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Natural killer cells (NKs) have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells (PBMCs), stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.
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Humans , Immunotherapy , Methods , Killer Cells, Natural , Allergy and Immunology , Neoplasms , Pathology , Therapeutics , Treatment OutcomeABSTRACT
Objective To establish the rabbit model with hepatic VX-2 tumor and to investigate the intake of folate-conjugated silica-coated gold nanorods (GNRs@SiO2-FA) in experimental rabbits. Methods Under CT-guidance, animal model with VX-2 liver cancer was established in 27 rabbits by using puncture inoculation method. CT scanning and sonography were employed to observe the tumor growth. After two weeks, the rabbits were randomly and equally divided into blank control group (n=9, injection of saline), portal vein injection group (n=9, injection of GNRs@SiO2-FA) and intra-tumoral injection group (n=9, injection of GNRs@SiO2-FA). Every three rabbits from each group were sacrificed each time at 24 h, 48 h and 72 h after the treatment. The tumor tissue and the major organs were collected and sent for pathological examination. The cellular uptake of GNRs@SiO2-FA was studied by confocal laser scanning microscopy. Results The rabbit model of VX-2 liver cancer was successfully established. CT and sonography examination indicated that the tumor was rich in blood supply. Confocal laser scanning microscopy revealed that GNRs@SiO2-FA could specifically bind with tumor cells within 24 hours after injection, then the GNRs@SiO2-FA entered into the tumor cells and gathered in the tumor cytoplasm. Conclusion GNRs@SiO2-FA has highly targeted effect on the liver cancer cells in experimental animals, which has very important application prospect in targeting hyperthermia therapy and in 125I seed implantation therapy.
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AIM:To explore the polarized distribution of M 2 macrophages in the marginal region around lung adenocarcinoma , the marginal/central ratio and their effect on the prognosis .METHODS:Double immunohistochemistry staining was used to determine the distribution and the difference of CD 163 +/CD68 +( M2 ) macrophages in the marginal and central regions in 49 cases of lung adenocarcinoma in situ ( AIS), 11 cases of minimally invasive adenocarcinoma ( MIA) and 57 cases of invasive adenocarcinoma ( IA) in order to explore the effect and mechanism of the polarized distri-bution and the marginal/central ratio on the progression of lung adenocarcinoma .Single-factor Kaplan-Meier survival curve analysis and multivariate Cox survival analysis were employed to explore the relationship between the polarized distribution of M2 macrophages and the prognosis .RESULTS:Polarized aggregation of M 2 macrophages was observed in the marginal region of lung adenocarcinoma compared with that in the central region , and the difference was significant ( P<0.01 ) . Based on the median level , they were divided into high polarized group and low polarized group .In low polarized group , M2 macrophage count in AIS was not significantly different from that in MIA or IA .However, in high polarized group, M2 macrophage count in AIS was lower than that in MIA and IA in turn and there were statistically significant differences (P<0.01).Single-factor Kaplan-Meier survival curve analysis and log-rank test result showed that the number of M2 mac-rophages in the marginal region and marginal/central ratio were negatively correlated to the survival time (χ2 =44.71, P<0.01;χ2=21.75, P<0.01).Multivariate Cox survival analysis showed that the high polarized distribution of M 2 macro-phages in the marginal region and the marginal /central ratio were independent risk factors for the prognosis ( P<0.01 ) . CONCLUSION:There is a polarization effect of M2 macrophages on the marginal region of lung adenocarcinoma .The marginal polarization and the marginal/central ratio are independent risk factors of the prognosis .Therefore , it may be an effective method for the evaluation of the prognosis to judge the marginal polarization by preoperative puncture and to deter -mine the marginal/central ratio of M2 macrophages by postoperative biopsy .
