In recent years, the study on the molecular mechanism of tumorigenesis and cancer cell signals promotes the application of cancer-targeted therapy, which aims at cell receptors, key genes, and regulatory molecules in cancer cells. However, the polymorphism of targeting genes/molecules determines the clinical efficiency of these therapies. The application of gene polymorphism diagnosis in cancer-targeted therapy was reviewed.

The current strategies of anti-cancer therapy are mainly based on the evidence-based medicine, which is much better than be based on the doctor's experience. But we still need to make attempts to find the right drugs and doses for each patient. The patients with the same disease may receive different response to the same treatment because of their inherited and somatic genetic variability. This results in greatly different therapeutic outcome. The determination of anti-cancer drugs and the doses based on the individual genotype will open up a new era of personalized therapy.

The growth factor receptor -bound protein-2 (Grb2) is an adapter protein in cells. Over expression of Grb2 is found in many kinds of tumor and plays an important role in tumor proliferation and progression. So it may be a molecular target for anti-tumor therapy.

Objective: To study the effect of bone marrow cells on myocardial regeneration. Methods: Bone marrow cells were implanted into the acute myocardial infarct via topical injection. Specimens were harvested at 1st, 2nd, 4th, 8th weeks after bone marrow cells implantation for morphologic examination. Results: Bone marrow cells with fluorescence had been observed in the implanted site. A portion of the implanted cells had differentiated into myogenic cells. The regenerating myocardial cells observed by electron micrography had been connected with the host myocardium through intercalated discs. The infarct size was significantly smaller in implant group. Conclusion: This study suggested that bone marrow cells are capable to differentiate and regenerate into myocardial cells in the acute myocardial infarct sites and reduce size of infarct.

ObjectiveTo study the effect of implantation of the bone marrow cells into infarction myo cardium on the secretion of basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), transforming growth factor-?1 (TGF-?1 ), interleu kin-1 (IL-1), and interleukin-8 (IL-8).MethodsBone marrow cells were implanted into the region of acute myocardial infarct via topical injection. Specimens were harvested at first, 2nd, 4th, 8th week after implantation for the expression of cytokines and vascular density examination by immunohistochemical analysis and the levels of cytokines by radioimmunoassay. ResultsAt first, 2nd, 4th, 8th week after transplantation, the vascular density in the bone marrow cell implant group was significantly higher than that in the control group (P

Objective:To study the alteration of K-ras mutations in different stages of colorectal cancer(CRC) and its influence on the progression of CRC. Methods:The 20 paraffin-embedded tissues, including primary foci, metastatic lymph nodes, remoter metastatic foci, colorectal adenoma, and normal colorectal tissues, were collected from 20 patients with colorectal cancer. The sequence of PCR-amplified products were analyzed. Results:The wild K-ras gene was expressed in normal colorectal tissues. The mutation frequency of K-ras gene was 20.0% (4/20) in colorectal adenoma, 30.0% (6/20) in primary foci, 25.0% (5/20) in metastatic lymph nodes, and 30% (6/20) in remote metastatic lesions. In the samples with K-ras mutations, the consistency of the types of K-ras mutations between primary foci and colorectal carcinoma, lymph node metastatic lesions, remote metastatic lesions was 0.0%(0/4), 40.0%(2/5), and 50.0%(3/6), respectively.Conclusion:The colorectal adenoma, metastatic lymph nodes and remote metastatic lesions were not suited for K-ras analysis as routine samples in clinical practice. If the samples of primary lesions were not available, the detection results of metastatic lymph nodes and remote metastatic remote lesions will provide some reference values. K-ras gene had several different mutations in the progression of CRC.

Objective To observe the expression of cytotoxicity and receptors on NK cells in breast cancer,and investigate the impact of soluble MICA(sohble MHC class Ⅰ-related molecules A,sMICA) on NK cells receptors expression and cytotoxicity.Methods ELISA was used to examine the sMICA in peripheral blood.The expressions of activated receptor(NKG2D),killer inhibitory receptor (KIR)(CD158b) and NK cells were identified by flow cytometry(FCM).Cytotoxicity of NK cells to breast cancer were tested by MTT.Results sMICA was (205.36±71.27)ng/L in breast cancer patients and 81.6 % samples were detected.There were positive correlations between sMICA levels with breast cancer stages.There were no difference of NK cells percentage between breast cancer and healthy person.The cytotoxicity of NK cells and expressions of NKG2D were obviously lower in breast cancer with sMICA(+) than in healthy person,but CD158b was higher in healthy person.After cultured with sMICA,NK cells cytotoxicity decreased from(76.2±6.7)% to(48.4±4.1)% and the expression of NKG2D reduced from(92.5±7.1)% to (62.5±6.4)%,but the the expression of CD158b increased from(10.6±3.2)% to (43.6±3.4)%.IL-15 up regulated the expression of NKG2D and NK cells cytotoxicity,but decreased the expression of CD158b by co-culturation with IL-15 and sMICA in sMICA+ patients with breast cancer.Conclusion sMICA reduced the expression of NKG2D and increased the expression of Kill,which lead to the down regulation of NK cells cytotoxicity.IL-15 can reverse this effect.

