Publications by authors named "Wei-qun Lu"

16 Publications

  • Page 1 of 1

Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells.

Oncotarget 2017 Jul;8(27):44171-44185

Department of Nuclear Medicine, Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, P.R. China.

Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines. The abilities of cell formation, kinetics, migration, invasion, survival and apoptosis, as well as permeability glycoprotein (Pgp) expression were inspected before and after knocking-down PKM2/GLS1 expression. In addition, the influence of knocking-down PKM2/GLS1 expression was evaluated in vivo. Differentiated PKM2 and GLS1 expression in both THC8307 and THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1 can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors, reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken together, the present findings enriched our knowledge by demonstrating a significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We further propose that knockdown of PKM2/GLS1 expression may constitute a novel therapeutic strategy toward effective treatment for CRC.
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http://dx.doi.org/10.18632/oncotarget.17396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546471PMC
July 2017

Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis.

Oncotarget 2016 Dec;7(51):84695-84704

Department of Gastrointestinal Tumor Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.

The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67-2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43-1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08-2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01-2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03-4.65) and 49% (95% CI: 1.01-6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.
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http://dx.doi.org/10.18632/oncotarget.13218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356692PMC
December 2016

[Influence of oxaliplatin combined with LCP on proliferation and apoptosis of colon cancer cell line HT29].

Zhonghua Wei Chang Wai Ke Za Zhi 2013 Jan;16(1):84-8

Department of Gastrointestinal Surgery, Guangzhou Medical College, Guangzhou, China.

Objective: To study the effects of oxaliplatin combined with low-molecular-weight citrus pectin (LCP) on cell proliferation and apoptosis in human colon carcinoma cell line HT29 in vitro.

Methods: Effects of oxaliplatin alone and oxaliplatin combined with LCP on HT29 cells proliferation were determined by MTT. Coefficient of drug interaction (CDI) was calculated. Influence of oxaliplatin alone and oxaliplatin combined with LCP on HT29 cell apoptosis was determined by fluorescence activated cell sorting (FACS). Protein expression change of procaspase-3, 8, 9, PARP was examined by Western blotting.

Results: Both oxaliplatin alone and oxaliplatin combined with LCP could suppress HT29 cell proliferation in both dose- and time-dependent manner. The inhibitory effect of oxaliplatin combined with LCP on HT29 cell proliferation was more significant (P<0.01) with a CDI less than 1. FACS analysis showed that oxaliplatin alone and combination therapy could increase the apoptosis proportion of HT29 cells. After the drug treatment for 6, 24, and 48 hours, the apoptosis rate of oxaliplatin alone group was (9.76±0.47)%, (20.45±0.74)%, (28.70±3.29)%, and apoptotic rate of the combination group was (20.63±0.69)%, (34.35±1.02)%, (49.47±3.04)%, respectively, which was significantly higher as compared to oxaliplatin alone (P<0.01). Both oxaliplatin alone and combination therapy down-regulated expressions of procaspase-3, 9, and PARP protein. Procaspase-3, 9, PARP protein expression in combination group decreased more significantly, while procaspase-8 expression was not significantly different between the two groups.

Conclusion: LCP can enhance the ability of oxaliplatin to inhibit cell proliferation and induce apoptosis, which may be associated with the activation of mitochondrial apoptosis pathway.
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January 2013

[Hepatectomy combined with cryoablation and ethanol injection for unresectable multiple liver metastases from colorectal cancer].

Zhonghua Wei Chang Wai Ke Za Zhi 2012 Apr;15(4):370-2

Department of Gastrointestinal Oncological Surgery, Guangzhou Medical College, Guangzhou, China.

Objective: To evaluate the efficacy and safety of hepatectomy combined with cryoablation and ethanol injection in patients with unresectable multiple liver metastases from colorectal cancer.

Methods: Clinical data of 23 patients with multiple liver metastases form colorectal cancer in the Affiliated Tumor Hospital of Guangzhou Medical College between January 2005 and December 2010 were analyzed retrospectively. There were 15 males and 8 females with average age of 52.2 years. All the patients underwent hepatectomy combined with ultrasound-guided cryoablation and ethanol injection intraoperatively.

