Analysis of Pediatric Oncology Nursing Research in Mainland China, 2008-2018.

BACKGROUND: Up-to-date research from low- and middle-income countries is needed to inform local pediatric cancer nursing care and share best practices from these settings. Access to all current Chinese-language publications on pediatric oncology nursing research is limited because of a language barrier. OBJECTIVE: The aim of this study was to document the volume, type of research study, and yearly and geographical distribution of published pediatric oncology nursing research in Mainland China and evaluate their content and quality. METHODS: A systematic search was performed for published pediatric oncology research conducted by nurses in Mainland China (2008-2018), using 3 English databases and 3 Chinese databases. Included articles were evaluated using the Johns Hopkins Nursing Evidence-Based Practice Research Evidence Appraisal for strength and quality of evidence. RESULTS: A total of 133 articles were included: 106 in Chinese and 27 in English. Most studies showed level III evidence (88/133) and were rated as good quality (81/133). The most frequently researched topics were psychosocial care, clinical nursing practice, and psychometric testing, which accounted for 63.2% of all publications. CONCLUSIONS: Progress in pediatric oncology nursing research capacity among Mainland China is promising. To gain higher-quality evidence and make existing evidence transferable for nursing practice, optimization of specific research topics is still needed. IMPLICATIONS FOR PRACTICE: In Mainland China, developing interventions to address the symptoms of children with cancer and caregivers' psychosocial issues based on local nursing research should be prioritized. Some synthesized findings of this review may serve as guidance for the future of pediatric oncology nursing science in similar settings.

The association between heated tobacco product use and cigarette cessation outcomes among youth smokers: A prospective cohort study.

INTRODUCTION: The U.S. Food and Drug Administration authorized the marketing of heated tobacco products (HTPs) with modified-risk information for adults on July 7, 2020. However, the effects of HTP use on cigarette cessation among youth smokers remain unclear. This study aimed to explore the association of HTP use with cigarette abstinence and cessation outcomes among youth smokers in Hong Kong who were willing to receive telephone counseling for smoking cessation. METHODS: This prospective cohort study included youth smokers aged ≤25 years who were enrolled in the Hong Kong Youth Quitline service. From December 1, 2016, to September 30, 2019, this study identified as HTP users 106 youth cigarette smokers who reported using HTPs on at least 1 of the past 30 days at enrollment, and identified as non-HTP users 473 smokers who reported smoking at least one conventional cigarette in the past 30 days and never using HTPs. The participants received follow-ups at 1 week and 1-, 3-, and 6-months postenrollment. The primary outcome was self-reported 7-day point prevalence of cigarette abstinence (PPA) at the 6-month follow-up. Secondary outcomes included reduction in cigarette smoking (excluding quitters), the number of cessation attempts, and the level of readiness to quit. RESULTS: The self-reported 7-day PPA was statistically significantly lower among HTP users than among non-HTP users after 6 months (19.0% vs. 34.2%; p = 0.009), with an adjusted relative risk of 0.47 (95% confidence interval: 0.24-0.91; p = 0.03). The study identified no significant differences in secondary outcomes between the two groups. CONCLUSIONS: Youth HTP users were less likely to abstain from tobacco use than their non-HTP-using counterparts. These results suggest that HTPs should not be promoted as smoking cessation or reduction aids among the youth population.

Psychological interventions for enhancing resilience in parents of children with cancer: a systematic review and meta-analysis.

PURPOSE: Caring for children with cancer is considerably stressful for parents and may negatively affect their physical and psychological well-being. Resilience plays a pivotal role in maintaining psychological well-being in the face of stress and adversity. The aim of this systematic review was to evaluate the effectiveness of psychological interventions in promoting resilience among parents of children with cancer. METHODS: Five English databases and two Chinese databases were subjected to a systematic search from inception to March 2020. The methodological quality of the included randomised controlled trials was evaluated using the Cochrane risk of bias tool (RoB 2.0). Meta-analyses and descriptive analyses were used. Subgroup analyses of the intervention modes and time since diagnosis were also conducted. RESULTS: Five studies involving 308 participants were included. The systematic review identified three types of psychological intervention, namely resilience training, self-disclosure and peer support, which had different essential components and characteristics. The meta-analyses of three randomised controlled trials revealed that the psychological interventions enhanced parents' resilience with a large effect size (Hedges' adjusted g 0.92; 95% CI 0.22, 1.62; p = .01). CONCLUSION: Evidence supports the effectiveness of psychological interventions for enhancing resilience in the parents of children with cancer. Healthcare professionals can incorporate evidence-based psychological interventions to enhance resilience to help these parents better navigate adversity, adapt to their children's situations and improve their psychological well-being.

