The Anti-tumor Immunity of Dendritic Cells Modified by IFN γ Gene on Mice Bearing Ascite Hepatoma Cell H22

1 Introduction Dendritc cell (DC)-based cancer vaccines have shown to been effective both in clinical trials and in animal tumor models. Some clinical trials have been on the phase Ⅲ , but some problems are challenging now. The functions of DC from patient with malignant tumor were depressed by tumor-secreting cytokines such as IL-10. it is critical to find out some methods to improve DC differentiation maturation for priming naive T cells and initiating the specific anti-tumor immunity effectively. IFNγ is a pluripotent cytokine that can exert more the expressions of different molecules in various cells. Now, some data have shown that DCs can produce IFNγ and IFNγ can promote the maturation of DCs, which plays very important roles in promoting protective immune response as the same as IFNγ produced in NK and NKT cells. In our research,we transfected IFNγ gene into DCs in order to investigate the effect of IFNγ on DCs and monitor the anti-tumor response of the tumor bearing mice after vaccination by IFNγ-modified DCs.     

MiR-148a inhibits angiogenesis by targeting ERBB3

MicroRNAs (miRNAs) play an important role in carcinogenesis in various solid cancers including breast can-cer. Down-regulation of microRNA-148a (miR-148a) has been reported in certain cancer types. However, the biological role of miR-148a and its related targets in breast cancer are unknown yet. In this study, we showed that the level of miR-148a was lower in MCF7 cells than that in MCF10A cells. V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) is a direct target of miR-148a in human breast cancer cells through direct binding of miR-148a to ERBB3 3’-UTR region. Overexpression of miR-148a in MCF7 cells inhibited ERBB3 expression, blocked the downstream pathway activation including activation of AKT, ERK1/2, and p70S6K1, and decreased HIF-1α expression. Furthermore, forced expression of miR-148a attenuated tumor angiogenesis in vivo. Our re-sults identify ERBB3 as a direct target of miR-148a, and provide direct evidence that miR-148a inhibits tumor an-giogenesis through ERBB3 and its downstream signaling molecules. This information would be helpful for target-ing the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the future.     

Thermographic Diagnosis for Curative Effect of Acupuncture and Qi-gong

Thermographic technique can be used to measure temperature distribution of body surface in real-time, non-contact and full-field, which has been successfully used in medical diagnosis, remote sensing, and NDT, etc. The authors have developed a thermographic experiment that can be applied to inspect the effect of action of acupuncture and qi-gong (a system of deep breathing exercises) by measuring the temperature of hand and arm. The observation is performed respectively by thermography for the dynamic changes of temperature of the arm and hand after acupuncture treatment and qi-gong treatment. Thermographic results show that the temperature on the collateral channels increases significantly. In the meantime, it can be seen that the above therapies of traditional Chinese medicine can stimulate the channel collateral system. This also contributes a new basis to the effect of action of the therapies of traditional Chinese medicine. The work shows that thermographic technique is a powerful tool for research in traditional Chinese medicine. In this paper, some thermal images are obtained from the persons treated with acupuncture and qi-gong.     

血管生成及其抑制剂在前列腺癌中的研究进展

Angiogenesis plays a key role in progression of prostate cancer. Antigiogenesis becomes a new treament target for prastate cancer. In this review, we focus on the current knowledge of angiogenesis and tumor angiogenesis inhibitor in prastate cancer.     

HDAC Inhibitors： A Potential New Category of Anti-Tumor Agents

Over the past years, it has been found that the epigenetic silence of tumor suppressor genes induced by overexpression of histone deacetylases （HDACs） plays an important role in carcinogenesis. Thus, HDAC inhibitors have emerged as the accessory therapeutic agents for multiple human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, growth arrest and apoptosis. To date, the precise mechanisms by which HDAC inhibitors induce cell death have not yet been fully elucidated and the roles of individual HDAC inhibitors have not been identified. Moreover, the practical uses of HDAC inhibitors in cancer therapy, as well as their synergistic effects with other therapeutic strategies are yet to be evaluated. In this review article, we discuss briefly the recent advances in studies of the developments of anti-cancer HDAC inhibitors and their potential clinical value.     

