Xiongying Miao

Optimization extraction of Ganoderma lucidum polysaccharides and its immunity and antioxidant activities.

Extraction of Ganoderma lucidum polysaccharides (GLP) was optimized by response surface method (RSM). By running the optimization program with design expert within the experimental range investigated, the following optimum values were obtained: extraction time 230 min; extraction temperature 95 °C, and extraction number 5. The predicted polysaccharides production was 1.45%. Results showed that GLP significantly reduced the levels of serum IL-6 and TNF-α levels and increased the levels of serum IL-2, IL-4 and IL-10 in GLP-treated rats compared to gastric cancer model rats. In addition, administration of Ganoderma lucidum polysaccharides to GLP-treated group of rats improved the levels of serum and gastric tissue SOD, CAT and GSH-Px toward the control values in a dose-dependent manner. These findings show that GLP can enhance immunity and antioxidant activities in gastric cancer rats.

High expression of vanilloid receptor-1 is associated with better prognosis of patients with hepatocellular carcinoma

The vanilloid receptor-1 (VR1) is a ligand-gated, nonselective cation channel expressed predominantly by sensory neurons, but is also involved in carcinogenesis. To elucidate its role in hepatocarcinogenesis, we analyzed the expression of VR1 receptor in tumor and nontumor tissues from human hepatocellular carcinoma (HCC) samples. In situ hybridization analysis showed overexpression of VR1 mRNAs in 9/15 (60.0%) noncancer and 6/15 (40.0%) HCC samples. Immunohistochemistry of 62 HCC samples showed the expression of VR1 increased from normal liver or chronic hepatitis to cirrhosis. Marked expression of VR1 was noted in the majority [31/38 (81.6%)] of cirrhotic liver samples. In HCC, high expression of VR1 was observed in 30/62 (48.4%) cases. Clinicopathologic evaluation indicated a significant correlation between VR1 expression and histopathologic differentiation (P=0.001). Univariate analysis indicated that disease-free survival was significantly better in HCC patients with high versus those with low VR1 expression levels (P= 0.021). Our results indicate that VR1 has anti-HCC progression effects and can be potentially used as a prognostic indicator of HCC. The results suggest the potential beneficiary effects of VR1 expression on the prognosis of patients with HCC.

Anatomic resection of segment VIII of liver for hepatocellular carcinoma in cirrhotic patients based on an intrahepatic Glissonian approach

BACKGROUND Isolated segmentectomy VIII is a technically demanding operative procedure and is reported only rarely. To our knowledge, no reports on anatomic segmentectomy based on an intrahepatic approach have been described. For cirrhotic patients with hepatocellular carcinoma (HCC) limited to segment VIII, this is a parenchyma-preserving hepatectomy that can be tolerated. METHODS Eighteen patients with HCC underwent anatomic segment VIII segmentectomy from January 2005 to January 2008 in our institution. The operative techniques, postoperative, and oncologic outcomes were reviewed. RESULTS Anatomic segmentectomy VIII was feasible with the technology described herein in all patients. The perioperative and oncologic outcomes were comparable with those of other similar hepatic resections. The median follow-up time was 28 months. The 3-year survival rate was 65%. CONCLUSION Although complex and technically demanding, an intrahepatic Glissonian approach for anatomic segmentectomy of segment VIII is an oncologically radical but parenchyma-sparing hepatic resection. In terms of preserving greater functioning liver parenchyma, it may be a safe and effective alternative to extensive hepatectomy.

Clinical significance of transient receptor potential vanilloid 2 expression in human hepatocellular carcinoma

