Hepatocellular carcinoma is a highly lethal cancer that typically has poor prognosis. Prognostic markers can help in its clinical management and in understanding the biology of poor prognosis. Through an earlier gene expression study, we identified N-Myc downregulated gene 1 (NDRG1) to be significantly highly expressed in hepatocellular carcinoma compared to nontumor liver. As NDRG1 is a differentiation-related gene with putative metastasis suppressor activity, we investigated the clinical significance of its overexpression. Quantitative realtime polymerase chain reaction using an independent set of patient samples confirmed the significant overexpression of NDRG1 in hepatocellular carcinoma compared to nontumor liver samples (Po0.001). Additionally, high levels of NDRG1 transcript correlated with shorter overall survival (Po0.001), late tumor stage (P ¼ 0.001), vascular invasion (P ¼ 0.003), large tumor size (P ¼ 0.011), and high Edmondson-Steiner histological grade (P ¼ 0.005). Using immunohistochemistry, NDRG1 protein was found to be significantly overexpressed in hepatocellular carcinoma samples compared to nontumor liver or cirrhotic and benign liver lesions (Po0.001). Among the hepatocellular carcinoma samples, those which are moderately and poorly differentiated express higher levels of NDRG1 protein than those which are well-differentiated (Po0.005). Additionally, hepatocellular carcinomas with vascular invasion also express elevated levels of NDRG1 protein compared to those without vascular invasion (significant at Po0.005). Our results suggest NDRG1 to be a likely tumor marker for hepatocellular carcinoma, the overexpression of which is correlated with tumor differentiation, vascular invasion, and overall survival. Its significantly elevated expression in hepatocellular carcinoma could be a useful indicator of tumor aggressiveness and therefore patient prognosis. Modern Pathology (2007) 20, 76-83.

Objective We aimed to investigate the effectiveness of acupoint polyglactin 910 (PGLA) embedding in patients with cervical spondylotic radiculopathy (CSR). Methods A total of 102 CSR patients with neck and shoulder pain were recruited and assigned randomly into three groups: the sham acupoint embedding (SAE) group, the middle-layer acupoint PGLA embedding (MAPE) group, and the deep-layer acupoint PGLA embedding (DAPE) group. The primary outcomes were Visual Analog Scale (VAS) scores showing the analgesic effects of treatment. Secondary outcomes included clinical symptoms (evaluated by the Yasuhisa Tanaka 20 (YT-20) score and the neck disability index (NDI)) and patient health status (evaluated by the 36-item short-form survey (SF-36)) as reported in the trial. Results Compared with the SAE group, VAS scores were significantly reduced at 1, 2, 3, 4, and 10 weeks after the first treatment in both the DAPE and MAPE groups (P < 0.001). Moreover, there were statistically significant increases in the weekly YT-20 scores and significant reductions of the weekly NDI scores compared with baseline values in both the DAPE and MAPE groups (P < 0.001). Compared with baseline values, both the physical component summary (PCS) and the mental component summary scores of the SF-36 at 2, 3, 4, and 10 weeks were significantly higher in the DAPE and MAPE groups (P < 0.001). There were significant lower VAS scores (P < 0.01), higher PCS scores (P < 0.05) at 3 weeks, and lower NDI scores (P < 0.05) at 4 weeks in the DAPE group compared with the MAPE group. Conclusions Both DAPE and MAPE showed significant and long-lasting effects on alleviating pain and improving clinical symptoms as well as quality of life in CSR patients with neck and shoulder pain. A more intense effect was seen in the DAPE group compared with the MAPE group.

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Cervical cancer (CC) is a prevalent malignancy in women, with the feature of metastasis and easy recurrence is responsible for a large proportion of global cancer deaths. Radiotherapy is one of the common treatment tools for CC patients with unresectable tumors. However, radio-resistance in patients could be a major reason for recurrence. Therefore, it is of significance to tunnel the molecular mechanism of radio-resistance in CC. MicroRNAs (miRNAs) are increasingly reported in the regulation of cancer progression and cellular response to radiotherapy and chemotherapy. miR-4429 is a newly discovered miRNA acting as a tumor-suppressor gene in multiple cancers, but its function in CC has never been explored yet. The current study tried to explore the role of miR-4429 in cell radio-sensitivity in CC.First, we validated the downregulation of miR-4429 in CC cells. Importantly, the association of miR-4429 with radio-resistance was validated by identifying the downregulation of miR-4429 in radio-resistant CC cells. Gain-and loss-of-function assays validated that miR-4429 sensitized CC cells to irradiation. Through bioinformatics tools, RAD51 recombinase (RAD51) was identified to be a target for miR-4429. RAD51 is known to be a crucial regulator for DNA damage repair and has been reported to influence cell radio-resistance in cancers, including in CC. Luciferase reporter assay confirmed the interaction between miR-4429 and RAD51. Finally, rescue assays indicated that miR-4429 promoted CC cell radio-sensitivity through RAD51. Consequently, our study showed that miR-4429 sensitized CC cells to irradiation by targeting RAD51, providing a potential therapeutic target for CC patients. K E Y W O R D Scervical cancer, miR-4429, RAD51, radio-resistance

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specifi c diagnostic markers of HCC. Alpha-fetoprotein (AFP), the currently used HCC marker, misses 30%-50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48) and patients with chronic hepatitis B or C viral infections (n = 19) (both of which are the major risk factors of HCC). We identifi ed 7 proteins that signifi cantly differentiate HCC patients from hepatitis patients (p Ͻ 0.05) (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1). Importantly, we also identifi ed 8 proteins that signifi cantly differentiate HCC patients with 'normal' levels of AFP (Ͻ20 ng/ml) from hepatitis patients (p Ͻ 0.05) (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL). These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were signifi cantly higher in the HCC group (p = 0.020). In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identifi ed HCC diagnostic markers needs to be systematically evaluated.