GM3-containing nanoparticles in immunosuppressed hosts:Effect on myeloid-derived suppressor cells

Cancer vaccines to date have not broadly achieved a significant impact on the overall survival of patients. The negative effect on the immune system of the tumor itself and conventional anti-tumor treatments such as chemotherapy is, undoubtedly, a key reason for these disappointing results. Myeloid-derived suppressor cells(MDSCs) are considered a central node of the immunosuppressive network associated with tumors. These cells inhibit the effector function of natural killer and CD8+ T cells, expand regulatory T cells and can differentiate into tumor-associated macrophages within the tumor microenvironment. Thus, overcoming the suppressive effects of MDSCs is likely to be critical for cancer immunotherapy to generate effective anti-tumor immune responses. However, the capacity of cancer vaccines and particularly their adjuvants to overcome this inhibitory population has not been well characterized. Very small size proteoliposomes(VSSP) is a nanoparticulated adjuvant specifically designed to be formulated with vaccines used in the treatment of immunocompromised patients. This adjuvant contains immunostimulatory bacterial signals together with GM3ganglioside. VSSP promotes dendritic cell maturation, antigen cross-presentation to CD8+ T cells, Th1 polarization, and enhances CD8+ T cell response in tumorfree mice. Currently, four cancer vaccines using VSSP as the adjuvant are in PhaseⅠand Ⅱ clinical trials. In this review, we summarize our work characterizing the unique ability of VSSP to stimulate antigen-specific CD8+ T cell responses in two immunocompromised scenarios; in tumor-bearing mice and during chemotherapy-induced leukopenia. Particular emphasis has been placed on the interaction of these nanoparticles with MDSCs, as well as comparison with other cancer vaccine adjuvants currently in preclinical or clinical studies.     

Manipulation of MHC-I/TCR interaction for immune therapy

Adoptive immunotherapy involving the transfer of autologous tumor or virus-reactive T lymphocytes has been demonstrated to be effective in the eradication of cancer and virally infected cells. Identification of MHC-restricted antigens and progress in generation of adaptive immune responses have provided new direction for such treatment for severe pathologies such as cancer and autoimmune diseases. Here we review the latest development about the molecular basis of MHC-I/TCR interaction, and it＇s manipulation including enhanced MHC-I expression, modification of peptide and engineered TCR for clinical applications such as vaccine design, tumor therapy and autoimmune diseases.     

EGFL7基因沉默对裸鼠乳腺癌血管生成的影响

Objective To investigate the effect of short hairpin RNA (shRNA) targeting at epidermal growth factor-like domain 7 (EGFL7) gene on angiogenesis of breast carcinoma and its mechanism in nude mice. Methods shRNA targeting at EGFL7 gene was constructed and transfected into SGC-7901 cells (pshEGFL7 group) , meanwhile , the cells transfected with vector plasmids were as a control group. Positive clones were selected and the transplanted tumor animal models constructed in nude mice , and the growth and volume of tumors were observed. After 8 weeks , EGFL7 mRNA and protein in transplanted tumor tissues were detected,and graded. Moreover, Anti-CD34, VEGF and TSP1 were stained by the immuno- chemistry method,and MMP-2 and TIMP2 mRNA were detected by RT-PCR. Results EGFL7 mRNA was down regulated significantly in the pshEGFL7 group. In the psh EGFL7 group, the tumor volume was ( 1.86 ± 0. 65) cm3, MVD was 20. 84 ± 6.38; while in the control group , tumor volume was (4.86 ± 1.15) cm3, MVD was 39.48 ± 9.01, In the EGFL7 group ,TSP1 protein presented positive , and VEGF protein presented weakly positive or negative.The expression of MMP-2 mRNA decreased ,TIMP2 mRNA increased in the pshEGFL7 group,and there were significant differences compared with the control group , P ＜ 0.01. Conclusion RNA interference targeting at EGFL7 gene can balance TSP1/VEGF, through regulating the expression of MMP-2/TIMP2 to impair angiogenesis of breast cancer in nude mice.