Lentivirus-mediated RNA interference targeting the ObR gene in human breast cancer MCF-7 cells in a nude mouse xenograft model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There is a significant association between obesity and breast cancer, which is possibly due to the expression of leptin. Therefore, it is important to clarify the role of leptin/ObR (leptin receptor) signaling during the progression of human breast cancer.</p><p><b>METHODS</b>Nude mice with xenografts of MCF-7 human breast cancer cells were administered recombinant human leptin subcutaneous via injection around the tumor site. Mice in the experimental group were intratumorally injected with ObR-RNAi-lentivirus, while negative control group mice were injected with the same dose of negative-lentivirus. Tumor size was blindly measured every other day, and mRNA and protein expression levels of ObR, estrogen receptor a (ERa), and vascular endothelial growth factor (VEGF) for each group were determined.</p><p><b>RESULTS</b>Knockdown of ObR-treated xenografted nude mice with a high leptin microenvironment was successfully established. Local injection of ObR-RNAi-lentivirus significantly suppressed the established tumor growth in nude mice. ObR level was significantly lower in the experimental group than in the negative control group, while the amounts of ERa and VEGF expression were significantly lower in the leptin group than in the control group (P < 0.01 for all).</p><p><b>CONCLUSIONS</b>Inhibition of leptin/ObR signaling is essential to breast cancer proliferation and possible crosstalk between ObR and ERa, and VEGF, and may lead to novel therapeutic treatments aiming at targeting ObR in breast cancers.</p>

Clinical significance of PHPT1 protein expression in lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In our previous studies, we found the expression of 14-kD phosphohistidine phosphatase (PHPT1) was associated with lung cancer cells migration and invasion, and PHPT1 mRNA expression level in lung cancer tissues clinically correlated with lymph node metastasis. In the present study, we aimed to further investigate the expression of PHPT1 protein in lung cancer.</p><p><b>METHODS</b>Expression of PHPT1 protein in tissue samples from 146 lung cancers and 30 normal tissues adjacent to lung cancers was assessed using immunohistochemical method. Fisher's exact test was used to analyze expression patterns of PHPT1 protein in these tissue types. Meanwhile, we studied the correlation between expression of PHPT1 protein and clinicopathological features in lung cancer.</p><p><b>RESULTS</b>Significantly higher expression levels of PHPT1 protein were found in lung cancer samples (53.42%) than in normal tissues adjacent to lung cancer (23.33%) (P = 0.003). Fisher's exact test showed that lung cancer stage positively correlated with expression of PHPT1 protein (P = 0.02), and lung cancer samples with lymph node metastasis showed higher PHPT1 protein expression (P = 0.016) than the samples without lymph node metastasis.</p><p><b>CONCLUSIONS</b>The results of this study agree with findings from our previous study of PHPT1 mRNA expression in lung cancer tissues, and strongly suggest that PHPT1 protein is closely associated with the carcinogenesis and metastasis of lung cancer. Thus, therapy targeting PHPT1 (inhibition or silencing) could be potentially benefited for lung cancer patients.</p>