Results: Among 98 lesions in 23 patients, 45 were removed intraoperatively and 53 were treated by cryoablation and ethanol injection. Operative time for liver lesions ranged from 27 to 96 minutes and intraoperative blood loss 50 to 450 ml. One patient developed pleural effusion and 1 myoglobinuria after operation. All the patients were followed up with a median follow-up time of 34 months(8 to 70 months). The 1-, 3-, and 5-year survival rates were 83.2%, 45.5% and 37.6% respectively.

Conclusion: Hepatectomy combined with cryoablation and ethanol injection is an effective and safe treatment option for patients with unresectable multiple liver metastases from colorectal cancer.
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April 2012

Lithium impacts on the amplitude and period of the molecular circadian clockwork.

PLoS One 2012 12;7(3):e33292. Epub 2012 Mar 12.

Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.

Lithium salt has been widely used in treatment of Bipolar Disorder, a mental disturbance associated with circadian rhythm disruptions. Lithium mildly but consistently lengthens circadian period of behavioural rhythms in multiple organisms. To systematically address the impacts of lithium on circadian pacemaking and the underlying mechanisms, we measured locomotor activity in mice in vivo following chronic lithium treatment, and also tracked clock protein dynamics (PER2::Luciferase) in vitro in lithium-treated tissue slices/cells. Lithium lengthens period of both the locomotor activity rhythms, as well as the molecular oscillations in the suprachiasmatic nucleus, lung tissues and fibroblast cells. In addition, we also identified significantly elevated PER2::LUC expression and oscillation amplitude in both central and peripheral pacemakers. Elevation of PER2::LUC by lithium was not associated with changes in protein stabilities of PER2, but instead with increased transcription of Per2 gene. Although lithium and GSK3 inhibition showed opposing effects on clock period, they acted in a similar fashion to up-regulate PER2 expression and oscillation amplitude. Collectively, our data have identified a novel amplitude-enhancing effect of lithium on the PER2 protein rhythms in the central and peripheral circadian clockwork, which may involve a GSK3-mediated signalling pathway. These findings may advance our understanding of the therapeutic actions of lithium in Bipolar Disorder or other psychiatric diseases that involve circadian rhythm disruptions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033292PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299767PMC
August 2012

Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes.

Proc Natl Acad Sci U S A 2010 Aug 9;107(34):15240-5. Epub 2010 Aug 9.

Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.

Circadian pacemaking requires the orderly synthesis, posttranslational modification, and degradation of clock proteins. In mammals, mutations in casein kinase 1 (CK1) epsilon or delta can alter the circadian period, but the particular functions of the WT isoforms within the pacemaker remain unclear. We selectively targeted WT CK1epsilon and CK1delta using pharmacological inhibitors (PF-4800567 and PF-670462, respectively) alongside genetic knockout and knockdown to reveal that CK1 activity is essential to molecular pacemaking. Moreover, CK1delta is the principal regulator of the clock period: pharmacological inhibition of CK1delta, but not CK1epsilon, significantly lengthened circadian rhythms in locomotor activity in vivo and molecular oscillations in the suprachiasmatic nucleus (SCN) and peripheral tissue slices in vitro. Period lengthening mediated by CK1delta inhibition was accompanied by nuclear retention of PER2 protein both in vitro and in vivo. Furthermore, phase mapping of the molecular clockwork in vitro showed that PF-670462 treatment lengthened the period in a phase-specific manner, selectively extending the duration of PER2-mediated transcriptional feedback. These findings suggested that CK1delta inhibition might be effective in increasing the amplitude and synchronization of disrupted circadian oscillators. This was tested using arrhythmic SCN slices derived from Vipr2(-/-) mice, in which PF-670462 treatment transiently restored robust circadian rhythms of PER2::Luc bioluminescence. Moreover, in mice rendered behaviorally arrhythmic by the Vipr2(-/-) mutation or by constant light, daily treatment with PF-670462 elicited robust 24-h activity cycles that persisted throughout treatment. Accordingly, selective pharmacological targeting of the endogenous circadian regulator CK1delta offers an avenue for therapeutic modulation of perturbed circadian behavior.
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http://dx.doi.org/10.1073/pnas.1005101107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930590PMC
August 2010

[Survey on the reproductive health status of married minority men at reproductive age in rural areas of Guizhou province].

