科创中国

Dietary consumption of genistein, found in soy, has been associated with a potentially protective role in colorectal cancer (CRC) development and progression. Herein we demonstrate that genistein will inhibit human CRC cell invasion and migration, that it does so at non-cytotoxic concentrations and we demonstrate this in multiple human CRC cell lines. After orthotopic implantation of human CRC tumors into mice, oral genistein did not inhibit tumor growth, but did inhibit distant metastasis formation, and was non-toxic to mice. Using a qPCR array, we screened for genistein-induced changes in gene expression, followed by Western blot confirmation, demonstrating that genistein downregulated matrix metalloproteinase 2 and Fms- Related Tyrosine Kinase 4 (FLT4; vascular endothelial growth factor receptor 3). After demonstrating that genistein suppressed neo-angiogenesis in mouse tumors, we examined FLT4 expression in primary CRC and adjacent normal colonic tissue from 60 human subjects, demonstrating that increased FLT4 significantly correlates with increased stage and decreased survival. In summary, we demonstrate for the first time that genistein inhibits human CRC metastasis at dietary, non-toxic, doses. FLT4 is identified as a marker of metastatic disease, and as a response marker for small molecule therapeutics that inhibit CRC metastasis.

Xiao Xiao;Zhiguo Liu;Rui Wang;Jiayin Wang;Song Zhang;Xiqiang Cai;Kaichun Wu;Raymond C. Bergan;Li Xu;代明 樊

Oncotarget

2015

Phage display technology is now well established as an important experimental approach in designing new reagents for diagnosis of diseases and development of novel vaccines. Aiming at identifying possible immunogenic mimotopes of gastric cancer-associated antigen, we used a monoclonal antibody against gastric cancer, named monoclonal antibody MG7, to screen two phage-displayed nanopeptide libraries. All selected phages were used to immunize BALB/c mice separately. By immunohistochemical staining the tissue sections with the immunized mice sera, we identified one phage that induced gastric cancer-specific antibody response. Consistent with our reported results before, we demonstrate that specific immunogenic epitopes can be isolated by screening phage-displayed library even when natural antigens are not readily available.

Li Xu;Bo Quan Jin;代明 樊

Molecular Cancer Therapeutics

2003-3

Acute portal vein thrombosis (PVT) is rarely encountered by clinicians. The most common manifestation of acute PVT is sudden onset of abdominal pain. A computed tomography scan without contrast often shows a high-density material in the portal vein. After injection of contrast agents, absence of luminal enhancement and enlargement of the obstructed portal vein are shown. In this case report, we demonstrated a rare computed tomography finding in which the diameter of the main portal vein was enormously distended to 3-fold that of the aorta in a patient with recent PVT. Despite thrombolysis and anticoagulation were immediately given, portal venous recanalization was not achieved in the patient. After 5 years, variceal bleeding and ascites occurred and liver function had persistently deteriorated. Finally, he died of progressive liver failure. Considering this case, we suggest that an early decision for invasive interventional treatment might be necessary to both increase the rate of portal venous recanalization and improve prognosis, as anticoagulation and thrombolysis therapy failed to recanalize recent PVT.

Xingshun Qi;Guohong Han;Zhanxin Yin;Chuangye He;Ming Bai;Zhiping Yang;Wengang Guo;Jing Niu;Kaichun Wu;代明 樊

Case Reports in Gastroenterology

2011-1

Introduction: Drug resistance is a major clinical obstacle to the successful treatment of human cancer. The microRNAs-21 (miR-21), an oncomiR, may play an important role in the progress of drug resistance. Areas covered: This review covers all related literature on miR-21 in drug resistance of human cancers and analyzes the expression, biological functions and targets of it. This study also envisages future developments toward its clinical and therapeutic applications in cancer treatment. Expert opinion: The miR-21 may promote the drug resistance of various cancers. Inhibitors of miR-21 may function as effective approaches for reversing drug resistance in cancer cells. There is a tough way from discovering the function of miR-21 to clinical use. Further understanding of miR-21-mediated signaling pathways will help to promote the therapeutic-clinical use of miR-21 in cancer.

Liu Hong;Yu Han;Yujie Zhang;Hongwei Zhang;Qingchuan Zhao;Kaichun Wu;代明 樊

Expert Opinion on Therapeutic Targets

2013-9

Objective: Budd-Chiari syndrome (BCS) can be incidentally complicated by hepatocellular carcinoma (HCC), thereby decreasing the survival of these patients. Our study aims to systematically review the prevalence and risk factors of HCC in BCS patients. Methods: A PubMed search was performed to identify all original articles that reported the prevalence and risk factors of HCC in BCS patients. Primary items were the prevalence and risk factors of HCC in BCS patients. Results: Of 1487 articles identified, 16 were included in our study. The prevalence of HCC in BCS is 2.0-46.2% in 12 Asian studies, 40.0-51.6% in two African studies, 11.3% in one European study, and 11.1% in one American study. Irrespective of hepatitis as the underlying risk factor of HCC, the pooled prevalence of HCC was 17.6% in BCS patients [95% confidence interval (CI): 10.1-26.7%], 26.5% in inferior vena cava obstruction (95% CI: 14.4-40.7%), and 4.2% in hepatic vein obstruction (95% CI: 1.6-7.8%). As patients with HCC and concomitant hepatitis were excluded, the pooled prevalence of HCC was 15.4% in BCS patients (95% CI: 6.8-26.7%). Heterogeneity among studies was statistically significant in these meta-analyses. The risk factors of HCC in BCS included hepatic venous pressure gradient and female sex in two Asian studies, and male sex, factor V Leiden mutation, and inferior vena cava obstruction in one European study. Conclusion: HCC was frequent in BCS. However, there was a huge variation among studies. Routine surveillance for HCC is warranted in BCS patients. The risk factors of HCC in BCS may vary depending on the geographic origin of the studies.