Transient receptor potential vanilloid 2 (TRPV2), one of the members of TRP (transient receptor potential) superfamily of ion channels, has been suggested to contribute to pain associated with inflammation or neuropathy. To investigate its role in hepatocarcinogenesis, we examined the expression of TRPV2 in human hepatocellular carcinoma (HCC) samples and analyzed the association of TRPV2 expression with its clinical significance. TRPV2 expression in 55 HCC patients was examined by immunohistochemistry, and the correlation between TRPV2 levels and clinicopathologic parameters was analyzed. Thirteen paired HCC specimens and their nontumor counterparts were investigated by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively. Quantitative RT-PCR and Western blotting analysis revealed that expression of TRPV2 at both the mRNA and protein levels were increased in cirrhotic livers compared with chronic hepatitis, whereas that also occurred in moderately and well-differentiated tumors compared with that of poorly differentiated tumors. Immunohistochemistry of the 55 HCC samples showed that the expression of TRPV2 increased when going from normal liver or chronic hepatitis to cirrhosis. Increased TRPV2 expression was observed in tissues of liver cirrhosis (31/37, 83.8%). In HCC, increased expression of TRPV2 was identified in 16/55 (29%) cases. Clinicopathologic assessment suggested a significant association between TRPV2 expression and portal vein invasion and histopathologic differentiation (P = 0.036 and 0.001, respectively). Our data suggest that TRPV2 plays a role in human hepatocarcinogenesis and might be a prognostic marker of patients with HCC.

A possible connection between adhesion regulating molecule 1 overexpression and nuclear factor kappa B activity in hepatocarcinogenesis

Adhesion regulating molecule 1 (ADRM1), a 19S proteasome cap-associated protein, and nuclear factor kappa B (NF-κB), a protein transcription factor controlling DNA transcription, may play an important role in tumorigenesis. Overexpression of ADRM1 and activation of NF-κB are well-observed in hepatocellular carcinoma (HCC). However, little is known about whether both are functionally connected during hepatocarcinogenesis, and the mechanisms involved. In this study, using laboratory techniques including short hairpin RNA (shRNA)-mediated knockdown, immunohistochemistry (IHC), both semi-quantitative and real-time RT-PCR, western blotting, MTT assay, transwell assay, flow cytometry and electrophoretic mobility shift assay (EMSA), the expression of ADRM1, the effects of ADRM1 knockdown on NF-κB activity, as well as the biological behavior of HCC cells including proliferation, migration, invasion and apoptosis were investigated in the samples from HCC patients and HCC cell lines. We found that both mRNA and protein levels of ADRM1 were increased in HCC tissues and that this increase in ADRM1 expression was parallel to the metastatic potential of HCC cell lines. After ADRM1 knockdown in MHCC97-H cells, the expression of IκB-α was increased and the NF-κB activity was reduced. Furthermore, ADRM1 knockdown inhibited MHCC97-H cell proliferation and induced cell apoptosis, and the migration and invasion of MHCC97-H cells were significantly repressed. These results indicate that there is a clear functional connection between ADRM1 and NF-κB in hepatocarcinogenesis, despite the precise mechanisms through which the two work together still being unknown.

Methylation-induced downregulation and tumor suppressive role of microRNA-29b in gastric cancer through targeting LASP1

MicroRNAs (miRs) have been demonstrated to play promoting or tumor suppressive roles in various human cancers, but the regulatory mechanism of miR-29b underlying gastric cancer development and progression still remains largely unclear. In the present study, we found that miR-29b was significantly downregulated in gastric cancer tissues and cell lines. Low expression of miR-29b was significantly associated with DNA methylation, and treatment with DNA methyltransferase inhibitor 5-Aza-20-deoxycytidine upregulated miR-29b in gastric cancer cells. In addition, both reduced miR-29b expression and miR-29b methylation were associated with disease progression and poor prognosis in gastric cancer. Restoration of miR-29b caused a reduction in gastric cancer cell proliferation, migration, and invasion, and inhibited tumor growth in vivo. LASP1 was then identified as a target gene of miR-29b in gastric cancer cells. Moreover, upregulation of LASP1 was significantly associated with gastric cancer progression and poor prognosis. Knockdown of LASP1 also suppressed the proliferation, migration, and invasion of gastric cancer cells. Moreover, overexpression of LASP1 impaired the suppressive effects of miR-29b on the malignant phenotypes of gastric cancer cells, suggesting that miR-29b may inhibit gastric cancer growth and metastasis via targeting LASP1. According to these data, miR-29b may be used as a potential therapeutic candidate for gastric cancer.