Zhonghua Liu Xing Bing Xue Za Zhi 2008 Sep;29(9):951-2

Center for Research on Population, Guizhou University, Guiyang 550025, China.

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September 2008

Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model.

World J Gastroenterol 2008 Dec;14(48):7386-91

Department of Abdominal Surgery, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China.

Aim: To discuss the expression of glactin-3 in liver metastasis of colon cancer and its inhibition by modified citrus pectin (MCP) in mice.

Methods: Seventy-five Balb/c mice were randomly divided into negative control group (n = 15), positive control group (n = 15), low MCP concentration group (n = 15), middle MCP concentration group (n = 15) and high MCP concentration group (n = 15). CT26 colon cancer cells were injected into the subcapsule of mouse spleen in positive control group, low, middle and high MCP concentrations groups, except in negative control, to set up a colon cancer liver metastasis model. The concentration of MCP in drinking water was 0.0%, 0.0%, 1.0%, 2.5% and 5.0% (wt/vol), respectively. Liver metastasis of colon cancer was observed after 3 wk. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of galectin-3 in serum. Expression of galectin-3 in liver metastasis was detected by immunohistochemistry.

Results: Except for the negative group, the percentage of liver metastasis in the other 4 groups was 100%, 80%, 73.3% and 60%, respectively. The number of liver metastases in high MCP concentration group was significantly less than that in positive control group (P = 0.008). Except for the negative group, the median volume of implanted spleen tumor in the other 4 groups was 1.51 cm(3), 0.93 cm(3), 0.77 cm(3) and 0.70 cm(3), respectively. The volume of implanted tumor in middle and high MCP concentration groups was significantly smaller than that in positive control group (P = 0.019; P = 0.003). The concentration of serum galectin-3 in positive control and MCP treatment groups was significantly higher than that in the negative control group. However, there was no significant difference between them. Except for the negative control group, the expression of galectin-3 in liver metastases of the other 4 groups showed no significant difference.

Conclusion: Expression of galetin-3 increases significantly in liver metastasis of colon cancer, which can be effectively inhibited by MCP.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778124PMC
http://dx.doi.org/10.3748/wjg.14.7386DOI Listing
December 2008

Ligand modulation of REV-ERBalpha function resets the peripheral circadian clock in a phasic manner.

J Cell Sci 2008 Nov;121(Pt 21):3629-35

Faculty of Life Sciences, A. V. Hill Building, Oxford Road, Manchester M13 9PT, UK.

The nuclear receptor REV-ERBalpha is a key negative-feedback regulator of the biological clock. REV-ERBalpha binds to ROR elements of the Bmal1 (Arntl) promoter and represses Bmal1 transcription. This stabilizing negative loop is important for precise control of the circadian pacemaker. In the present study, we identified a novel synthetic REV-ERBalpha ligand, which enhances the recruitment of nuclear receptor co-repressor (NCoR) to REV-ERBalpha. In order to explore REV-ERBalpha action on resetting responses of the molecular clock, we first established the rhythmic transcription profile and expression level of REV-ERBalpha in Rat-1 fibroblasts. When applied at different phases of the circadian oscillation to cell models containing stably transfected Bmal1::Luc or Per2::Luc, the REV-ERBalpha ligand induced phase-dependent bi-directional phase shifts. When the phase changes were plotted against time, a clear phase response curve was revealed, with a significant peak-to-trough amplitude of ca. 5 hours. The phase-resetting effect was also observed when the compound was applied to primary lung fibroblasts and ectopic lung slices from transgenic PER2::Luc mice. Therefore, similar regulation of REV-ERBalpha function by endogenous ligands, such as heme, is likely to be an important mechanism for clock resetting. In addition, we identify a new means to generate phasic shifts in the clock.
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http://dx.doi.org/10.1242/jcs.035048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069549PMC
November 2008

Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma.

