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ABSTRACT: Hepatocellular carcinoma (HCC) is a serious public health issue, the incidence of which is considered to be closely related to tobacco smoking, alcohol consumption, hepatitis B virus (HBV) infection and family history. The DNA repair system is an important protective mechanism against the development of malignant cells induced by internal and external environmental factors. The aim of this study was to investigate the association of polymorphisms of XRCC1-194, XRCC1-280 and XPD-312 DNA repair genes and the risk of development of HCC in Han Chinese patients. A case-control design was used including 252 HCC inpatients and 250 healthy controls recruited and matched by age, gender, tobacco smoking, alcohol consumption, HBV infection and family history. XPD Asp312Asn, XRCC1 Arg194Trp and XRCC1 Arg280His genes were examined using a sequencing assay method. Distributions of the genotype frequency and odds ratio (OR) between the two groups were analyzed. The results demonstrated that there was no significant difference in the frequencies of XPD Asp312Asn, XRCC1 Arg194Trp and XRCC1 Arg280His in the HCC cases and the control group. In the stratified analysis of different allele genotypes, the frequency of the XRCC1-194 site genotype was not significantly different between the case and control group. The presence of the XRCC1 280His genotype was associated with a significantly increased risk of HCC under conditions of HBV infection and family history [OR (95% CI): 1.68 (1.08-2.60), 4.20 (1.34-13.20), respectively]. Similarly, the XPD 312Asn significantly increased the risk of HCC under conditions of alcohol consumption, tobacco smoking, HBV infection and family history [OR (95% CI): 1.67 (1.10-2.60), 1.87 (1.18-2.96), 1.96 (1.24-3.10), 3.40 (1.32-8.76), respectively]. In conclusion, tobacco smoking and alcohol consumption are high risk factors of HCC for the XPD 312Asn genotype; HBV infection and family history increase the risk of HCC for the genotypes XRCC1 280His and XPD 312Asn.
Experimental and therapeutic medicine 08/2012; 4(2):285-290.
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ABSTRACT: Structural maintenance of chromosome 4 (SMC4) is associated with tumorigenesis. The present study aimed at detecting SMC4 expression in primary liver cancer and its association with clinicopathological patient data. A total of 72 primary liver cancer tissues and 6 liver cell lines were assessed for expression of SMC4 mRNA and protein with qRT-PCR, western blotting and immunohistochemistry, respectively. SMC4 siRNAs were constructed to knockdown SMC4 expression, and phenotypic changes of hepatocellular carcinoma (HCC) cells were analyzed using flow cytometry and cell viability assays. The data showed that SMC4 mRNA and protein were highly expressed in HCC tissues compared to the normal tissues. Immunohistochemical analysis revealed that 52 of 72 (72.2%) paraffin-embedded primary liver cancer tissues displayed strong cytoplasmic staining of SMC4 protein, whereas only 6 (8.3%) normal liver tissues showed immunostaining of SMC4. Statistical analysis showed that SMC4 expression was significantly associated with tumor size, de-differentiation, advanced stages and vascular invasion of the primary liver cancers. Moreover, knockdown of SMC4 expression reduced HCC cell proliferation. These data demonstrated that expression of SMC4 protein may be useful for the early detection and prediction of primary liver cancer progression.
Oncology Reports 07/2012; 28(4):1263-8. · 1.84 Impact Factor
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ABSTRACT: The expression of transmembrane and ubiquitin-like domain containing 1 (Tmub1) is upregulated during liver regeneration, however, the function and underlying molecular mechanisms responsible for Tmub1 action remain to be determined. This study utilized BRL-3A rat liver cells for Tmub1 shRNA lentivirus infection and IL-6 stimulation. Semi-quantitative RT-PCR and western blot analysis were used to detect mRNA and protein expression levels, respectively. A [3H]thymidine incorporation assay was performed to assess changes in cell proliferation rates. Laser scanning confocal microscopy and immunoprecipitation-western blotting were used to assess the interaction between Tmub1 and calcium-modulating cyclophilin ligand (CAML) protein. The effect of Tmub1 on calcium ion influx into BRL-3A cells was measured by inverted fluorescence microscopy. The data showed that IL-6 treatment induced proliferation of rat hepatocytes and expression of Tmub1 mRNA and protein, while Tmub1 shRNA knocked down Tmub1 expression at both the mRNA and protein levels. Furthermore, compared to the negative control, Tmub1 shRNA-infected BRL-3A cells were highly proliferative with or without IL-6 stimulation. Tmub1 is colocalized with CAML in the hepatocellular cytoplasm, whereas knockdown of Tmub1 expression upregulated expression of CAML protein. Influx of Ca2+ into rat liver cells was also affected after Tmub1 knockdown. The data from the current study demonstrate that Tmub1 plays a negative role in IL-6-induced hepatocyte proliferation, and indicate that the interaction between Tmub1 and CAML may mediate the function of Tmub1 in hepatocytes.