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Objective To explore the possible mechanism of the apoptosis of hepatoma cell line HepG2 induced by the combination use of GNRs@SiO2-FA and 125I seeds and to discuss its relationship with Bcl-2 and Bax protein expressions so as to provide theoretical basis for clinical treatment of hepatic cancer with interstitial brachytherapy by using 125I seeds. Methods In vitro cultured HepG2 cells were randomly divided into 4 groups: blank control group (not treated), simple GNRs@SiO2-FA group, simple 125I seeds group, and combination group (GNRs@SiO2-FA plus 125I seeds). The apoptosis of HepG2 cells was determined by flow cytometry. The expression of Bax mRNA and Bcl-2 mRNA of HepG2 cells were tested by RT-PCR. The apoptosis-related genes (Bax and Bcl-2) and the tumor proliferation cell nuclear antigen (Ki67) proteins expression on HepG2 cells were examined with immunohistochemistry method. Results The flow cytometry examination showed that the apoptosis rate of HepG2 cells in the simple GNRs@SiO2-FA group and simple 125I seeds group was higher than that in blank control group (P<0.05), and the apoptosis rate of the combination group was significantly higher than that of the simple GNRs@SiO2-FA group and the simple 125I seeds group (P< 0.05). The expression level of Bax mRNA in the combination group was higher than that in the simple GNRs@SiO2-FA group and simple 125I seeds group, while the expression level of Bcl-2 mRNA in the combination group was obviously lower than that in the simple GNRs@SiO2-FA group and simple 125I seeds group. Bax protein was expressed on cytoplasm, Bcl-2 protein was expressed on cytoplasm and cell membrane, while Ki67 protein was expressed on nucleus. All of them presented as brown finely granular precipitations. Statistically significant differences in the amount of Bax, Bcl-2 and Ki67 protein expression existed between each other among the four groups (P< 0.05). The positive expression rate of Bax protein in the combination group was significantly higher than that of the simple GNRs@SiO2-FA group and the simple 125I seeds group, while the positive expression rate of Bcl-2 and Ki67 protein was significantly lower than that of the simple GNRs@SiO2-FA group and the simple 125I seeds group, and the differences were statistically significant (P < 0.05). Conclusion The combination use of GNRs@SiO2-FA and 125I seeds can more effectively induce the apoptosis of HepG2 cells. This effect may be accomplished through increasing the expression of Bax protein and inhibiting the expression of Bcl-2 and Ki67 proteins.
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BACKGROUND:Insulin-like growth factor 1 (IGF1) plays an important role in cellgrowth, proliferation and differentiation. Insulin-like growth factor binding protein 3 (IGFBP-3), as the main binding protein of IGF1, is involved in the regulation of IGF1. OBJECTIVE:To attempt to analyze the relation of IGFBP-3 and various diseases, and to explore the potential values of IGFBP-3 in disease diagnosis and risk assessment. METHODDatabases of PubMed, Science Direct and Wanfang database were retrieved with key words of“insulin-like growth factors 1;IGFBP-3;cancer;growth hormone deficiency;diabetes;osteoporosis”in English and Chinese, respectively, by screening titles and abstracts to search papers related to IGFBP-3 structure and function as wel as relationship of IGFBP-3 with cancer, growth hormone deficiency, diabetes, osteoporosis. Final y, 43 articles were summarized according to inclusion criteria. RESULTS AND CONCLUSION:In recent years, the relationship between gene of IGFBP-3 and risk of cancer is becoming a hot research topic. The results show that IGFBP-3 is a protective agent of cancer risk, and it is an important factor in evaluating the risk of cancer, exhibiting a potential application value. IGFBP-3 is also associated with growth hormone deficiency and diabetes. In addition, IGFBP-3 can assist IGF-1 to play the regulatory role in bone growth and differentiation, which is closely linked with osteoporosis. Therefore, IGFBP-3 can be a potential predictor for osteoporosis.