BMC Cancer 2006 May 2;6:110. Epub 2006 May 2.

Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China.

Background: Angiogenesis is one of the mechanisms most critical to the postoperative recurrence and metastasis of hepatocellular carcinoma (HCC). Thus, finding the molecular markers associated with angiogenesis may help identify patients at increased risk for recurrence and metastasis of HCC. This study was designed to investigate whether CD105 or CD34 could serve as a valid prognostic marker in patients with HCC by determining if there is a correlation between CD105 or CD34 expression and postoperative recurrence or metastasis.

Methods: Immunohistochemical staining for the CD105, CD34 and vascular endothelial growth factor (VEGF) antibodies was performed in 113 HCC tissue specimens containing paracarcinomatous tissue and in 14 normal liver tissue specimens. The quantitation of microvessels identified by anti-CD105 and anti-CD34 monoclonal antibodies and the semiquantitation of VEGF expression identified by anti-VEGF monoclonal antibody were analyzed in conjunction with the clinicopathological characteristics of the HCC and any available follow-up information about the patients from whom the specimens were obtained.

Results: CD105 was not expressed in the vascular endothelial cells of any normal liver tissue or paracarcinomatous liver tissue but was expressed in the vascular endothelial cells of all HCC tissue. In contrast, CD34 was expressed in the vascular endothelial cells of normal liver tissue, paracarcinomatous tissue, and HCC tissue in the following proportions of specimens: 86.7%, 93.8%, and 100%, respectively. The microvascular densities (MVDs) of HCC determined by using an anti-CD105 mAb (CD105-MVD) and an anti-CD34 mAb (CD34-MVD), were 71.7 +/- 8.3 (SD) and 106.3 +/- 10.4 (SD), respectively. There was a significant correlation between CD105-MVD and CD34-MVD (r = 0.248, P = 0.021). Although CD34-MVD was significantly correlated with VEGF expression (r = 0.243, P = 0.024), CD105-MVD was more closely correlated (r = 0.300, P= 0.005). The correlation between microscopic venous invasion and CD105-MVD, but not CD34-MVD, was also statistically significant (r = 0.254, P = 0.018). Univariate analysis showed that CD105-MVD was significantly correlated with the 2-year overall survival rate (P = 0.014); CD34-MVD was not (P = 0.601). Multivariate analysis confirmed that CD105-MVD was an independent prognostic factor and that CD34-MVD was not.

Conclusion: The anti-CD105 mAb is an ideal instrument to quantify new microvessels in HCC as compared with anti-CD34 mAb. CD105-MVD as compared with CD34-MVD is relevant a significant and independent prognostic indicator for recurrence and metastasis in HCC patients.
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http://dx.doi.org/10.1186/1471-2407-6-110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475877PMC
May 2006

Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in hepatocellular carcinoma: Impact on neovascularization and survival.

World J Gastroenterol 2005 Mar;11(11):1705-8

Department of General Surgery and Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Aim: To study the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival.

Methods: Expressions of HIF-1alpha, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1alpha and VEGF with the clinicopathological data and survival are analyzed.

Results: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1alpha in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1alpha in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1alpha as correlated with the expression of VEGF (r(s) = 0.459, P<0.01), but it also shows the expression of HIF-1alpha and VEGF as correlated with MVD (r(s) = 0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1alpha negative group and positive group are not significant (P>0.05).

Conclusion: HIF-1alpha plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305959PMC
http://dx.doi.org/10.3748/wjg.v11.i11.1705DOI Listing
March 2005

[Overexpression of the RhoC gene correlates with invasion and metastasis of hepatocellular carcinoma].

Zhonghua Zhong Liu Za Zhi 2004 May;26(5):279-82

Liver Cancer laboratory, Xiangya Hospital, Central South University, Changsha 410008, China.

Objective: Rho, a ras homologous gene, encodes a group of GTP-binding proteins. Our previous study suggested that one member of the Rho gene family, RhoC, was related to the progression of human hepatocellular carcinoma (HCC). This study is to elucidate correlation of Rho overexpression with invasion and metastasis of HCC.