International Journal of Molecular Medicine 03/2012; 29(6):1106-12. · 1.98 Impact Factor
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ABSTRACT: The purpose of this study was to investigate hepatic mitochondrial DNA (mtDNA) damage and changes in its encoded products in patients with alcoholic cirrhosis (AC) in order to understand disease pathogenesis. We enrolled 23 patients with AC, 26 alcoholics without cirrhosis, and 25 normal subjects in this study. Hepatic mtDNA deletions were positioned using a combination of long and accurate polymerase chain reaction (LA PCR) and gene sequencing. The mtDNA copy number was measured using real-time quantitative PCR. The expression of the mtDNA-encoded cytochrome c oxidase 2 (cox2) was detected by western blotting. A large deletion of bases located at positions 749-15486 was identified in hepatic mtDNA from AC patients. Moreover, the mtDNA copy number was significantly reduced (P<0.05), and its encoded product, cox2, was significantly downregulated (P<0.05). Collectively, our results suggest that specific deletions and reduced copy numbers of hepatic mtDNA in patients with AC is an important pathogenetic factor.
International journal of clinical and experimental medicine 01/2012; 5(3):245-50.
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ABSTRACT: A treatment method based on drainage via retroperitoneal laparoscopy was adopted for 15 severe acute pancreatitis (SAP) patients to investigate the feasibility of the method. Ten patients received only drainage via retroperitoneal laparoscopy, four patients received drainage via both retroperitoneal and preperitoneal laparoscopy, and one patient received drainage via conversion to laparotomy. Thirteen patients exhibited a good drainage effect and were successfully cured without any other surgical treatment. Two patients had encapsulated effusions or pancreatic pseudocysts after surgery, but were successfully cured after lavage and B ultrasound-guided percutaneous catheter drainage. SAP treatment via retroperitoneal laparoscopic drainage is an effective surgical method, resulting in minor injury.
Frontiers of medicine. 09/2011; 5(3):302-5.
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Gastroenterology 01/2011; 140(1):e9-10. · 11.68 Impact Factor
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ABSTRACT: To investigate the effects of subtotal gastrectomy and Roux-en-Y gastrojejunostomy on the clinical outcome of patients with type 2 diabetes mellitus (T2DM).
We performed retrospective analysis of 21 patients with T2DM operated due to stomach cancer and upper gastrointestinal tract ulcer between January 2001 and June 2008.
The body mass index (BMl) of all patients was <30 kg/m(2). The mean postoperative follow-up period was 26.6 mo (range, 6 mo-5 y). Subtotal gastrectomy and Roux-en-Y gastrojejunostomy remarkably lowered the levels of fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPG), and glycated hemoglobin (HbA1c). Overall, 12 patients (57.1%) achieved adequate glycemic control (HbA1c < 7%) without antidiabetic medication and five patients (23.8%) showed good improvement. The total effectiveness rate of the surgery in T2DM patients was 81.0%.
Subtotal gastrectomy and Roux-en-Y gastrojejunostomy appear to be effective treatment modalities for controlling T2DM in patients with BMl <30 kg/m(2). However, more studies with long follow-up period and large number of patients are necessary to clarify the benefits of this procedure.
Journal of Surgical Research 11/2010; 164(1):e67-71. · 2.25 Impact Factor
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ABSTRACT: The biliary leakage is a common and even lethal postoperative complication to the patients after hepatectomy. However, we found that the patients who underwent this lethal postoperative complication could potentially acquire a faster restoration of remnant liver volume comparing with those without postoperative biliary leakage. We surmise that inflammatory response induced by biliary leakage after partial hepatectomy may be the one of reasons for this phenomenon. Abnormal levels of TNF-alpha, IL-6, and STAT3 caused by biliary leakage may be a main reason for fast liver regeneration. On the other hand, we hypothesize that biliary leakage may promote liver regeneration by activating the immune system after partial hepatectomy. Our hypothesis might provide a novel therapeutic strategy for patients who underwent liver failure after partial hepatectomy. For instance, the exogenous infection or controlling biliary leakage may be reasonable and deserve further study. With the aid of animal model of postoperative biliary leakage or intraabdominal bacterial infections, this hypothesis could be partially or fully confirmed.
