BACKGROUND: The seventh edition of the American Joint Committee on Cancer staging system considers tumor location as a factor in staging esophageal squamous cell carcinoma (ESCC). However, more data are essential to test its efficacy. The purpose of this study is to assess whether tumor location should be included as a factor in staging of thoracic ESCC in Chinese patients. METHODS: A retrospective review of 1,220 patients with ESCC who underwent complete resection between December 1996 and December 2008 was conducted. Survival was calculated by the Kaplan-Meier method, and the log-rank test was used to assess survival differences between groups. Subgroup analysis and the Cox proportional hazards model were used to further determine the impact of tumor location on overall survival. RESULTS: The median survival times for patients with ESCC in the upper third, middle third, and lower third of the esophagus were 45.1 months, 62.9 months, and 39.2 months, respectively, with corresponding 5-year survival rates of 44.8%, 50.5%, and 45.6%, respectively (p = 0.191). Subgroup analysis also demonstrated that tumor location did not determine survival prognosis. Multivariate Cox regression analysis suggested that being female (p = 0.001), being young (p < 0.001), having a lower grade of cell differentiation (p = 0.030), T category (p < 0.001), and N category (p < 0.001) were independent factors favoring overall survival, whereas tumor location (p = 0.295) and surgical approaches (p = 0.521) were not independent factors impacting prognosis. CONCLUSIONS: Staging of ESCC in the Chinese population should be simplified by omitting tumor location as a variable. More data from Asian populations are warranted to verify these results.

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.

PCR-RFLP was used to analyze the polymorphisms of MC4R, LEP, H-FABP genes in a swine breed composite (DIV(2)) and 4 swine breeds (Yorkshire, Landrace, Meishan, Bamei). The association study of these polymorphisms with several economic traits was carried out on a DIV(2) population. The results obtained showed that MC4R/TaqI genotype had an effect for average backfat thickness (P < 0.05) and lean meat percentage (P < 0.05). At locus LEP/HinfI animals of AA genotype had lower test daily gain than that of BB (P < 0.01) or AB genotype (P < 0.05). At the H-FABP/HaeIII locus lean meat percentage of the individuals with genotype DD were higher than that with genotype dd (P < 0.05). Linkage disequilibrium analysis among MC4R, LEP and H-FABP revealed that these genes were independent. This represented two or more genes that could be combined together within one genotype in order to facilitate breeding for objective traits. In addition, a method allowing simultaneous detection of fragments of MC4R and LEP gene was developed.

NKX3.1, which is a prostate-specific homeobox gene, plays an important role in prostate cancer and usually functions as a tumour suppressor gene. In this study, we investigated the inhibitory effect of NKX3.1 on insulin-like growth factor (IGF)-1R expression and its downstream signalling pathway in PC3 cells. PC3 cells were stably transfected with NKX3.1 expression plasmid (pcDNA3.1-NKX3.1) or vector plasmid (pcDNA3.1+). The IGF-IR mRNA and protein expression levels were assessed in PC3-NKX3.1 transfectants by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The expression and activation of IGF-1/IGF-1R downstream signalling targets were examined by Western blotting and luciferase reporter assay. The cells were subsequently treated with relevant concentrations of IGF-1. The effect of IGF-1 on cell growth was examined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay and flow cytometry analysis. A significant suppression of IGF-1R mRNA and protein expression was observed after forced expression of NKX3.1 in PC3 cells. Correspondingly, the forced expression of NKX3.1 decreased IGF-1-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) and activation of the Elk-1 transcription factor and downregulated the expression of the downstream target genes c-fos and cyclin D1. Furthermore, the forced expression of NKX3.1 inhibited IGF-1-induced cell growth. In conclusion, NKX3.1 could downregulate IGF-1R expression and could inhibit IGF-1R-mediated mitogen-activated protein kinase (MAPK)/ERK and AKT signalling pathways, which might partially leads to the inhibition of IGF-1-induced cell growth. This study provides new insights into the molecular mechanisms that NKX3.1 exerts against prostate cancer and ultimately expands the scope of alternative approaches in advanced prostate cancer therapy.Asian Journal of Andrology advance online publication, 19 December 2011; doi:10.1038/aja.2011.158.

OBJECTIVE: Femoral neck geometric parameters (FNGPs), such as periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are highly genetically correlated with body lean mass. However, the specific SNPs/genes shared by these phenotypes are largely unknown. METHODS: To identify the specific SNPs/genes shared between FNGPs and appendicular lean mass (ALM), we performed an initial bivariate genome-wide association study (GWAS) by scanning ∼690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) and a follow-up replicate study in 2,286 unrelated US Caucasians. RESULTS: We identified 13 interesting SNPs that may be important for both FNGPs and ALM. Two SNPs, rs681900 located in the HK2 (hexokinase 2) gene and rs11859916 in the UMOD (uromodulin) gene, were bivariately associated with FNGPs and ALM (p = 7.58×10(-6) for ALM-BR and p = 2.93×10(-6) for ALM-W, respectively). The associations were then replicated in Caucasians, with corresponding p values of 0.024 for rs681900 and 0.047 for rs11859916. Meta-analyses yielded combined p values of 3.05×10(-6) and 2.31×10(-6) for rs681900 and rs11859916, respectively. Our findings are consistent with previous biological studies that implicated HK2 and UMOD in both FNGPs and ALM. Our study also identified a group of 11 contiguous SNPs, which spanned a region of ∼130 kb, were bivariately associated with FNGPs and ALM, with p values ranging from 3.06×10(-7) to 4.60×10(-6) for ALM-BR. The region contained two neighboring miRNA coding genes, MIR873 (MicroRNA873) and MIR876 (MicroRNA876). CONCLUSION: Our study implicated HK2, UMOD, MIR873 and MIR876, as pleiotropic genes underlying variation of both FNGPs and ALM, thus suggesting their important functional roles in co-regulating both FNGPs and ALM.

The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)-targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18-21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation (n= 1), in-frame deletion (n= 2), and L858R missense mutation (n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed.

NKX3.1 is a prostate-specific homeobox gene related strongly to prostate development and prostate cancer. However, little is known about the mechanism for regulation of NKX3.1 in prostate cancer. With RT-PCR and western blot, we found that NKX3.1 expression was enhanced by over-expression of Sp1 at both the mRNA and protein levels in prostate cancer LNCaP cells. To identify the Sp1-elements in the promoter region of NKX3.1, a 521 bp-promoter of human NKX3.1 gene containing three possible Sp1-elements was cloned into the upstream of the luciferase reporter gene in pGL(3)-basic plasmid. With deletion mutation analysis, plasmid construction, EMSA and oligonucleotide decoy technique, two Sp1-elements which located between +29 to +43 and -60 to -46 of NKX3.1 gene were identified and proven to be functional elements. It will be important to further study on the functions and the regulatory mechanisms of Sp1 element in NKX3.1 gene expression.

American CI-340 portable photosynthesis system was applied to compare the response of the net photosyntheitc rate to the light and the CO2 in Schisandra chinensis form different region and growing situation. The result showed the sample plant from Liaoning had higher light compensate point, higher light saturation point, higher maximum Pn value and higher apparent quantum yield than the sample from Jilin, so it can adapt to the changes of the sunlight in a day better. The weak plant from Jilin had lower light compenstate point, higher light saturation point and higher net photosynthetic rate, so it had stronger availability on light. The stronger one was more sensitive to the weak light. The Jilin sample had higher CE and lower CO2 compensate point compared to that from Liaoning, but when the density of CO2 rised to 240 micromol/mol, the Pn of Schisandra chinensis in Liaoning became much higher than that of Jilin. Under the natural CO2 density condition, the plant from Liaoning had higher photosynthesis ability.

OBJECTIVE: To evaluate the value of dual time point 11C-choline PET-CT in differentiating malignant from benign lesions of mediastinum. METHODS: Thirty-five patients with mediastinal diseases, including 8 non-small cell lung cancer or highly suspected lung cancer patients with mediastinal lymphadenectasis, were subject to CT, dual time point PET-CT and videomediastionoscopy within four weeks. 11C-choline was used as PET tracers to visualize various masses. The imaging protocol included the first PET scanning 5-10 min after the-injection of 370 MBq 11C-choline and then a second PET scanning 25-30 min later. The PET data were evaluated using the standardized uptake value (SUV) and the difference between the two point (DeltaSUV). Then the results were analyzed in accordance with the pathologic data. RESULTS: Eleven of the 35 patients with mediastinal diseases were diagnosed as with sarcoidosis, 6 with tuberculosis, 5 with lymphoma, 11 with nodal metastasis (8 had their modes from the lung and the primary lesions of the other 3 failed to be identified), and 2 with lung cancer with reactive hyperplasia lymph node. The SUV of the delayed images of the 16 malignant lesions was 6.48 (3.0-11.2), higher than that of the early images [6.17 (3.2-9.8)] with a DeltaSUV of 0.31 (-0.4-1.4). The value of SUV of delayed images of the 19 benign lesions was 4.99 (2.2-9.3), lower than that of early images [5.11 (2.9-8.3)] with a DeltaSUV of -0.12 (-0.9-1.0). The DeltaSUV of the benign lesions was significantly lower than that of the malignant lesions (F = 1.939, P = 0.04). The accuracy rates of diagnosis of mediastinal masses of CT, first-time PET-CT, dual time point PET-CT, and videomediastinoscopy were 54.3%(19/35), 74.3%(26/35), 82.9%(29/35), and 100%(35/35) respectively. Conclusion With a high diagnostic yield, videomediastinoscopy remains the gold standard in differentiation of malignant and benign lesions located in the middle mediastinum. Dual time point PET-CT may improve the accuracy.

Aim: To elucidate effects and mechanisms of emodin in prostate cancer cells. Methods: Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation was assayed by agarose gel electrophoresis. Apoptosis rate and the expression of Fas and FasL were assayed by flow cytometric analysis. The mRNA expression levels of androgen receptor (AR), prostate-specific antigen (PSA), p53, p21, Bcl-2, Bax, caspase-3,-8,-9 and Fas were detected by RT-PCR, and the protein expression levels of AR, p53 and p21 were detected by Western blot analysis. Results: In contrast to PC-3, emodin caused a marked increase in apoptosis and a decrease in cell proliferation in LNCaP cells. The expression of AR and PSA was decreased and the expression of p53 and p21 was increased as the emodin concentrations were increased. In the same time, emodin induced apoptosis of LNCaP cells through the upregulation of caspase-3 and -9, as well as the increase of Bax /Bcl-2 ratio. However, it did not involve modulation of Fas or caspase-8 protein expression. Conclusion: In prostate cancer cell line, LNCaP, emodin inhibites the proliferation by AR and p53-p21 pathways, and induces apoptosis via the mitochondrial pathway.