Association of smoking behavior among Chinese expectant fathers and smoking abstinence after their partner becomes pregnant: a cross-sectional study.

BACKGROUND: Exposure to secondhand smoke (SHS) during pregnancy can cause pregnancy complications and adverse birth outcomes. About 40% of Chinese expectant fathers are smokers and they rarely attempt to quit smoking. There is a paucity of effective smoking cessation services targeting this population. In this study, we assessed the smoking behavior of Chinese expectant fathers and examined its association with smoking abstinence after their partner became pregnant, which is an essential prerequisite for designing effective smoking cessation interventions. METHODS: We conducted a cross-sectional survey in the obstetrics and gynecology clinic of three tertiary hospitals in China. Expectant fathers who smoked at least one cigarette per day for 1 month within the past 12 months were invited to participate in this study. The participants were asked to complete a structured questionnaire that assessed their smoking behaviors before and after their partner became pregnant. RESULTS: From December 2017 to March 2018, we recruited a total of 466 eligible expectant fathers, among whom 323 (69.3%) were identified as current smokers and 143 (30.7%) were ex-smokers. Using lasso regression, 19 features were selected from among 27 independent variables. The results of the selected multivariable logistic regression model showed that knowledge about the health hazards of smoking among smokers (odds ratio (OR) 1.39; 95% confidence interval (CI) 1.24 to 1.58; p < 0.001), knowledge about the health hazards of SHS to pregnant women (OR 1.46; 95% CI 1.09 to 1.97; p < 0.001), knowledge about harm to the fetus and newborn (OR 1.58; 95% CI 1.25 to 2.03; p < 0.001), and being a first-time expectant father (OR 2.08; 95% CI 1.02 to 3.85; p = 0.046) were significantly positively associated with smoking abstinence among expectant fathers after their partner became pregnant. Significantly negative associations were found for severe dysfunctionality in terms of family support (OR 0.48; 95% CI 0.24 to 0.95; p = 0.036) and smoking only outside the home (OR 0.81; 95% CI 0.26 to 0.98; p < 0.001). CONCLUSIONS: In this study, we identified several factors associated with smoking abstinence among expectant fathers after their partner became pregnant. These findings can guide the development of effective interventions targeting expectant fathers, to help them quit smoking.

An evaluation of a positive psychological intervention to reduce burnout among nurses.

This quasi-experimental study aimed to evaluate the positive psychological intervention of recording three good things on alleviating nurses' burnout. Eighty-seven nurses with burnout were recruited. Nurses in the study group recorded three good things using communication tool WeChat for six months, no records were made in the control group. After intervention, the score of exhaustion decreased considerably for nurses in the study group. Nurses recording three good things on average twice a week returned the lowest score of exhaustion. This intervention combined with appropriate surveillance and encouragement is recommended to reduce nurses' burnout and create a positive work environment.

Burnout and its association with resilience in nurses: A cross-sectional study.

AIMS AND OBJECTIVES: To investigate the prevalence and extent of burnout on nurses and its association with personal resilience. BACKGROUND: With the worldwide shortage of nurses, nurse burnout is considered one of the main contributing factors and has been the focus of studies in recent years. Given the well-documented high level of burnout among nurses, resilience is expected to be a significant predictor of nurse burnout. The association between burnout and resilience has not previously been investigated extensively. DESIGN: A cross-sectional survey design was selected. METHODS: A total of 1,061 nurses from six separate three-level hospitals in Hunan Province, China, returned self-reported questionnaires from March-June 2015. Data were collected using a socio-demographic sheet, Maslach Burnout Inventory-General Survey and the Connor-Davidson Resilience Scale. RESULTS: Nurses experienced severe burnout symptoms and showed a moderate level of resilience. Three metrics of burnout had significantly negative correlations with the total score and following variables of resilience. Linear regression analysis showed resilience, especially strength, demographic characteristics (exercise, alcohol use and marital status) and job characteristics (income per month, ratio of patients to nurses, shift work and professional rank) were the main predictors of the three metrics of burnout. CONCLUSION: The findings of this study may help nurse managers and hospital administrators to have a better understanding of nurse burnout and resilience. The significantly negative relationship between burnout symptoms and resilience has been demonstrated, and this informs the role of resilience in influencing burnout. RELEVANCE TO CLINICAL PRACTICE: Adaptable and effective interventions for improving resilience are needed to relieve nurses' burnout and reduce workplace stress. Moreover, nurse managers and hospital administrators should establish an effective management system to cultivate a healthy workplace and adopt positive attitudes and harmonious relationships.

