| 3. |
- Su, Min, et al.
(författare)
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Temporal trends of esophageal cancer during 1995-2004 in Nanao Island, an extremely high-risk area in China
- 2007
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 22:1, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of our study was to investigate the temporal malignant tumor incidence rates among the 70,000 residents at the relatively isolated Nanao Island in South China Sea. The data on all malignant tumor cases from Nanao Cancer Registry during 1995-2004 were coded, computerized, and analyzed using the software SPSS10.0. The tumor incident cases, crude incident rate, age-standardized incidence rate, their sex distribution and temporal trend were assessed. A total of 1450 new cancer cases (990 males and 460 females) were identified. The annual average age-standardized incidence rate (ASR) of malignant tumors was 208.18/100,000. The age-standardized incidence rate of the ten leading cancers in both sexes combined per 100,000 population were 74.47 for esophageal cancer (EC), 34.81 for cardiac cancer (CC), 25.66 for liver cancer, 26.01 for lung cancer, 18.52 for stomach cancer, 4.45 for nasopharyngeal cancer, 3.91 for breast cancer, 2.53 for colon/rectum cancer, 2.45 for bladder cancer and 1.92 for pancreatic cancer. These ten types of cancers make up to 93% of all cancer cases, with EC and CC being the most prevalent and making up 52% of the total cases. The incidence rates of esophagus, liver, lung, breast, nasopharyngeal, and colon/rectum cancers showed increasing trends during the period from 1995 to 2004 in Nanao Island. Astounding the EC ASR were 72-150/100,000 among male and 26-64/100,000 among female in Nanao Island during 1995-2004. The EC incidence rate in Nanao population is among the highest across the world, which suggests that there are potential genetic and/or environmental factors affecting this particular population.
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| 4. |
- Zhang, Fan, et al.
(författare)
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VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:15, s. 6152-6157
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Tidskriftsartikel (refereegranskat)abstract
- VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
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