Methods: The expression level of RhoC mRNA and protein in 25 cases of HCC and adjacent non-cancerous liver tissue was examined by RT-PCR and Western blot. Mutation of RhoC gene was examined by PCR-SSCP.

Results: The expression of RhoC mRNA and protein was found in all HCC and adjacent non-cancerous liver tissue. The expression level of RhoC mRNA and protein was significantly higher in tumor tissue than in adjacent non-cancerous liver tissue (1.8 +/- 1.1 vs 1.0 +/- 0.7; 33 992 +/- 10 384 vs 17 342 +/- 9998, P < 0.01). The degree of RhoC overexpression was even more marked in metastatic lesions than in primary tumors (P < 0.01). Overexpression of the rhoC gene was significantly correlated with such clinic-pathological findings as cell differentiation, portal vein invasion, number of primary tumor nodules and metastatic lesions (P < 0.05). Mutation of RhoC gene was found in none of the HCC specimens examined.

Conclusion: Overexpression of RhoC gene may play an important role in carcinogenesis and progression of HCC.
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May 2004

ADAM17 mRNA expression and pathological features of hepatocellular carcinoma.

World J Gastroenterol 2004 Sep;10(18):2735-9

Liver Cancer Laboratory, Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Aim: To study the expression of a disintegrin and metalloproteinase 17 (ADAM17) mRNA in hepatocellular carcinoma (HCC) and to evaluate the relationship between ADAM17 mRNA expression and clinicopathological features of HCC.

Methods: Hepatocellular carcinomas (HCC) from 31 cases were divided into small HCC (SHCC), nodular HCC (NHCC) and solitary large HCC (SLHCC) according to tumor diameter and the number of nodes. ADAM17 mRNA expressions were compared among those groups by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The relationship between ADAM17 mRNA expression level and clinicopathological features of HCC was evaluated.

Results: NHCC had lower differentiation and was more frequently of microvascular invasion (10/12) than SHCC (3/11) and SLHCC (3/8) (P<0.05), but no statistical difference was observed between SHCC and SLHCC comparing their clinicopathological features. ADAM17 mRNA expression was detected in 77.4% (24/31) of HCC tissues and was significantly higher than that in paired non-cancerous liver tissues in which only 35.5% (11/31) of the samples were detected of the expression (P<0.05). The expression of ADAM17 mRNA was much higher in NHCC than in SHCC and SLHCC (P<0.05), while no significant difference was discovered between SHCC and SLHCC. The quantities of ADAM17 mRNA were significantly higher in poorly differentiated HCC than in well or moderately differentiated HCC, but no statistical difference was found concerning liver cirrhosis, tumor capsule formation or microvascular invasion of the cancer.

Conclusion: The increased expression of ADAM17 may play a key role in the development of HCC. The expression levels of ADAM17 mRNA varied among different pathological types of HCC. Lower mRNA expression of ADAM17 mRNA in SLHCC may be associated with the better molecular pathological features of SLHCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572204PMC
http://dx.doi.org/10.3748/wjg.v10.i18.2735DOI Listing
September 2004

[Epidemiological study on semen quality of 562 volunteers aged 22-30].

Zhonghua Liu Xing Bing Xue Za Zhi 2004 Jan;25(1):44-8

Shanghai Medcal College, Fudan University, Shanghai 200032, China.

Objective: This study is to understand the difference of semen quality among the different areas and the related factors.

Methods: Five hundred and sixty-two people were under from seven provinces.

