Bladder cancer (BCa) is the most common malignant disease of the urinary tract system, yet the etiology is still poorly understood. Clinically, the majority of BCa patients progress to invasive disease at the final stage, leading to death. Previous investigations have demonstrated that matrix metal-loproteinases (MMPs) play irreplaceable roles in tumor cell extravasation and implantation. In addition, increasing numbers of reports provide evidence that MMPs, especially MMP2 and MMP9 are monitored by various signal transduction pathways targeting tumor metastasis. Seed-and-soil theory has called to attention the importance of the tumor microenvironment in disease progression. To that end, we previously reported the key role of hypoxia in BCa progression. Herein, we report the role of chemokines, specifically CXCL5, is involved in BCa development. Though it has been reported that CXCL5 promotes BCa metastasis and progression, the exact mechanisms are still unknown, necessitating the need for further investigation into the role of CXCL5 in BCa. In this study, IHC staining of BCa tumor sections showed elevated expression of CXCL5 in BCa, which correlated with disease stage. Our mechanistic studies show that CXCL5 contributes to BCa migration and invasion by binding to its receptor, CXCR2, leading to the upregulation of MMP2/MMP9 by activating PI3K/AKT signaling. This study offers vital evidence of how CXCL5 promotes BCa metastasis, and thus may potentially be used as a therapeutic target against BCa.

BackgroundIn the field of acupuncture research, the topic of acupoint specificity has received increasing attention, but no unified conclusion has been reached on whether or not acupoint specificity exists. Furthermore, the majority of previous acupuncture neuroimaging studies have been performed using healthy subjects. In this study, patients with migraine were used to investigate acupoint specificity.MethodsThirty patients with migraine were enrolled and randomized into three groups: Traditional Acupuncture Group (TAG), Control Acupuncture Group (CAG), and Migraine Group (MG). The TAG was treated by acupuncture stimulation at Waiguan (TE5), Yang Lingquan (GB34), and Fengchi (GB20). The CAG was treated at Touwei (ST8), Pianli (LI6), and Zusanli (ST36). The MG received no treatment. Positron emission tomography with computed tomography (PET-CT) was used to test for differences in brain activation between the TAG and CAG versus MG, respectively.ResultsTraditional acupuncture treatment was more effective for pain reduction than control acupuncture treatment. The TAG showed higher brain metabolism than the MG in the middle temporal cortex (MTC), orbital frontal cortex (OFC), insula, middle frontal gyrus, angular gyrus, post-cingulate cortex (PCC), the precuneus, and the middle cingulate cortex (MCC). Metabolism decreased in the parahippocampus, hippocampus, fusiform gyrus, postcentral gyrus, and cerebellum in the TAG compared with the MG. In the CAG, metabolism increased compared with the MG in the MTC, supratemporal gyrus, supramarginal gyrus, and MCC, whereas metabolism decreased in the cerebellum.ConclusionsAcupuncture stimulation of different points on similar body regions in migraine patients reduced pain and induced different levels of cerebral glucose metabolism in pain-related brain regions. These findings may support the functional specificity of migraine- treatment-related acupoint.Trial registrationThe number of our clinical trial registration is: ChiCTR-TRC-11001813, and the protocol and inclusion criteria have already been registered as ChiCTR-TRC-11001813.

BackgroundAcupuncture has analgesic effect to most pain conditions. Many neuroimaging studies were conducted to explore acupoint specificity in pain and other condition, but till now there is still discrepancy. Based on our previous finding, this study investigated the brain metabolism changes of acupuncture analgesia induced by sub-specific acupoint and non-acupoint stimulation.Methods30 migraineurs were included and randomly assigned to 3 groups: Acupuncture Group (AG), Sham Acupuncture Group (SAG) and Migraine Group (MG). In AG, a combination sub-specific points of Shaoyang meridians, Luxi (TE19), San Yangluo (TE8), and Xi Yangguan(GB33) has been stimulated with electroacupuncture, while non-acupoints for SAG were used and MG received no treatment. Positron emission tomography with computed tomography (PET-CT) was used to identify differences in brain glucose metabolism between groups.ResultsIn the AG, brain glucose metabolism increase compared with the MG was observed in the middle frontal gyrus, postcentral gyrus, the precuneus, parahippocampus, cerebellum and middle cingulate cortex (MCC), and decrease were observed in the left hemisphere of Middle Temporal Cortex (MTC).In the SAG, compared with MG, glucose metabolism increased in the poster cingulate cortex (PCC), insula, inferior temporal gyrus, MTC, superior temporal gyrus, postcentral gyrus, fusiform, inferior parietal lobe, superior parietal lobe, supramarginal gyrus, middle occipital lobe, angular and precuneus; while, decreased in cerebellum, parahippocampus.ConclusionsAcupuncture stimulation at both sub-specific acupoint and non-acupoint yields ameliorating effect to migraine pain, but with evidently differed central mechanism as measured by PET-CT. The pattern of brain glucose metabolism change in acupoint is pertinent and targeted, while in non-acupoint that was disordered and randomized. These finding may provide new perspectives into the validation of acupoint specificity, optimizing acupuncture analgesia and revealing central mechanism of acupuncture analgesia by neuroimaging measurement.Trial registrationThis trial was registered in the Chinese Clinical Trial Registry, with registration no. ChiCTR-TRC-11001813.

The aim of this study was to analyze the correlation between long noncoding RNA-HOX transcript antisense intergenic RNA (HOTAIR) and the clinical pathological characteristics and prognosis of oral squamous cell carcinoma (OSCC) and to evaluate the effect on cell growth. HOTAIR expressions in 50 surgically resected samples (including tumor and paracancerous tissues) collected from OSCC patients treated in our hospital from January 2009 to December 2010 were detected by real-time quantitative reverse transcription-PCR, and the relationship with clinical pathological characteristics and prognosis was analyzed. The effect of small interfering RNA treatment on cell growth (Tca8113, UM-1, and CAL-27 cells) was evaluated by MTT assay, and those on apoptosis and cell cycle were assessed by flow cytometry. HOTAIR was positively expressed in 45 samples (90 %). The expression level in tumor tissues was significantly higher than that in paracancerous tissues (t = 5.459, P < 0.01). Relative expression level of HOTAIR was correlated with tumor size and clinical stage (P < 0.05). More HOTAIR was expressed in OSCC cell lines than in normal oral epithelial cells. Interfering with HOTAIR expression in Tca8113 cells significantly decelerated cell growth, arrested cell cycle, and promoted apoptosis (P < 0.01). HOTAIR was highly expressed in OSCC tissues and facilitated the growth of OSCC cells, thus probably being an eligible molecular marker for OSCC diagnosis and prognosis determination.

The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin β3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas.