Underexpression of Deleted in liver cancer 2 (DLC2) is associated with overexpression of RhoA and poor prognosis in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>DLC2, a unique RhoGAP, has been recently identified as a tumor suppressor gene in hepatocellular carcinoma (HCC). However, the expression of DLC2 protein, and its relationship with RhoA in clinical hepatocellular carcinoma have not been studied. The aim of this study was to investigate the DLC2 protein expression and its correlation with expression of RhoA, as well as to evaluate the prognostic value of DLC2 for HCC patients.</p> <p>Methods</p> <p>Western blot and immunohistochemical staining were employed to detect DLC2 protein expression in 128 HCC specimens. The correlation between DLC2 protein expression and clinicopathologic outcome, and prognostic value of DLC2 for HCC patients were analyzed.</p> <p>Results</p> <p>HCC tissues revealed significantly lower level of DLC2 protein than pericarcinomatous liver tissues (PCLT). There was significant correlation between underexpression of DLC2 protein and cell differentiation. Meanwhile, underexpression of DLC2 protein was correlated with overexression of RhoA. Furthermore, HCC Patients with DLC2-negative expression showed a significantly poorer prognosis than those with DLC2-positve expression.</p> <p>Conclusion</p> <p>Our data strongly suggested that decreased DLC2 expression in HCC correlates with cell differentiation of HCC and overexpression of RhoA, underexpression of DLC2 is associated with poor prognosis in HCC patients.</p

Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis

<p>Abstract</p> <p>Background</p> <p>Interferon-α (IFN-α) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-α receptor (IFNAR). We investigated the role of IFNAR in RCC.</p> <p>Methods</p> <p>We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR), and IFNAR2 protein using Western blotting.</p> <p>Results</p> <p>The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N) for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/N ratio of IFNAR2 correlated with poor differentiation (<it>P </it>< 0.05), local invasion (<it>P </it>< 0.001), and metastasis (<it>P </it>< 0.0001). By multivariate analysis, a high T/N ratio of IFNAR2 predicted a shortened overall survival in all cases (<it>P </it>< 0.05) and a shorter disease-free survival in those without metastasis (M0; 68 cases, <it>P </it>< 0.05). Impressively, patients with a poorer response to IFN-α treatment had a higher IFNAR2 T/N ratio than those who had a good response (P < 0.05). IFNAR2c protein expression was higher in the primary tumors in patients with metastases (M1; 35 cases) compared to those without ( P < 0.0001).</p> <p>Conclusion</p> <p>IFNAR2 is associated with the progression of RCC.</p

Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC).</p> <p>Methods</p> <p>We measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction.</p> <p>Results</p> <p>The serum hepcidin-25 level was higher in patients with metastatic RCC than nonmetastatic RCC (<it>P </it>< 0.0001), and was positively correlated with the serum interleukin-6 and C-reactive protein levels (<it>P </it>< 0.001). Expression of hepcidin mRNA was lower in tumor tissues than in non-tumor tissues (<it>P </it>< 0.0001). The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue specimens from 32 patients. Hepcidin mRNA expression in tumor tissue was correlated with metastatic potential, but not with histological differentiation or tumor stage. Kaplan-Meier analysis showed that over expression of hepcidin mRNA was related to shorter overall survival in RCC patients. Univariate analysis (Cox proportional hazards model) showed that the hepcidin mRNA level was an independent prognostic factor for overall survival.</p> <p>Conclusion</p> <p>Our findings suggest that a high serum hepcidin-25 level may indicate the progression of RCC, and that upregulation of hepcidin mRNA expression in tumor tissue may be related to increased metastatic potential.</p

Single minimum incision endoscopic radical nephrectomy for renal tumors with preoperative virtual navigation using 3D-CT volume-rendering

