The current status and important advances in multi-disciplinary treatment for advanced gastric cancer,including surgery,chemotherapy and radiotherapy,were reviewed in this article.An operative scheme based on the stage and biologic behavior of the tumor is adopted with the D_2 procedure combined with intraoperative peritoneal hyperthermic chemotherapy(IPHC) for stage Ⅱ and Ⅲ patients.Accurate preoperative staging is of utmost importance in making an appropriate therapeutic strategy.For patients with stage Ⅲ_B and Ⅳ gastric cancer,neo-adjuvant chemotherapy followed by cyto-reductive surgery,is helpful to prolong survival and improve the quality of life.Besides the 5-FU,cisplatin and doxorubicin based regimen,combination regimens employing newer generation cytotoxic agents including oxaliplatin,irinotecan,taxanes provided more promising efficacy.Postoperative chemo-radiotherapy is presently under investigation.

Lymphatic vessels are important for the spread of solid tumors, and recent researches indicated that lymphangiogenic factors(VEGF C and VEGF D)could stimulate lymphangiogenesis in tumors by activating their receptors on the lymphatic endothelial cells, then enhance the incidence of lymph node metastasis. In addition, inhibition of VEGFR 3 signaling could suppress tumor lymphangiogenesis and metastasis to lymph nodes, thus, inhibition of lymphangiogenesis can be expected to be a new method of blocking tumor metastasis.

Gastric cancer is one of the most common malignant gastrointestinal tumors with a high mortality in China. However, the pathogenesis of gastric cancer is not clear. Recently, with the development of cancer stem cell research, more and more studies have been focused on the gastric cancer stem cell. In this review, we will discuss the conception and the study status of the gastric cancer stem cells in addition to the treatment for the cancer stem cell.

Objective To investigate the relationship between the expression of p53 and vascular endothelial growth factor (VEGF) to angiogenesis in gastric carcinoma. Methods The expression of p53、VEGF and microvascular density (MVD) in gastric carcinoma was examined by immunohistochemical staining in 60 cases.Results There was a close correlation between MVD, p53 as well as VEGF expression and several clinicopathological factors including tumor size(P

Objective To investigate the effect of cytosine deaminase(CD)/ 5-FC system in inhibiting growth of LoVo colorectal carcinoma grated in nude mice.Method The retroviral vector pCD2 containing CD suicidal gene was packaged in PA317 cells,the supernatant of recombinant retrovirus was then injected into tumor sites.Result Obvious regression of the tumor occurred after serial intraperitoneal administration of the prodrug for the 5-FC.Conclusion CD gene can be a useful tatic in the comprehensive treatment of colorectal carcinomas.

University of Manchester who first introduced Problem based learning(PBL)to the UK medical education,and adopted this new curriculum in 1994.Notably,Cambridge and Oxford have always had a high proportion of student-centred and self-directed learning,and have therefore not introduced PBL.Other medical schools have followed the example of Manchester,now PBL has become the mainstream curriculum in British medical edacation.First,this article is going to introduce how PBL curriculum is structured at Manchester medical school,and then reflect and give some thoughts on its current practice.

AIM:To investigate the effect of adenovirus-medicated decorin gene transfer into rat mesangial cells(RMCs)on the expression of decorin,TGF-?1 and the extracellular matrix(ECM)components.METHODS:Rat mesangial cells were transfected with recombinant adenovirus vector of decorin,the levels of mRNA for decorin,TGF-?1,collagen type IV and fibronectin were estimated by semi-quantitative RT-PCR.RESULTS:The transfection of AD-DCN significantly increased decorin mRNA expression compared with negative control(P