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

Fisetin (3,3′,4′,7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein-coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF-β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.

Application of liver hanging maneuver in anterior approach for isolated complete liver caudate lobectomy

OBJECTIVE To explore the technique and effect of liver hanging maneuver in anterior approach for isolated complete liver caudate lobectomy. METHODS We recruited 17 patients with liver caudate lobe tumor (13 primary hepatocellular carcinoma, 3 cholangiocarcinoma and 1 liver metastasis from colorectal cancer). Isolated complete caudate lobectomy with liver hanging maneuver was performed in 17 patients. RESULTS All 17 patients were successfully received the above-mentioned operation. The operative time was 166-427 (211.5 ± 20.1) min and the intraoperative blood loss was 372-1 208 (472.7 ± 83.6) mL. There was no operative death. The survival rates of follow up for 1, 3 and 5 years were 76.5%, 52.9% and 23.5%, respectively. CONCLUSION Liver hanging maneuver for isolated complete resection of the caudate lobe is an ideal approach for liver neoplasms resection.

Expression of RAD51 and MAX in pancreatic cancer rats

OBJECTIVE To establish a model of pancreatic cancer induced by 7,12-dimethyl-benzathracene (DMBA) in SD rats, and to detect the expression levels of RAD51 and Myc-associated factor X (MAX) and their effect on carcinogenesis of rat pancreas. METHODS Ninety SD rats were randomly divided into 3 groups: a model group, an intervention group, and a control group. DMBA was directly implanted into the parenchyma of rat pancreas (the model group and the intervention group). Rats in the intervention group were treated with 1 mL trichostatin A (TSA) saline solution (1 mug/mL) via ip weekly. Rats within 3~5 months in the model group and the intervention group were executed and observed by macrograph and under microscope. Meanwhile, the rats in the control group were executed at 5th month. The EnVision(TM) immunohistochemistry to assay the expression levels of RAD51 and MAX was used in conventional paraffin-embedded sections from the above pancreatic specimens. RESULTS The incidence of pancreatic cancer in the model group within 3-5 months was 48.7% (18/37), including 17 ductal adenocarcinomas and 1 fibrosarcoma. The incidence of pancreatic cancer in the intervention group within 3-5 months was 33.3%(12/36), including 11 ductal adenocarcinomas and 1 fibrosarcoma. The maximal diameter of mass in the model group was significantly higher than that in the intervention group (P<0.05). No pathological changes were found in pancreas of the control group and other extra-pancreatic main organs of the model group and the intervention group (such as the liver, biliary tract, gastrointestine tract, kidney, and lung). The positive rate of RAD51 was significantly higher in ductal adenocarcinoma in the model group, the intervention group, and the model group +the intervention group than those in corresponding groups of non-cancerous pancreatic tissues (P<0.01), but the positive rate of MAX expression was opposite to RAD51 expression(P<0.01). The positive tissues of RAD51 expression and/or negative tissues of MAX expression in non-cancerous tissues showed atypical-hyperplasia of ductal epitheli. Pancreas of the control group showed the negative expression of RAD51 and positive expression of MAX. Two cases of fibrosarcoma showed the negative expression of RAD51 and MAX. CONCLUSION DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. The TSA might have an inhibitive effect on carcinogenesis and growth of rat pancreas. The over-expression of RAD51 and/or lose-expression might have important effect on carcinogenesis induced DMBA in rat pancreas.

Molecular mechanism of photodynamic therapy

Despite its more than 100-year history in experimental and clinical use, photodynamic therapy (PDT) is only starting to be appreciated for its full potential. PDT combines a photosensitizer and light in the presence of oxygen to treat cancer and other disorders. This paper reviews the molecular mechanism of PDT at the cellular level as well as in therapeutic settings in vivo. The availability of multiple photosensitizers with different structures and functional properties makes PDT an extremely versatile and, conversely, a challenging approach to cancer therapy. The advancing understanding of molecular pathways helps to design improved regimens. As most cancers are being treated with combined therapies, PDT is being integrated into rationally designed regimens that exploit molecular responses to PDT for improved efficacy.