Weirong Ren;Xingshun Qi;Zhiping Yang;Guohong Han;代明 樊

European Journal of Gastroenterology and Hepatology

2013-7

代明 樊

Zhonghua nei ke za zhi [Chinese journal of internal medicine]

2006-7

Objective: To examine the expression of heat shock protein (HSP) 90 β in human gastric cancer tissue and SGC7901/VCR of MDR-type gastric cancer cell line. Methods: Immunohistochemical staining and in situ hybridization methods. Results: Heat shock protein 90 β was mainly located in the cell cytoplasma and weakly expressed in non-cancerous gastric mucosa. The expression rates of HSP90 β in normal gastric mucosa, gastritis and para-cancer tissues were 11.76%, 13.04% and 11.42% respectively, and there were no significant differences between them (P > 0.05). The expression of HSP90 β was increased in gastric cancer. The positive rate of HSP90 β in gastric cancer tissue was 30.00%, and was higher than non-cancerous gastric mucosa (P < 0.05). The expression rates of HSP90 β in well differentiated, moderately differentiated, poorly differentiated gastric cancer and mucinous carcinoma were 15.38%, 31.25%, 33.33%, and 42.85% respectively. The expression of HSP90 β in SGC7901/ VCR of MDR-type gastric cell line was higher than in its parental cell line SGC7901. In situ hybridization showed that the positive signal of HSP90 β was mainly located in the cell cytoplasma. Conclusions: The expression of HSP90 β was higher in gastric cancer tissue than in non-cancerous gastric mucosa. In gastric cancer tissue, the expression of HSP90 β was greater in poorly differentiated cancer tissue, and in SGC7901/VCR of MDR-type gastric cancer cell line the expression of HSP90 β was higher than that in its parental cell line SGC7901.

Xianling Liu;Ling Ye;Jianbo Wang;代明 樊

Chinese Medical Journal

1999-12

Liu Hong;Kaichun Wu;代明 樊

Annals of Internal Medicine

2008-9-2

The aim of this study was to predict and characterize a novel HLA-A2-restricted T-cell epitope of the human heparanase (HPSE) protein, as well as to evaluate its antitumor immunological effects in vitro with an 8-branched multiple antigenic peptide (MAP) design. The amino acid sequence of HPSE was scanned, and the cytotoxic T lymphocyte (CTL) epitopes were predicted using HLA-A2-restricted epitope-predictive algorithms based on supermotif and quantitative motif methods. The affinity of candidate peptides to HLA-A2 was evaluated using peptide-binding assay, by virtue of the characteristics of T2 cells. The MAPs consisting of the selected peptides were synthesized using an 8-branched design. The specific CTL-inducing ability of the MAPs was assessed by LDH release assay, and the CTL activity was evaluated by INF-γ ELISPOT assay. Among the predicted nonapeptides, the FLNPDVLDI peptide of HPSE showed the highest affinity to the HLA-A2 molecule. The 8-branched MAP comprising FLNPDVLDI induced specific CTLs for human HPSE in vitro, which effectively secreted IFN-γ and potently lysed HCC97-H human hepatocarcinoma cells and SW-480 human colonic carcinoma cells. The nonapeptide FLNPDVLDI of human HPSE appears to be a novel HLA-A2-restricted CTL epitope, and its 8-branch designed MAP is capable of inducing a potent HPSE-specific CTL response against tumor cells in vitro. Our study provides theoretical evidence for the peptide-based antitumor immunotherapy.

Jun Zhang;Jianmin Yang;代明 樊;Houquan Tao;Huiju Wang;Tong Yu

Oncology Reports

2013-5

Upregulated gene 4 (URG4), a novel gene located on 7 chromosome (7p13), was found to contribute to hepatocarcinogenesis. However, the role of URG4 in the gastric carcinogenesis still remains unclear. In the present study, URG4 was found by immunohistochemistry to be upregulated in human gastric cancer tissues compared with matched adjacent nonneoplastic tissues. The proliferating cell nuclear antigen index is higher in gastric cancer tissues with high URG4 expression than in those with low URG4 expression. The growth of GES-1 cells, which are immortalized human gastric epithelial mucosa cells with baseline URG4 expression, was accelerated by URG4 induction. Downregulation of URG4 through URG4 small interfering RNA (siRNA) in SGC7901 and MKN28 cells, which had high endogenous URG4 expression, suppressed cell proliferation in both of these cells. URG4-siRNA also inhibited the proliferation of SGC7901 and MKN28 cells in soft agar and tumor formation in nude mice. Overexpression of URG4 in GES cells upregulated cyclin D1, whereas repression of URG4 in SGC7901 and MKN28 cells downregulated cyclin D1. The data suggested that URG4 played an important role in the development of human gastric cancer by regulating the expression of cyclin D1 and might be used as a potential therapeutic target for gastric cancer.

Jiugang Song;Huahong Xie;Zhaorui Lian;Guitao Yang;Rui Du;Yulei Du;Xue Zou;Hai Feng Jin;Juan Gao;Jie Liu;代明 樊

Neoplasia

2006-12