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Translational medicine refers to translating basic research achievements into the clinical application for diagnosis and treatment. There are still many issues of gastric cancer to be solved in clinical diagnosis and treatment. We need to focus on clinical questions, by means of basic research and multidisciplinary intersection approach, to further improve the overall efficacy of gastric cancer. Based on Ruijin Hospital′s translational research experiences, in this paper, the authors describe the future direction in the field of translational research, such as the etiology and pathogenesis of gastric cancer, tumor markers for early diagnosis, prediction of recurrence and metastasis, classification criteria, evaluation of chemotherapy, tumor heterogeneity, targeted therapy, immunotherapy and research platform establishment. In addition, here we share our perspective of the research on serum biomarkers, specific antibodies and improvement of drug delivery for gastric cancer.
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Objective:To explore the quality of inventory samples of a biobank stored in a deep freezer from 0 to over 10 years in Shanghai Ruijin Hospital. Methods:We extracted 24 pairs of stocked gastric cancer samples between 2003 and 2014. We used 1%aga-rose gel electrophoresis to analyze DNA and RNA purity and integrity while adding the RNA integrity number (RIN) for precise analysis. Bicinchonininc acid (BCA) assay was used for protein concentration evaluation. Coomassie brilliant blue method was used for protein integrity assay. Results: The samples were divided into four groups according to cryopreservation period (9 years). No significant difference in DNA integrity was found between the groups (P>0.05);however, DNA degradation in normal gastric mucosa was faster than that in gastric cancer tissue (P=0.023). The RIN significantly declined when the storage period was 6 years or longer (P=0.018). No significant difference in protein concentration was observed between different groups. Using Coo-massie brilliant blue method, we found significant differences in preserved proteins with different molecular weights. Proteins with varying molecular weights were detected in the groups with the following cryopreservation periods:>9 years, a small number of low-molecular-weight (average 36.5 KD) proteins;6-8 years, medium-molecular-weight (average 65.63KD) proteins;3-5 years, high-molecu-lar-weight (average 127.5 KD) proteins;<2 years, high-molecular-weight (average 160 KD) proteins. Conclusion:Cryopreservation does not exert an obvious effect on DNA. If the cryopreservation period is more than 5 years, serious degradation of RNA should occur;like-wise, degradation of proteins with higher molecular weight should occur.
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Today, the comprehensive surgical treatment for gastrointestinal cancer is almost in the perfect stage. It is difficult to further improve the curative effect by surgery only. To improve the overall curative effect of gastrointestinal tumor, translational medicine research should be promoted in the fields of the early diagnosis, etiology and pathogenesis and comprehensive treatment. Researches of discovering the new tumor markers for early diagnosis of tumor, etiology and pathogenesis involve many aspects, including environmental factors, genetic susceptibility, variation and accumulation of genetics, and epigenetic changes, which should be transferred to new methods of treatment. This review summarizes the gastrointestinal tumor-associated hot topics in the field of basic research and its progress, and provides the clinical clues from their conversion.
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Humans , Biomarkers, Tumor , Gastrointestinal Neoplasms , Diagnosis , GeneticsABSTRACT
MicroRNA are endogenous non-coding small RNA composed of approximately 18 - 23 nucleotides, mainly participating in post-transcription gene regulation. More and more data show that miR-21 is over-expressed in many human cancer cells and it was involved in cell differentiation, proliferation and apoptosis, closely related to tumorigenesis and the development of carcinoma as oncogene. Here, we will make a review about miR-21' s target gene, biosynthesis and regulation and clinical significance in order to provide a valued data for the future study and clinical application.
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Gastric cancer is one of the most common malignant tumors. Traditional Chinese medicine (TCM) has been widely used in treatment of gastric cancer, but still lacking large sample controlled trial to evaluate its efficacy.
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Melanoma-associated antigen MAGE-A3 is expressed in various types of tumors,but not in normal cells except testis and placenta.MAGE-A3 can be presented by both HLA class I and HLA class II molecules after being processed into antigen peptide.MAGE-A3 has recently been widely used in the diagnosis and immunotherapy of tumors.This article reviews the applications of MAGE-A3 in the diagnosis and immunotherapy of tumors.