Objective To investigate the effects of hypoxia on malignant phenotype of a hepatocellular carcinoma(HCC)cell line and its molecular basis.Methods Human HCC cell line with highly metastatic potential(MHCC97H)was grown under hypoxia(induced by 100 μmol/L CoCl_2)and normoxic conditions respectively.To observe the effects of hypoxia on MHCC97H cells was observed,the tumorigenicity was carried out by soft agar cloning method in vitro and inoculation in nude mice in vivo;Invasive and metastatic potential were measured.Experiments with and/or without Matrigel in vitro and a metastatic human HCC orthotopic nude mice model by HAL in vivo.To clarify the molecular background,the proliferation of cells were analyzed by MTT assay and the cell cycle was detected by flow cytometry;The expression of embryonic stem cell(ES)-like genes(Oct4,Nanog and Sox2)were detected by real-time RT-PCR;CD90~+ and CD133~+ subpopulation from MHCC97H cells were isolated by flow cytometry and the expressions of CD90 and CD133 of MHCC97H cells were analyzed by immunofluorescence.Results Hypoxia increased tumor migration(t=2.792,P=0.023),invasiveness(t=7.624,P＜0.0001)and clone forming ability(t=3.292,P=0.011)of MHCC97H cells in vitro,and promoted tumorigenesis(x~2=8.571,P=0.015)and pulmonary metastasis(x~2=5.507,P=0.031)in vivo.The proliferation of MHCC97H cells arrest under hypoxic conditions accompanied with increased proportion of cells in G1 phase,the expressions of Oct4,Nanog,Sox2 significantly increased in response to hypoxia,but the fluorescence intensity and number of CD90~+ and CD133~+ MHCC97H cells decreased or unchanged.Conclusion Hypoxia increases aggressiveness of MHCC97H cells,which was correlated with the acquisition of embryonic stem cell-like characteristics.

Objective To observe the toxicity and adverse reaction of interleukin(IL) 2 gene modified allogenic gastric cancer cell line in far advanced gastric cancer patients. Methods A phase Ⅰ clinical trial was conducted for sixteen far advanced gastric cancer patients with IL 2 gene modified gastric cancer cell line. By gene recombinant technique, human IL 2 cDNA was transfected into human gastric cancer cell line MKN45 via retrovirus based vector.These cells were then inactivated by irradiation (100 Gy) and were cryopreserved for the vaccine. The immunization were administrated subcutaneously at the first, 8 th , 15 th , 29 th and 58 th day. The patients were divided into 4 dosage groups, which the dosage of the vaccine was administrated in each subsequent level. The toxicity and adverse reaction were evaluated by WHO criteria. Results Fifteen of the 16 patients completed the immunization. Side effects of treatment consisted of mild to moderate fever, redness and swelling at the site of injection, which were the most common symptoms. Only one patient abandoned after the third injection due to rapidly progressive disease. Other reactions including allergic shock, bone marrow depression and disturbance of hepatorenal function were not observed during the immunization.In some patients, the serum transferrin, humoral immune parameters such as IgG, IgA, IgM,IL 2 and cellular immune parameters such as CD + 3,CD + 4,CD + 8 had been improved after treatment.Conclusions This trial demonstrates the feasibility, safety and potential therapeutic effects of vaccination of gastric cancer patients with allogenic, gene modified gastric cancer cell line. The dosage of the vaccine recommended for phase Ⅱ clinical trail is 5?10 7 cells per time.

Objectives:To study the methionine dependence(Met dependence) of human primary gastric cancer cells in vitro when Met in the culture medium was replaced by its precursor homocysteine(Hcy),and the effect of methionine starvation in combination with chemotherapeutical agents on gastric cancer cells. Methods:Fresh and sterile gastric cancer samples were managed to single cell suspensions and then were cultured in Met -Hcy + and Met +Hcy - medium separately,the proliferation of tumor cells in different culture media was examined by microcytotoxicity(MTT) assay.Meanwhile,the inhibition rate of tumor cells by ADM、DDP、5 FU、MMC and MTX in Met -Hcy +medium was separately tested. Results:①In Met -Hcy + medium,the human primary gastric cancer cell decreased;②Methionine deprivation in combination with chemotherapy enhanced obviously the killing capacity of each chemotherapeutical agent. Conclusions:①Human primary gastric cancer cells in vitro appears Met dependent.②The combined application of Met -Hcy + medium and different chemotherapeutical agents could enhance the antitumor effect of chemotherapy on primary gastric cancer cells.③MTT assay was an efficient way to examine the sensititivity of methionine starvation therapy combined with individualized chemotherapeutical agents.