Medical Hypotheses 08/2009; 73(6):925-6. · 1.39 Impact Factor
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ABSTRACT: The pancreatic leakage is a lethal postoperative complication to the patients after duodenopancreatectomy for carcinoma of head of pancreas. However, we found that the patients who survived this lethal postoperative complication could potentially acquire a longer survival time comparing with those without postoperative pancreatic leakage. We surmise pancreatic enzyme can destroy tumor cell directly by its strong corrosive action. On the other hand, pancreatic leakage can lead to severe bacterial infection which cause serial inflammatory reaction and immunological reaction. We hypothesize that celiac infection after pancreatic leakage might prevent cancer cellstransfuse to liver along duodenohepatic ligament. Our hypothesis might provide a novel therapeutic strategy for patients who underwent radical duodenopancreatectomy. For instance, the exogenous infection or controlling pancreatic leakage may be reasonable and deserve further study. With the aid of animal model of carcinoma of head of pancreas, this hypothesis could be partially or fully confirmed.
Medical Hypotheses 05/2009; 73(2):187-8. · 1.39 Impact Factor
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ABSTRACT: Various sensor-based immunoassay methods have been extensively developed for the detection of cancer antigen 15-3 (CA 15-3), but most often exhibit low detection signals and low detection sensitivity, and are unsuitable for routine use. The aim of this work is to develop a simple and sensitive electrochemical immunoassay for CA 15-3 in human serum by using nanogold and DNA-modified immunosensors. Prussian blue (PB), as a good mediator, was initially electrodeposited on a gold electrode surface, then double-layer nanogold particles and double-strand DNA (dsDNA) with the sandwich-type architecture were constructed on the PB-modified surface in turn, and then anti-CA 15-3 antibodies were adsorbed onto the surface of nanogold particles. The double-layer nanogold particles provided a good microenvironment for the immobilization of biomolecules. The presence of dsDNA enhanced the surface coverage of protein, and improved the sensitivity of the immunosensor. The performance and factors influencing the performance of the immunosensor were evaluated. Under optimal conditions, the proposed immunosensor exhibited a wide linear range from 1.0 to 240 ng/mL with a relatively low detection limit of 0.6 ng/mL (S/N=3) towards CA 15-3. The stability, reproducibility and precision of the as-prepared immunosensor were acceptable. 57 serum specimens were assayed by the developed immunosensor and standard enzyme-linked immunosorbent assay (ELISA), respectively, and the results obtained were almost consistent. More importantly, the proposed methodology could be further developed for the immobilization of other proteins and biocompounds.
Electroanalysis 11/2008; 20(24):2621 - 2628. · 2.87 Impact Factor
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ABSTRACT: A new conductometric immunoassay for hepatitis B surface antigen (HBsAg) was developed based bioelectrocatalytic reaction on a microcomb-type electrode by using double-codified nanogold particles as labels. This microcomb-type electrode was fabricated on an interdigitated transducer covered with a well-ordered anti-HBs/protein A/nanogold architecture. The double-codified nanogold particles were prepared by using nanogold-labeled anti-HBs antibodies conjugated with horseradish peroxidase (HRP). Sandwich-type immunoassay protocol was successfully introduced for the detection of HBsAg. The formation of the immunocomplex changed the direct electrical communication between the carried HRP and the electrode, and thus local conductivity variations could be assayed based on the bioelectrocatalytic reaction of the carried HRP in 0.01 M PBS (pH 7.0) containing 60 μM H2O2, 0.08 M KI and 0.1 M NaCl. Under optimized conditions, the linear range obtained by using HRP-conjugated anti-HBs as secondary antibodies was 1.5–450 ng/mL HBsAg, while the assay sensitivity by using double-codified nanogold particles could be further increased to 0.01 ng/mL with the linear range from 0.1 to 600 ng/mL HBsAg. The developed immunoassay method showed good precision, high sensitivity, acceptable stability and reproducibility, and could be used for the detection of real sample with consistent results in comparison with those obtained by the ELISA method.
Biochemical Engineering Journal.