Exploring resilience in Chinese nurses: a cross-sectional study.

AIMS: To explore the state of resilience and its predictors among nurses in mainland China. BACKGROUND: Resilience is considered as an important ability to influence the prevention of job dissatisfaction and burnout. There are few studies on resilience in Chinese nurses, particularly investigating the predictors of resilience. METHODS: A cross-sectional survey was employed and 1061 nurses from six three-level hospitals in Hunan responded to participate in the study. Data were collected using self-reported questionnaires. RESULTS: Nurses experienced moderate levels of resilience and self-efficacy and tended to use a positive coping style. Multiple linear regression showed that a high level of self-efficacy and education, having a positive coping style rather than a negative coping style, exercising regularly and not using cigarettes predicted a high level of resilience (P < 0.01). CONCLUSION: This study shows a moderate level of resilience among nurses and suggests that a high level of self-efficacy and education, as well as having a positive coping style and choosing a healthy lifestyle may increase nurses' resilience. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators and nursing managers need to explore the resilience state among nurses and understand the predictors of resilience. Then, scientific and evidence-based interventions for improving resilience should be adopted.

Latent classes of resilience and psychological response among only-child loss parents in China.

Only-child loss parents in China recently gained extensive attention as a newly defined social group. Resilience could be a probable solution out of the psychological dilemma. Using a sample of 185 only-child loss people, this study employed latent class analysis (a) to explore whether different classes of resilience could be identified, (b) to determine socio-demographic characteristics of each class, and (c) to compare the depression and the subjective well-being of each class. The results supported a three-class solution, defined as 'high tenacity-strength but moderate optimism class', 'moderate resilience but low self-efficacy class' and 'low tenacity but moderate adaption-dependence class'. Parents with low income and medical insurance of low reimbursement type and without endowment insurance occupied more proportions in the latter two classes. The latter two classes also had a significant higher depression scores and lower subjective well-being scores than high tenacity-strength but moderate optimism class. Future work should care those socio-economically vulnerable bereaved parents, and an elastic economic assistance policy was needed. To develop targeted resilience interventions, the emphasis of high tenacity-strength but moderate optimism class should be the optimism. Moderate resilience but low self-efficacy class should be self-efficacy, and low tenacity but moderate adaption-dependence class should be tenacity.

Latent Profiles of Posttraumatic Growth and Their Relation to Differences in Resilience among Only-Child-Lost People in China.

AIMS: Since the early 1980s, the one-child policy has been implemented nationwide in China. A special group called the "only-child-lost family" (OCL family) has emerged and has become a social phenomenon that cannot be ignored. We report latent profiles of posttraumatic growth and their relation to differences in resilience among OCL people in China. METHODS: A total of 222 OCL people were investigated using the Posttraumatic Growth Inventory and the Connor-Davidson Resilience Scale. Latent profile analysis was applied to explore PTG latent profiles. Multinomial logistic regression was used to analyze the socio-demographic variables in each latent profile and the association between profile membership and resilience. RESULTS: Three latent profiles were identified and labeled the "high appreciation-power group" (30.6%), the "general moderate growth group" (47.7%) and the "low growth and extreme possibility group" (21.7%). Compared to those in the high appreciation-power group, individuals with monthly income >2000 ($312) were less likely to be in the general moderate growth group (OR = 0.13, P<0.01), whereas individuals with a spouse were less likely to be in the low growth and extreme possibility group (OR = 0.43, P<0.01). Individuals in the "general moderate growth group"(OR = 0.92, P<0.01, 95%CI:0.89-0.94) and the "low growth and extreme possibility" groups (OR = 0.83, P<0.01, 95%CI:0.79-0.87) demonstrated significantly lower levels of resilience compared to the high appreciation-power group. CONCLUSION: The PTG patterns in only-child-lost parents were varied. Promoting resilience may be a way to foster these parents' PTG. Targeted intervention should be developed based on the characteristics of each latent class, and timely attention must be paid to the mental health of OCL parents who are without a spouse and have low income.