<p>Abstract</p> <p>Background</p> <p>Single minimum incision endoscopic surgery (MIES) involves the use of a flexible high-definition laparoscope to facilitate open surgery. We reviewed our method of radical nephrectomy for renal tumors, which is single MIES combined with preoperative virtual surgery employing three-dimensional CT images reconstructed by the volume rendering method (3D-CT images) in order to safely and appropriately approach the renal hilar vessels. We also assessed the usefulness of 3D-CT images.</p> <p>Methods</p> <p>Radical nephrectomy was done by single MIES via the translumbar approach in 80 consecutive patients. We performed the initial 20 MIES nephrectomies without preoperative 3D-CT images and the subsequent 60 MIES nephrectomies with preoperative 3D-CT images for evaluation of the renal hilar vessels and the relation of each tumor to the surrounding structures. On the basis of the 3D information, preoperative virtual surgery was performed with a computer.</p> <p>Results</p> <p>Single MIES nephrectomy was successful in all patients. In the 60 patients who underwent 3D-CT, the number of renal arteries and veins corresponded exactly with the preoperative 3D-CT data (100% sensitivity and 100% specificity). These 60 nephrectomies were completed with a shorter operating time and smaller blood loss than the initial 20 nephrectomies.</p> <p>Conclusions</p> <p>Single MIES radical nephrectomy combined with 3D-CT and virtual surgery achieved a shorter operating time and less blood loss, possibly due to safer and easier handling of the renal hilar vessels.</p

Maize-soybean intercropping for sustainable intensification of cereal-legume cropping systems in northern Nigeria

Article purchased; Published online: 20 Nov 2017Field studies were conducted during the 2014 and 2015 wet seasons at Zaria in the northern Guinea savanna and at Iburu in the southern Guinea savanna of Nigeria to determine the productivity of maize– soybean intercropping system. There were four treatment combinations in the experiment: sole maize; sole soybean; maize spaced at 50 cm and intercropped with soybean; and maize spaced at 65 cm and intercropped with soybean. The experiment was laid out in a randomized complete block design with three replications. The results showed that sole cropped maize and soybean generally outperformed the intercropped component crops. Land Equivalent Ratio (LER) was greater than 1 for all the intercrop treatments, indicating that it is advantageous to grow maize and soybean in association than in pure stands. Except for 2014 in Zaria, LER for intercropped maize spaced at 50 cm was higher than that for maize spaced at 65 cm. Gross Monetary Value (GMV) was generally higher for intercrops than sole crops except in Iburu in 2015 where GMV for intercropped maize spaced at 65 cm was similar to those of sole maize and soybean. Monetary Advantage Index (MAI) was positive for all intercrop treatments in both locations and years, which shows definite yield and economic advantages compared to the sole cropping systems. This suggests that farmers can intercrop soybean and maize with maize spaced at 50 cm and 65 cm

ROCK1 and LIMK2 Interact in Spread but Not Blebbing Cancer Cells

Cancer cells migrating within a 3D microenvironment are able to adopt either a mesenchymal or amoeboid mode of migration. Amoeboid migration is characterised by membrane blebbing that is dependent on the Rho effectors, ROCK1/2. We identify LIMK2 as the preferred substrate for ROCK1 but find that LIMK2 did not induce membrane blebbing, suggesting that a LIMK2 pathway is not involved in amoeboid-mode migration. In support of this hypothesis, novel FRET data demonstrate a direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells. Our results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration

Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma

BackgroundThe purpose of this study was to identify new tumour suppressor microRNAs (miRs) in clear cell renal cell carcinoma (ccRCC), carry out functional analysis of their suppressive role and identify their specific target genes.MethodsTo explore suppressor miRs in RCC, miR microarray and real-time PCR were performed using HK-2 and A-498 cells. Cell viability, invasion and wound healing assays were carried out for functional analysis after miR transfection. To determine target genes of miR, we used messenger RNA (mRNA) microarray and target scan algorithms to identify target oncogenes. A 3'UTR luciferase assay was also performed. Protein expression of target genes in ccRCC tissues was confirmed by immunohistochemistry and was compared with miR-584 expression in ccRCC tissues.ResultsExpression of miR-584 in RCC (A-498 and 769-P) cells was downregulated compared with HK-2 cells. Transfection of miR-584 dramatically decreased cell motility. The ROCK-1 mRNA was inhibited by miR-584 and predicted to be target gene. The miR-584 decreased 3'UTR luciferase activity of ROCK-1 and ROCK-1 protein expression. Low expression of miR-584 in ccRCC tissues was correlated with high expression of ROCK-1 protein. The knockdown of ROCK-1 by siRNA inhibited cell motility.ConclusionmiR-584 is a new tumour suppressor miR in ccRCC and inhibits cell motility through downregulation of ROCK-1