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1.  S100P, a calcium-binding protein, is preferentially associated with the growth of polypoid tumors in colorectal cancer 
Colorectal cancer (CRC) is a genetically heterogeneous disease with distinct morphological patterns. It has been shown that polypoid and ulcerative CRC displays different genetic alterations. In the present study, we aimed to investigate genes with differential expression patterns between ulcerative and polypoid CRC. cDNA microarray analysis was performed to compare the gene expression profiles in samples of ulcerative and polypoid CRC with paired normal mucosa samples. Potential candidate genes were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemistry. The epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray analysis identified 11 upregulated and 14 downregulated genes which were differentially expressed in samples from both tumor types compared to the matched normal mucosa samples. Among these, S100P was the only upregulated gene preferentially associated with polypoid CRC (P=0.032). The samples of polypoid CRC displayed significantly higher S100P protein and mRNA expression levels than the samples of ulcerative CRC (P<0.05, respectively). Using semi-quantitative immunohistochemical analyses, S100P overexpression was found to be preferentially associated with polypoid CRC (24/30 vs. 14/40, P<0.001). The relative methylation level determined by MSP did not differ significantly between the samples of polypoid and ulcerative CRC (43.36 vs. 49.10%, P=0.168), indicating that promoter hypomethylation was not directly related to the upregulation of S100P mRNA. Our results demonstrate that the upregulation of S100P mRNA and protein expression is a predominant characteristic in polypoid CRC, whereas ulcerative CRC presents with a wide range of expression levels, indicating that S100P overexpression is not a key determinant in conferring invasion properties. The clinicopathological significance of S100P in CRC requires further investigation in well-controlled studies.
PMCID: PMC4314409  PMID: 25585623
colorectal cancer; polypoid; ulcerative; cDNA micro-array; S100P
2.  A Retrospective Review of the Prognostic Value of ALDH-1, Bmi-1 and Nanog Stem Cell Markers in Esophageal Squamous Cell Carcinoma 
PLoS ONE  2014;9(8):e105676.
Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p = 0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p = 0.001), Bmi-1 (p = 0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p = 0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.
PMCID: PMC4141830  PMID: 25148045
3.  Liver-Specific Expressions of HBx and src in the p53 Mutant Trigger Hepatocarcinogenesis in Zebrafish 
PLoS ONE  2013;8(10):e76951.
Hepatocarcinogenesis is a multistep process that starts from fatty liver and transitions to fibrosis and, finally, into cancer. Many etiological factors, including hepatitis B virus X antigen (HBx) and p53 mutations, have been implicated in hepatocarcinogenesis. However, potential synergistic effects between these two factors and the underlying mechanisms by which they promote hepatocarcinogenesis are still unclear. In this report, we show that the synergistic action of HBx and p53 mutation triggers progressive hepatocellular carcinoma (HCC) formation via src activation in zebrafish. Liver-specific expression of HBx in wild-type zebrafish caused steatosis, fibrosis and glycogen accumulation. However, the induction of tumorigenesis by HBx was only observed in p53 mutant fish and occurred in association with the up-regulation and activation of the src tyrosine kinase pathway. Furthermore, the overexpression of src in p53 mutant zebrafish also caused hyperplasia, HCC, and sarcomatoid HCC, which were accompanied by increased levels of the signaling proteins p-erk, p-akt, myc, jnk1 and vegf. Increased expression levels of lipogenic factors and the genes involved in lipid metabolism and glycogen storage were detected during the early stages of hepatocarcinogenesis in the HBx and src transgenic zebrafish. The up-regulation of genes involved in cell cycle regulation, tumor progression and other molecular hallmarks of human liver cancer were found at later stages in both HBx and src transgenic, p53 mutant zebrafish. Together, our study demonstrates that HBx and src overexpression induced hepatocarcinogenesis in p53 mutant zebrafish. This phenomenon mimics human HCC formation and provides potential in vivo platforms for drug screening for therapies for human liver cancer.
PMCID: PMC3793937  PMID: 24130815
4.  Gastric and colonic metastases from primary lung adenocarcinoma: A case report and review of the literature 
Oncology Letters  2012;4(3):517-520.
Lung cancer is one of the leading causes of cancer-related mortality worldwide. Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports have been published and the majority of described metastatic sites involved the small intestine. In the present study, we report the first case of primary lung adenocarcinoma with both gastric and colonic metastases. We also review the published literature of primary lung cancer with gastrointestinal metastasis.
PMCID: PMC3439000  PMID: 22970049
lung cancer; gastrointestinal metastasis
5.  Probiotic use in preventing postoperative infection in liver transplant patients 
Although liver transplantation has been widely practised, post-operative bacterial infection is still a frequent complication which contributed to an increased risk of fatality. There were studies on preoperative use of probiotics for liver transplant patients and acquired reduction in postoperative sepsis and wound infection, but the relevant clinical experience with pre- and probiotics is still limited.
This study is to assess fibre and probiotic use aimed at preventing bacterial sepsis and wound complications in patients undergoing liver transplantation.
Study methods
There were a total of sixty-seven adult patients scheduled for liver transplantation were included in a public teaching hospital. From January to December 2011, 34 continuous patients following liver transplantation were put on fibre + probiotics. In retrospectively, from January to December 2010, 33 continuous patients were collected as a control group and they were only received fibre post operation. The incidence of bacterial infections was compared in patients receiving either fibre and lactobacillus or fibre only. Statistical analysis was performed using SPSS 15. The t test, fisher’s and chi- square test was used to compare discrete variables.
In summary, in the analysis of 67 liver transplant recipients, 8.8% group A patients developed infections compared to 30.3% group B patients. The difference between groups A and B was statistically significant in both cases. In addition, the duration of antibiotic therapy was significantly shorter in the lactobacillus-group. Wound infection was the most frequent infections and enterococci the most frequently isolated bacteria. Fibre and lactobacilli were well tolerated in most cases. The operating time, amount of intra- and post-operatively transfused units of blood, fresh frozen plasma and albumin did not differ significantly between the groups.
Combined fibre and probiotics could lower the incidence of bacterial infections and shorten the duration of antibiotic therapy following liver transplantation in comparison to conventional nutrition. In contrast to antibiotics, it is relatively cheap and does not cause resistant strains or serious side effects.
PMCID: PMC3924667  PMID: 24570932
Liver transplantation; probiotics; bacterial infection
6.  Autophagy Suppresses RIP Kinase-Dependent Necrosis Enabling Survival to mTOR Inhibition 
PLoS ONE  2012;7(7):e41831.
mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC) cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs) and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of mitochondria is required for cell survival since mTOR inhibition turns off Nrf2 antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an imbalance between ROS production and defense, causing necroptosis that may enhance cancer treatment efficacy.
PMCID: PMC3406086  PMID: 22848625
7.  Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report 
Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.
PMCID: PMC3488575  PMID: 22776211
Brain metastasis; IPMN; Pancreatic cancer; Oncocytic IPMN
8.  De novo malignant solitary fibrous tumor of the kidney 
Diagnostic Pathology  2011;6:96.
The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki-67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease-free for 30 months, long-term follow-up is still mandatory.
PMCID: PMC3195699  PMID: 21970525
solitary fibrous tumor; kidney; malignant; de novo; dedifferentiation; CD34
9.  Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer 
Cancers  2010;3(1):61-78.
The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.
PMCID: PMC3756349  PMID: 24212606
nanoparticles; drug delivery system; monomethoxy poly(ethylene glycol); poly(ε-caprolactone); safety evaluation; biodistribution; antitumor activity

Results 1-9 (9)