Induction of anti-tumour immunity by dendritic cells transduced with hTERT recombinant adenovirus in mice.

Dendritic cells (DCs) transfected with recombinant, replication-defective adenovirus (Ad) vectors encoding the human telomerase reverse transcriptase (hTERT) are potent inducers of cytotoxic T lymphocytes (CTLs) and anti-tumour immunity. However, previous studies have mostly been in vitro. In this study, we sought to determine whether DCs transfected with hTERT (DC/Ad-hTERT) could elicit a potent anti-tumour immunogenic response in vivo. We found that murine DCs transfected with recombinant adenovirus encoding the hTERT gene (DC/Ad-hTERT) induced hTERT-specific CTLs in vivo effectively, compared with Ad-LacZ-transduced DC (DC/Ad-LacZ) controls. These hTERT-specific CTLs lysed various tumour cell lines in an hTERT-specific and MHC-I molecule-restricted fashion. We also found that DC/Ad-hTERT could increase antigen-specific T-cell proliferation and augment the number of IFN-gamma secreting T-cells in mice. These data suggest that the DC/Ad-hTERT vaccine may induce anti-tumour immunity against tumour cells expressing hTERT in an MHC-I molecule-restricted fashion in vivo through the augmentation of the hTERT-specific CTL response. The DC/Ad-hTERT vaccine may thus be used as an efficient DC-based tumour vaccine in clinical applications.

Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro.

Telomerase activity is detected in more than 90% of examined tumors but not in most normal somatic cells. Among three subunits of human telomerase, human telomerase reverse transcriptase (hTERT) is the rate-limiting component for telomerase activity. Therefore, targeting hTERT represents a promising approach for diminishing telomerase function that will probably not cause substantial side effects on telomerase negative somatic cells. To explore the effects of antisense hTERT (ahTERT) on the malignant phenotypes of human SGC-7901 gastric cancer cell line in vitro, an antisense eukaryotic expression vector of hTERT was constructed by gene recombinant technology. Telomerase activity by telomeric repeat amplification protocol-ELISA, mRNA of telomerase subunits, c-myc and bcl-2 by reverse transcript-PCR, terminal restriction fragment (TRF) by Southern blot, cell cycle distribution by flow cytometry and protein expression of hTERT, c-myc and bcl-2 by Western blot were analyzed in SGC-7901 cells before and after transfection. Cloning efficiency assay in soft agar and tumorigenesis in nude mice were also examined and evaluated in the above cells. The results demonstrated that after ahTERT transfection, the proliferation of SGC-7901 cells was significantly inhibited. Further study showed that telomerase activity, telomere length, the mRNA and protein expression of hTERT, bcl-2 and c-myc were decreased in ahTERT-transfected cells. There were, however, no obvious effects on transcription of human telomerase RNA (hTR) and human telomerase associated protein1 (TP1) in both transfected and untransfected cells. Flow cytometric analysis displayed an accumulation of G0/G1 phase and a decreasing proliferation index (PI) in ahTERT-transfected cells. Moreover, no tumorigenicity was found after subcutaneous injection of ahTERT-transfected cells in nude mice, whereas palpable tumors were observed in mice injected with control cells. Our study indicates that exogenous ahTERT can inhibit proliferation and partially reverse malignant phenotypes of SGC-7901 cells via the suppression of telomerase activity, hTERT, c-myc and bcl-2 expression. Antisense technology targeted hTERT strategy might be a potential approach for gastric cancer therapy.

KAI1 gene suppresses invasion and metastasis of hepatocellular carcinoma MHCC97-H cells in vitro and in animal models.