BACKGROUND: Hematopoietic stem cells have an ability of multi-directional differentiation and can be differentiated into megakayocytes in the presence of suitable hematopoietic growth factors and lineage special growth factors.Inducing of CD34+ stem cells to megakaryocytes in vitro involves many changes in gene expression, especially the signal transduction genes.OBJECTIVE: To study the expression of signal transduction genes after differentiation from stem cells into megakaryocytes.DESIGN: Open experiment.SETTING: Department of Tumor Immunology, Fujian Provincial Tumor Hospital.MATERIALS: 60-145 mL of cord blood was collected from normal labor fetuses under sterile conditions by using the blood-bag collective method. Patients and their relatives provided the confirmed consent. Reagents and equipments were detailed as follows: VarioMACS segregation apparatus, CD34+ Isolation Kit, SCGM serum-free medium, CD monoclonal antibodies, cytokines, human genome Oligo Set Version 2.1 from the CapitalBio Corporation, and LuxScan 10K/A bi-passage laser scanning apparatus. The researchers obtained consent from the local ethic committee.METHODS: This experiment was carried out in the Department of Tumor Immuonlogy, Fujian Provincial Tumor Hospital and the CaptialBio Corporation. from July 2005 to June 2006. RNA was extracted separately from CD34+ cells purified from cord blood and CD41+ cells induced from the same cord blood. The cDNA probes were synthesized by reverse transcription and purified. CD34+ cells before culturing and CD41+ cells after culturing were labeled with Cy3-dCTP and Cy5-dCTP respectively. Labeled DNA was dissolved in 30 μL hybridization fluid and hybridized at 42 ℃ over night MAIN OUTCOME MEASURES: The differential gene expression between haematopoietic stem cells and megakaryocytes involving cell signal transduction were detected by using DNA microarray analysis. According to the gene chip results,17 differentially expressed genes were selected for further analysis by RT-PCR.RESULTS: In this experiment, 3 522 differentially expressed genes were screened, including 1705 up-regulated genes and 1 817 down-regulated genes. In the 3 522 differentially expressed genes, there were 343 genes involved in cell signaling, 150 genes involved in transcription regulation, 21 genes involved in cell differentiation. The expression of the CD61 gene increased 369.83 fold, the expression of the CD41 gene increased 27.38 fold, and the expression of PF4 gene increased 24.06 folds; The expression of mitogen-activated protein kinases (MAPKs), G protein-coupled receptors (GPCRs) and members of RAS oncogene family increased mostly. The expression of the genes involved in STAT pathways, both SOCS1 and JAK2 were up-regulated, but STAT5A was down-regulated. As determined by the gene chip results, 17 differentially expressed genes were selected for further analysis by RT-PCR. GAPDH was used as the internal control, and RT-PCR results were in agreement and confirmed the finding from the gene chip expression results.CONCLUSION: Thrombopoeitin (TPO) and other hematopoietic growth factors may enhance the proliferation and differentiation of megakaryocytes derived from cord blood stem cells by GPCRs-Ras-MAPK pathway.

Objective: To explore the significance of Th17 in hepatocellular carcinoma, expecially with HBV infection.Methods:Cytometric bead array(CBA) was employed to detect 5 cytokines(IL-2,IL-4,IL-6,IFN-γ,IL-17A)from 39 tumor and non-tumor tissues of HCC and combined clinical data for comparative statistic analysis.Results:The expression of IL-2,IL-4,IFN-γin liver cancer tissue[(4.61±0.28),(3.37±0.58),(3.08±1.08)pg/ml,respectively] was significant lower than non-cancer tissue [(5.57±0.59),(3.77±0.70),(3.69±1.20)pg/ml,respectively].Otherwise,the expression of IL-6,IL-17A in cancer tissue [(280.09±254.68), (2.66±1.66) pg/ml, respectively] was higher than non-cancer [(6.58 ±1.92), (1.49 ±0.98) pg/ml, respectively].And,whatever cancer or non-cancer tissue,the expression of IL-17A in tissue[(3.45±1.86)pg/ml] with high HBV load (>1 000 U/ml) was significant higher than tissue with low HBV load[(1.97±1.16)pg/ml].Conclusion: IL-17A was highly expressed in HCC,and IL-2,IL-4,IFN-γmay inhibit its expression,and IL-6 may promote it.Hepatitis B virus infection may promote Th17 expression,thereby reducing patient′s prognosis.

Objective To analyze the influence of peptidimer-c on the gene expression profiling of K562 cells and investigate the mechanism of peptidimer-c inducing the apoptosis and inhibiting proliferation of K562cells.Methods Trypan blue staining technique was performed for counting the number of living K562 cells treated with peptidimer-c.The ultrastructure changes of K562 cells treated with peptidimer-c was observed under transmission electron microscope.The Human U133 Plus 3.0 gene chips were used to detect the differentially expressed genes of K562 cells treated with peptidimer-c.Reverse transcription PCR was conducted to confirm some genes identified by gene chips.Results Peptidimer-c could induce the apoptosis and inhibit the proliferation of K562 cells.Peptidimer-c caused widely changes of the gene expression profiles of K562 cells.The chip data suggested that there were 529 differentially expressed genes,of which 455 genes were up-regulated and 74 genes were down-regulated.The relevant apoptotic genes were down-regulated markedly,including JUN,AXUD1,TNFRSF10B,etc.Fifteen of the differentially expressed genes were detected by RT-PCR,which was consistent with the chip data.Conclusion Peptidimer-c may induce aooptosis of K562 cells by activating the TNF/TNFR family and the JUN family.