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Objective:To investigate the effect of combination of D-methionine and docetaxel on gastric cancer cells. Methods:First, seven gastric cancer cell lines were cultured with three different kinds of media (D-Met, L-Met and Met~ - ) for five days, and cell cycle was detected by flow cytometry. Second, gastric cancer cells were respectively cultured in L-Met, D-Met, and Met~ - media for 96 h, then docetaxel was added into 3 media. After 24 h, proliferation was measured by MTT method. Results:All gastric cancer cell lines were arrested in G_ 2 /M phase (P
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Objective To investigate the influence of CO_2-insufflation on the expression of some adhesion molecules.Methods With an artificial pneumoperitoneum model in vitro, SW1116 colon carcinoma cells were exposed to CO_2-insufflation at different pressure (6, 9, 12 and 15 mmHg) for 1 hour. Control groups were exposed to room air. E-cadherin, ICAM-1, E-selectin, CD44 and CD44v6 were measured 0, 12, 24, 48 and 72 hours after CO_2-insufflation using flowcytometry and the mRNA level of these adhesion molecules were detected by real-time PCR.Results In transcription level the expression of ICAM-1 and CD44v6 on SW1116 cell line increased significantly in 6mmHg CO_2-insufflation group, in 9mmHg and 12mmHg group, E-cadherin,CD44 and CD44v6 increased significantly, and when the pressure was 15mmHg, CD44v6 increased (P
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Objective To investigate the role of loss of heterozygosity (LOH) of SMAD2 and its relationship with clinicopathological parameters of primary gastric carcinoma. Methods Fifty cases of primary gastric carcinoma were monitored by polymerase chain reaction -single strand conformation polymorphism (PCR- SSCP) and silver staining to detect SMAD2 LOH. Results The incidence of LOH was 40.0%(22/45) at D18S450 and 33.3%(16/48)at D18S460 . LOH occurred in SMAD2 was 55.1%(27/49).The rate of SMAD2 LOH was 72.0% (18/25) in primary gastric carcinoma with lymph node metastasis , which was significantly higher than that in without lymph node metastasis (P
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Objective To investigate the effect of CO_2-insufflation on mRNA expression of adhesion molecules of colorectal cancer cell lines. Methods With an artificial pneumoperitoneum model in vitro, SW1116 human colon carcinoma cell lines were exposed to CO_2-insufflation of different pressure ( 6mmHg , 9mmHg, 12mmHg and 15mmHg) for 1 hour. The mRNA level of E-cadherin, ICAM-1, CD44 and CD44v6 were measured after 0, 12, 24, 48 and 72 hours by real-time RT-PCR. Control cell lines were exposed to room air. ResultsThe mRNA expression of E-cadherin, ICAM-1, CD44 and CD44v6 increased significantly at 0h～48h after the cells were exposed to the continuous CO_2-insufflation for 1 hour(P
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Objective: To investigate the amino acids metabolism of gastric cancer cells in D-methionine(D-Met) medium.Methods: Six gastric cancer cell lines were respectively cultured with L-methionine(L-Met),D-Met,or without methionine(Met-) medium.Amino acids profile of every culture medium was measured by HPLC after 5 days. Results: Methionine concentration of six cell lines in Met medium was significantly lower than that in L-Met or D-Met medium(P
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Objective:To study the expression of D-amino acid oxidase(DAO) in gastric cancer cells and gastric mucosa cells. Methods:The expression of DAO was detected in seven gastric cancer cell lines and a normal gastric mucosa cell line GES-1 by real-time quantitative PCR and in tumor tissues and normal gastric mucous tissues of 46 patients with gastric cancer by RT-PCR.The liver and kidney tissues of nude mouse acted as positive controls.Results:DAO was expressed in the liver and kidney tissues of nude mouse,and DAO expression in kidney tissue was higher than that in liver tissue.DAO was not detected in seven gastric cancer cell lines and the normal gastric mucosa cell line GES-1.Except one tumor tissue sample,DAO was not detected in other gastric cancer tissues and all normal mucosa tissues.Conclusion:DAO was not expressed in gastric cancer cells and gastric mucosa cells.The nutritional treatment of D-Met in place of L-Met could avoid the disadvantage of methionine starvation to important organs,such as liver and kidney.
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Objectives: To study the effect of D-methionine on gastric cancer and its mechanism. Methods: We used a medium with D-methionine to culture six gastric cancer cell lines. The medium with L-methionine acted as control to culture cells. The proliferation of cells was detected by MTT. Apoptotic rates and cell cycle were detected by FMC. Results: Absorbance of all cell lines was significantly lower than control (P0.05). KATO-Ⅲ cells stayed more in G 0 /G 1 phase (P
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Objective To explore the values of CT virtual gastroscopy (CTVG), three dimensional (3D) and axial imaging by multi slice spiral CT (MSCT) in the preoperative assessment of gastric carcinoma. Methods Fifty two patients with gastric carcinoma proven by means of biopsy underwent CTVG, 3D imaging using the surface shaded display (SSD) and Raysum, and axial imaging. MSCT was first performed after the ingestion of gas, and a second tri phase MSCT scan was performed after the ingestion of water. The results were compared with those of fibrous gastroscopy (FG) and surgical pathological findings. Results The detection rates of gastric lesions with CTVG, 3D and axial imaging by MSCT were 98.1%, 96.2%, and 96.2%, respectively. The accuracy of judging gross type of advanced gastric carcinoma using CTVG combined with 3D imaging, FG,and axial imaging was 92.5% , 82.5%, and 75.0%, respectively.Statistical difference existed in CTVG combined with 3D imaging and axial imaging (P
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Objective To observe the effect of STK15 gene silencing on the growth of gastric cancer cell line-MKN45 in vitro and vivo. Methods STK15 expression was inhibited by RNAi techenique, STK15 protein level was detected by Western blot, the ability of MKN45 invasion in vitro was assessed by cell migration and invasion assay, the change of cell cycle distribution was detected by flowcytometry, MKN45 proliferation was measured by MTT method, and MKN45 cells treated with STK15 siRNA were transplanted subcutanuously in nude mice and their tumorgenesis ability were observed. Results After treatment with STK15 siRNA, STK15 protein level decreased obviously. Compared with control group, STK15- group showed lower invasion ability in vitro [ mean A value: (182?27 ) vs. (308?38 ), P