BACKGROUND: Downregulation of KAI1 gene expression has been found in many types of cancer cells and is closely related to cancer invasion and metastasis. This study was aimed at investigating the effects and possible underlying mechanisms of KAI1 gene on invasion and metastasis of human hepatocellular carcinoma (HCC). METHODS: The invasive ability, visco-elastic properties and cell adhesion forces were analysed in different HCC cells originating from the MHCC97-H cell line transfected with either the sense or the antisense KAI1 expression plasmid. Tumuorigenicity, metastatic abilities, extracellular matrix (ECM) and intercellular adhesion molecule-1 (ICAM-1) expression were also evaluated in the nude mouse models of the xenografted and orthotopic liver cancer cells. RESULTS: Compared with their parental cells, in the HCC cells transfected with the sense KAI1 gene, the invasive ability in vitro was significantly decreased (P<0.01); the cellular elastic coefficients K(1), K(2) and mu were significantly higher (P<0.05); the cells adhesion forces to fibronectin were significantly lower (P<0.01). The sense KAI1 gene transfection into the cancer cells also inhibited their invasion and lung metastasis in the orthotopic liver cancer nude mice. However, the opposite changes were observed in the HCC cells transfected with the antisense KAI1 gene. KAI1 gene transfection also affected ECM and ICAM-1 expression in the transplanted liver cancer. CONCLUSION: The KAI1 gene plays an important role in the invasion and metastasis of human HCC and its upregulation in HCC cells suppresses their invasive and metastatic abilities. KAI1 gene functioned as a metastasis inhibitor by regulating the HCC cell biophysical behaviours including aggregation, adhesion, motility and visco-elastic properties.

Dendritic cells reconstituted with a human heparanase gene induce potent cytotoxic T-cell responses against gastric tumor cells in vitro.

BACKGROUND AND AIMS: Dendritic cell-based tumor vaccination is a promising approach in the treatment of cancer. Strategies to modify dendritic cells (DCs) with tumor-associated antigens (TAAs) can elicit specific immune responses against tumors. Heparanase is overexpressed in gastric cancer, especially in invasive and metastatic cells, but is downregulated in differential normal tissue. Therefore, heparanase is a potential target in immunotherapy for patients with advanced gastric cancer who are not candidates for surgery. The present paper was designed to investigate the immune response of a heparanase gene-modified DC-based vaccine against gastric cancer cell lines in vitro. METHODS: DCs from peripheral blood mononuclear cells of healthy HLA-A2-positive donors were transfected with recombinant adenovirus containing the full-length cDNA of heparanase (rAd-Hpa) to generate heparanase gene-modified DC vaccine. T lymphocytes from the same donors were repeatedly activated by genetically modified DC vaccine to generate heparanase-specific cytotoxicity T lymphocytes (CTLs). CTL-mediated cell lysis of gastric cancer cells lines (KATO-III and SGC-7901) was analyzed in vitro by a standard (51)Cr releasing assay. IFN-gamma secretion was measured by ELISA in heparanase-specific CTLs cocultured with those gastric cancer cell lines. RESULTS: Our results showed that the expression of heparanase in DCs transfected with rAd-Hpa was significantly increased. Furthermore, DCs transfected with rAd-Hpa could induce heparanase-specific CTLs against HLA-matched and heparanase-positive gastric cancer cells in vitro, while there were no killing effects on autologous lymphocytes. Meanwhile, these rAd-Hpa-modified DCs could increase IFN-gamma secretion of effector cells when cocultured with KATO-III cells. CONCLUSIONS: These findings demonstrate for the first time that the transduction of DCs with rAd-Hpa can induce CTLs that specifically lyse heparanase-positive gastric cancer cells and increase IFN-gamma secretion in an MHC-restricted fashion. Heparanase gene-modified DC vaccine offers a great opportunity for immunotherapy in patients with advanced gastric cancer and possibly also with other malignancies.

Helicobacter pylori infection induces apoptosis in gastric cancer cells through the mitochondrial pathway.