Results: Results showed that the quantity and density of semen, the rate of moving forward semen, livability, percent age of normal formed semen and the total number of semen were statistically different among the seven areas. The difference was ranged as 28.82%, with the highest 2.95 ml in Shanxi province and the lowest 2.29 ml in Henan province. Geometric mean of semen density was found the lowest 36.27 x 10(6)/ml in Guizhou province, next to it was 42.52 x 10(6)/ml in Shandong province and the highest was 74.77 x 10(6)/ml in Hebei province. The percent age with forward progression of semen was seen the lowest 44.40% in Henan province, followed by 51.88% in Hebei province and 52.88% in Zhejiang province and the highest were 76.50% in Shanghai, 75.24% in Shanxi province, with a range of 72.30%. The highest semen viability was 85.89% in Shanghai, while the lowest 72.35% in Henan, with a range of 18.71%. Normal sperm morphology was seen the lowest 68.45% in Hebei province, with the highest 88.06% in Guizhou province, and the range was 28.65%. The geometric mean of total sperm count was seen the highest 204.23 x 10(6)/ml in Hebei province and the lowest 77.69 x 10(6)/ml in Guizhou province. Results showed through analysis of variance that some indexes were different in some provinces.

Conclusion: The results indicated that the semen quality was different in different regions in China and its influential factors may be region and geography environment.
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January 2004

Effects of PI3K and p42/p44 MAPK on overexpression of vascular endothelial growth factor in hepatocellular carcinoma.

World J Gastroenterol 2004 Mar;10(6):809-12

Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Aim: To study the relationship between hypoxia or epidermal growth factor (EGF) and the overexpression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the signal transduction pathway of the transcription of VEGF in hepatoma cells.

Methods: Cobalt chloride and recombinant human EGF were used to stimulate the hepatoma cell lines HepG(2). VEGF mRNA was detected by using of semi-quantitative polymerase chain reaction (RT-PCR). Specific inhibitors of phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen activated protein kinase (MAPK) were used to observe the effects of the two kinases on the regulation of the transcription of VEGF in hepatoma cells.

Results: The expression of VEGF mRNA in HepG(2) cells cultured in serum-free medium was 0.117. However, 100 mumol/L cobalt chloride for 24 h increased the expression of VEGF mRNA and VEGF mRNA increased gradually with the increase of the concentration and duration of cobalt chloride. Also, 25 ng/mL recombinant human EGF stimulated the expression of VEGF in HepG(2) cells and the expression increased with the increase of EGF concentration. 5 mumol/L LY294002 inhibited the expression of VEGF stimulated by cobalt chloride or recombinant human EGF and the inhibition decreased step by step with increase of the concentration of LY294002. But even 20 mumol/L LY294002 could not completely block the expression of VEGF. In contrast, PD98059 had no inhibitory effects on the transcription of VEGF stimulated by cobalt chloride or recombinant human EGF.

Conclusion: The overexpression of VEGF in HCC could be promoted by hypoxia and EGF expression in HCC. The signal transduction pathway of VEGF transcription in HepG(2) cells may be through PI3K pathway, but not through p42/p44 MAPK pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727017PMC
http://dx.doi.org/10.3748/wjg.v10.i6.809DOI Listing
March 2004

Expression and significance of RhoC gene in hepatocellular carcinoma.

World J Gastroenterol 2003 Sep;9(9):1950-3

Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Aim: To investigate the expression of RhoC gene in hepatocellular carcinoma (HCC) and to evaluate the relationship between RhoC gene expression and invasion and metastasis of HCC.

Methods: mRNA expression level of RhoC gene was examined by reverse transcription-polymerase chain reaction (RT-PCR) in 25 cases of HCC and para-cancerous normal liver tissues. In addition, mutation of RhoC gene was examined by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP).

Results: The mRNA expression levels of RhoC in tumor tissues were significantly higher than those in para-cancerous normal liver tissues (1.8+/-1.1 vs 1.0+/-0.7, P<0.01). The metastatic lesions outside of liver also showed significantly higher RhoC mRNA levels than corresponding tumor tissues in liver (3.3+/-0.5 vs 2.0+/-0.7, P<0.01). There were significant associations between RhoC gene expression and certain clinical and pathological findings, including cell differentiation, vein invasion, number of tumor nodes and metastatic lesions. Mutation of RhoC gene was not found by PCR-SSCP.

Conclusion: The RhoC gene may be related to malignant transformation and development of HCC and may play an important role in the invasion and metastasis of HCC by overexpression but not mutation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656650PMC
http://dx.doi.org/10.3748/wjg.v9.i9.1950DOI Listing
September 2003
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