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Objective To develop a cancer cell targeting probe based on silica-coated gold nanorods and investigate its optics properties and its targeting effect on human hepatocellular carcinoma HepG2 cells in vitro.Methods Preparation of gold nanorods (GNRs) by seeded growth method,and then the spherical core-shell silica-coated gold nanorods were successfully prepared by a sol-gel method,finally the GNRs@SiO2 was conjugated with folate (GNRs@SiO2-FA).The characteristics of GNRs@SiO2-FA were studied using transmission electron microscopy,and UV spectra.The cells were divided into 2 groups randomly,adding GNRs@SiO2-FA and GNRs solution respectively at the gold concentration of 40.0 × 10-6,20.0 ×10-6,10.0 × 10-6,5.0 × 10-6,2.5 × 10-6,and the MTT method was applied to detect the absorbance (A value) and study the cytotoxicity of GNRs@SiO2-FA and GNRs.The cells were divided into 2 groups randomly,and incubated with the same concentration of GNRs@SiO2-FA and GNRs@SiO2 solution respectively,at 2,4,8,16,24 h,and the targeting of GNRs@SiO2-FA cellular uptake were detected by ICPMS by observing the process of GNRs@SiO2-FA into the cells by transmission electron microscopy (TEM).The data represented by (-x) ± s ; single factor analysis of variance were compared between the 2 groups ; and the differences were significant when P ＜ 0.05.Results UV spectrum confirmed the successful preparation of GNRs@SiO2-FA.The A value of the same concentration group was variance analysised,and the differences between the 2 groups was statistically significant (all P ＜ 0.01) with the gold element concentration from high to low:F =191.876,265.419,77.987,52.061,18.745.The ICP-MS confirmed GNRs@SiO2-FA could specifically bind with HepG2 cells.GNRs@SiO2 group gold element content at 2,4,8,16,24 h was (256.7±3.3),(602.8±2.4),(1067.1±3.6),(1998.5±4.3),(2078.5±1.3) mg/kg and GNRs@SiO2-FA group was(693.1 ±2.0),(1432.0 ±2.6),(2331.3 ±3.5),(2484.5 ±5.0),(2589.7 ±2.1)mg/kg,and the 2 groups was statistically significant (F =3278.070,34287.199,85434.870,18333.454,42412.973,P ＜0.01).TEM results showed that a small amount of nano probes were in the cytoplasm after cultured with GNRs@SiO2-FA cells 1 h,and that,a lot of probe were in the cytoplasm,4-24 h later,but there was no probe in the nucleus.Conclusion The prepared Folate-conjugated gold nanorods has good performance on biocompatibility and targeting.
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Objective To investigate the clinical significance of Notch-1 expression in small cell lung cancer(SCLC) and non-small cell lung cancer(NSCLC),and analyze the role of it in prognosis.Methods SP immunohistochemistry was used to detect the expression of Notch-1 antibody in 43 of SCLC and 40 of NSCLC tissues.Further analysis was carried out to interpret the association of Notch-1 antibody expression with clinicopathological features,lymph node metastasis and prognosis in SCLC.Results The positive rate of Notch-1 expression was 20.93％ ( 9/43 ) in SCLC,while 65.00％ ( 26/40 ) in NSCLC.The expression of Notch-1 antibody was associated with clinical stage and lymph node metastasis ( x2 =5.42,P ＜ 0.05 ; x2 =4.88,P ＜ 0.05respectively),but was not associated with age,sex,tumor location,tumor size ( Ps ＞ 0.05 ).Compared with NSCLC,the expression rates of Notch-1 antibody were significantly higher in SCLC ( x2 =16.50,P ＜ 0.05 ).Kaplan-Meier survival analysis indicated that the survival time of patients with positive Notch-1 expression was significantly longer than that of patients with negative staining( x2 =19.87,P ＜ 0.05 ).Cox regression analysis showed that Notch-1 antibody could significantly reduce the risk of death in patients with SCLC.Conclusion The positive expressions of Notch-1 were significantly different in SCLC and NSCLC,which linked to the clinicalstage,lymph node metastasis and poor prognosis.Accordingly,the expression of Notch-1 may have good value in diagnosis and prognosis.
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Objective:To evaluate the biological functions and underlying mechanisms of transcription factor PAX5 in promoting cell proliferation and anti-apoptosis in multiple myeloma cells.Methods:a PAX5 knockdown cell line was established by stable transfection of vector-based PAX5-siRNA into multiple myeloma IM9 cells.The expressing level of PAX5,p53,XBP-1 and c-Myc was examined by either or both Western blot and RT-PCR for the targets.Cell proliferation and apoptosis were assayed by MTT and flow cytometry,respectively.Results:PAX5 was expressed selectively in IM9 cells,but neither in another common used multiple myeloma KAS6 cells nor in the prostate cancer cells DU145 and PC3.Knockdown PAX5 led to a significant up-regulation of p53 and XBP1,but decreased c-Myc expressions in IM9 cells that were correlated with the increased sensitivity of drug-induced apoptosis and decreased proliferation rates when compared to the control cells.Conclusion:PAX5 is specifically expressed in IM9 cells,which promotes cell proliferation and anti drug-induced apoptosis.In addition to inhibiting the expression of p53 and XBP-1,PAX5 is found to induce expression of oncogene c-Myc in IM9 cells,and this finding indicates an undiscovered signal pathway that may contributes to the malignancy of Multiple Myeloma cells.