BACKGROUND AND AIMS: To clarify the role of the mitochondrial pathway in apoptosis induced by H. pylori infection in gastric epithelial cells. METHODS: Cells of a gastric adenocarcinoma cell line SGC-7,901 were co-cultured with H. pylori NCTC 11,637, with or without preincubation with the inhibitors of caspases -3, -8, and -9. Apoptosis was determined by flow cytometry. RT-PCR was used to determine the expression of Bid, Bax, and Bcl-2 mRNA, and Western blotting was used to determine the expression of Bid, Bax, and Bcl-2 proteins, and the activation of caspases -3 and -9. RESULTS: H. pylori directly induced apoptosis in SGC-7,901 cells. Apoptotic indices (AIs) were 6.30 +/- 0.40%, 11.57 +/- 0.78%, 8.63 +/- 0.67%, and 7.22 +/- 0.97%, respectively, at 6, 12, 24, and 48 h after SGC-7,901 cells were co-cultured with H. pylori. H. pylori up-regulated the expression of Bid and Bax at both protein and mRNA levels, and induced a time-dependent activation of caspases -3 and -9. Apoptosis was inhibited significantly by the preincubation of SGC-7,901 cells with the inhibitors of caspase-3 (AIs were 1.72 +/- 0.59%, 2.97 +/- 0.55%, 4.38 +/- 1.56%, and 3.29 +/- 0.83%, respectively, at 6, 12, 24, and 48 h), and caspase -9 (AIs were 2.47 +/- 0.53%, 6.68 +/- 0.47%, 5.97 +/- 0.46%, and 5.43 +/- 0.15%, respectively, at 6, 12, 24, and 48 h). The caspase-8 inhibitor also reduced H. pylori-induced apoptosis by 20%. CONCLUSIONS: H. pylori infection induces apoptosis and the activation of caspases -3 and -9 in gastric cancer cells. Moreover, the caspase inhibitors significantly suppress H. pylori-induced apoptosis. These findings suggest that the mitochondrial pathway may be the major pathway in H. pylori-induced apoptosis in gastric epithelial cells.

In vitro anti-tumor immune response induced by dendritic cells transfected with hTERT recombinant adenovirus.

Transduction with recombinant, replication-defective adenoviral (Ad) vectors encoding a transgene is an efficient method for gene transfer into human dendritic cells (DC). Several studies have demonstrated that epitopes of the human telomerase reverse transcriptase gene (hTERT) can produce CTLs specific for malignant tumors. In this study, we constructed an hTERT recombinant adenovirus (rAd-hTERT) using DNA recombination. We found that human dendritic cells transduced with rAd-hTERT could effectively induce hTERT-specific cytotoxic T lymphocytes (CTLs) in vitro against various tumor cell lines, which were hTERT-positive and HLA-A2 matched. We also found that these hTERT-specific CTLs could not lyse autologous lymphocytes with low telomerase activity. Further studies revealed that rAd-hTERT transduced DCs could increase secretion of IFN-gamma by effector cells when they were co-cultured with hTERT-positive and HLA-A2 matched tumor cell lines. These data suggest that an hTERT vaccine can induce anti-tumor immunity against various tumor cells expressing hTERT in a HLA-A2-restricted fashion in vitro. The transduction of DCs with rAd-hTERT offers a great opportunity in cancer immunotherapy.

[Effects of hTERT RNAi on apoptosis of hepatocellular carcinoma cells induced by TRAIL].

OBJECTIVE: To study the effects of human telomerase reverse transcriptase (hTERT) RNA interference (RNAi) on biological characteristics of hepatocellular carcinoma cell lines HepG2 and SMMC-7721 and on apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). METHODS: Small hairpin hTERT (shTERT) sequence was identified by PCR method; hTERT expressions, morphological features, cell proliferation and replicative senescence were respectively determined using RT-PCR, hematoxylin-eosin (HE) staining, growth curve and beta-galactosidase (b-Gal) staining; cell cycle and apoptosis were identified using flow cytometry after propidium iodide (PI) staining and annexin V/PI double staining. RESULTS: shRNA were found in 6/8 HepG2 and 6/6 SMMC-7721 cell clones transformed by the recombined plasmid pSilencer 3.1-H1 neo-shTERT. The interference rates of hTERT on HepG2 and SMMC-7721 were 100% and 43.3% respectively. Cells in G2-M phases increased from 7.1% to 10.6% and from 6.9% to 7.9% respectively; and the percentage of replicative senenscence cells increased from 0 to 20.4% and from 3.6% to 10.0% respectively. The nucleus/cytoplasm ratios of the cells were obviously decreased after hTERT RNAi treatment. Moreover, apoptosis of hepatocellular carcinoma cells and apoptosis induced by TRAIL were strikingly increased by hTERT RNAi (P < 0.05). For example, apoptosis rates were increased from 3.5% to 5.2% in HepG2 cells and from 4.8% to 7.9% in SMMC-7721 cells after hTERT RNAi treatment. Apoptosis rates were increased from 5.3% to 10.4% in HepG 2 cells and from 13.9% to 77.2% in SMMC-7721 cells after being treated by 100 ng/ml TRAIL for 24 h. However, there were no remarkable changes between control cells and untransformed cells. CONCLUSION: hTERT RNAi not only has a significant effect on biological characteristics of hepatocellular carcinoma cells, but also obviously can increase cell apoptosis induced by TRAIL.

[Immune response of heparinase gene modified dendritic cell-based vaccine on gastric cancer cells].

OBJECTIVE: To explore the feasibility of heparinase vaccine in active immunity for gastric cancer. METHODS: Dendritic cells originated from the peripheral blood mononuclear cells (PBMC) of healthy HLA-A2 positive donors were transfected with recombinant adenovirus containing heparinase full length cDNA of heparanase to generate heparanase gene modified DC vaccine. T lymphocytes from the same donors were activated by those genetically modified DC vaccine repeatedly to generate heparanase specific cytotoxicity T lymphocytes (CTL). CTL-mediated cell lysis to gastric cancer cells of the lines KATO-III and SGC-7901 was analyzed in vitro by standard (51)Cr releasing assay. Heparinase specific CTL were co-cultured with KATO-III and SGC-7901 cells, and then ELISA was used to detect the IFN-gamma release. RESULTS: Expression of heparanase was significantly increased in the DCs transfected with heparinase recombinant adenovirus. Heparanase specific CTL generated from the genetically modified DC vaccine exhibited potent lysis to the KATO-III gastric cancer cells positive in both heparinase and HLA-A2 at each E/T ratio, whereas, these heparinase specific CTL could not lyse the SGC-7901 cells positive to heparinase but negative to HLA-A2, with a specific lysis rate of only 11.1% +/- 4.6% even at an E:T ratio of 40:1. Further study showed that heparanase vaccination had no detectable lysis on the autologous lymphocytes in vitro with a specific lysis rate of only 11.4% +/- 7.9% even at an E:T ratio of 40:1. The IFN-gamma release amount when the heparanase specific CTL were co-cultured with the KATO-III cells was 280.4 pg/ml +/- 23.5 pg/ml, significantly higher than that when the heparanase specific CTL were co-cultured with the rAd5-Lacz modified DC (120.6 pg/ml +/- 18.9 pg/ml), and that of the IL-2 stimulated T cells (60.0 pg/ml +/- 10.6 pg/ml, both P < 0.05). In contrast the IFN-gamma release amounts of the SGC-7901 cells and autologous lymphocytes remained unchanged when they were co-cultured with either above-mentioned effector cells (both P > 0.05). CONCLUSION: DC genetically modified by heparanase gene activate heparanase specific CTL and induce potent immune response against HLA-matched and heparinase positive gastric cancer cells in vitro, whereas they have no killing effect on autologous lymphocytes. Heparanase is an effective and safe target for immunogen therapy of tumor, thus providing a new biotherapy method for advanced gastric cancer.

[Difference analysis of genome-wide DNA methylation status of CpG islands between the monozygotic twins with disconcordant phenotypes of chronic hepatitis B virus infection].

OBJECTIVE: To analyse the difference of genome-wide DNA methylation status of CpG island between the monozygotic twins with disconcordant phenotype of HBV infection and to discover possible differentially methylated genes. METHODS: Modified AIMS (amplification of inter-methylated sites) method was adopted. According to the frequent sites of CpG islands (-CGCG- and -CCGG-), three groups of isochizomers with distinct methylation sensitivity (Sma I-Xma I, Hpa II-Msp I and BssH II-Pau I/BseP I) were used to modify the AIMS method. The modified AIMS method combined with Personal Molecular Imager FX system analysis and radioautographic analysis was used to make the global detection of the methylome of CpG islands. Multiple anonymous bands were compared between the twins with the Quantity One bio-soft. The different bands were cloned into T vectors and positive clones were sequenced. BLAST analysis of positive clone sequences was conducted to give the clues for the differential methylated genes between monozygotic twins with discordant phenotype of HBV infection. RESULTS: Nearly the same bands were found between one pair of twins with concordant phenotype of HBV infection. Different methylated bands were found not only between monozygotic twins with concordant phenotype but also between those with disconcordant phenotype. More differential methylated bands were found in the latter groups. By BLAST analysis with sequences of differential methylated bands, four possible genes were got. These genes might relate to the monozygotic twins with disconcordant phenotype of chronic HBV infection. CONCLUSION: Differential methylation of genes occurs in monozygotic twins with discordant phenotype of HBV infection. Whether these changes are involved in the pathogenesis of different phenotypes needs further elucidation.