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Lung cancer is the leading cause of death worldwide. Especially, non-small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efficient biomarkers for detection, diagnosis and prognosis. To find high efficient biomarkers for clinical diagnosis of NSCLC patients, we used gene differential expression and gene ontology (GO) to define a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down-expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were significantly down-expressed in tumor samples of stage 1. We used S-scores and N-scores defined in correlation networks to evaluate positive and negative influences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant effects and network effects globally impacting the other genes in expression and hence can be used as specific biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be differentially expressed and had very small S-scores and N-scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer. Our findings are well consistent with functions of these TS genes. GSEA analysis found that these 26 TS genes as a gene set had high enrichment scores at stages 1, 2, 3 and all stages. [ABSTRACT FROM AUTHOR]

Inhibition of c-MYC has been considered as a potential therapy for lymphoma treatment. We explored a lentiviral vector-mediated small interfering RNA (siRNA) expression vector to stably reduce c-MYC expression in B cell line Jijoye cells and investigated the effects of c-MYC downregulation on cell growth, cell cycle, and apoptosis in vitro. The expression of c-MYC mRNA and protein levels were inhibited significantly by c-MYC siRNA. The c-MYC downregulation resulted in the inhibition of cell proliferation and cell cycle arrest at G2/M phase, which was associated with decreased expression of cyclin B and cyclin-dependent kinase 1 (CDK1) and increased expression of CDK inhibitor p21 proteins. In addition, downregulation of c-MYC induced cell apoptosis characterized by DNA fragmentation and caspase-3 activation. Taken together, these results suggest that lentiviral vector-mediated siRNA for c-MYC may be a promising approach for targeting c-MYC in the treatment of Burkitt lymphoma. [ABSTRACT FROM AUTHOR]

Objective: We aimed to study the effect and mechanism of low-dose radiation (LDR) on adaptive response of gastric cancer cell. Methods: SGC7901 cells were cultured in vitro, and divided into 4 groups: control group (D0 group), low-dose radiation group (D1 group, 75 mGy), high-dose radiation group (D2 group, 2 Gy), low-dose plus high-dose radiation group (D1 + D2 group, 75 mGy + 2 Gy, the interval of low and high-dose radiation being 8 h). Cell inhibition rate was detected by cytometry and CCK8 method; the proportion of cell cycle at different times after irradiation was determined by using a flow cytometry. The ATM mRNA levels were detected by using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: There was no significant different between groups D0 and D1, groups D2 and D1 + D2 cell inhibition rate ( P > 0.05). There was a significant increase G2/M arrest in groups D2 and D1 + D2 than groups D0 and D1 after 6 h of radiation and did not recover at 48 h ( P < 0.05). The ATM mRNA expression of group D2 and D1 + D2 increased highly than that of group D0 and D1 ( P < 0.05). However, differences between group D2 and D1 + D2, group D0 and D1 were not statistical significant ( P > 0.05). Conclusion: LDR cannot induce adaptive response in SGC7901 cells in vitro, which may be associated the regulation of cell cycle, and its ATM mRNA expression cannot be affected by 75 mGy X-ray radiation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer (NSCLC). Methods: Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital (the Affiliated Hospital of Medical College Qingdao University, China) were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group (D1 + D2) and control group (D1). The control group (D1) only received radiotherapy to the chest; combined treatment group (D1 + D2) received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results: There was no significant difference in the ratio between two groups in cells CD4, CD8 and CD4/CD8 after radiotherapy ( P > 0.05). There was no change in these indicators in combined treatment group after treatment ( P > 0.05), but it decreased in control group ( P < 0.05). There was no significant difference in the incidences of radiation esophagitis, pneumonia, gastrointestinal reactions and bone marrow suppression between two groups ( P > 0.05), but the patients in combined treatment group seemed to tolerate high dose well ( P < 0.05). Conclusion: Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient's immune function. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to investigate the impact of abdominal hypo-fraction irradiation on liver damage in rats so as to provide a reference for its clinical application. Methods: A total of 100 Wistar rats were equally randomized to five groups as control, 4 Gy, 6 Gy, 8 Gy and 12 Gy group, and the corresponding fractionated doses were offered. Liver functions were examined at the 2nd, 4th, 6th, 8th and 10th week after irradiation. Morphological changes were observed by HE staining. Expressions of Bcl-2 and Bax were examined by immunohistochemical technique. Results: In all irradiation groups, hepatocellular swell, degeneration, necrosis and even hepatic fibrosis could be seen. The differences of the liver coefficient, Glutamyl pyruvic transaminase (GPT), Glutamyl oxaloacetic transaminase (GOT) were significant among the groups and different time points ( F = 11.833-781.972, F = 20.857-264.692, P < 0.001). Expressions of Bcl-2 and Bax were significantly different between each group ( F = 211.607, 116.577; P < 0. 001), and between each time point ( F = 54.083, 68.749; P < 0. 001). Conclusion: Compare with conventional fraction, abdominal hypo-fraction irradiation may cause radiation damage to rat liver, being dose-and-time dependent. Up-regulation of activating apoptosis protein Bax and down-regulation of inhibiting apoptosis protein Bcl-2 may involve in the process. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to discuss the effect of pre-low-dose X-ray radiation on P53, Bcl-2 and apoptosis of HepG2 cells in tumor-bearing nude mouse, and further explore the mechanism of low doses radiation. Methods: HepG2 cells were implanted subcutaneously into nude mice. 14 days after the implanting, these mice were divided into 6 groups randomly, S group (sham-irradiation 0 cGy), D1 group (7.5 cGy, dosage rate = 7.5 cGy/min), D2 group, (200 cGy, dosage rate = 100 cGy/min), D1 + 2 h + D2 group, D1 + 6 h + D2 group and D1 + 12 h + D2 group. Tumor-bearing mice in each experimental group were executed at 24 h after the last irradiation. P53 and Bcl-2 were detected by immunohistochemical staining, the tumor tissues apoptosis were detected in site (Tunel). Results: Each combined exposure groups (D1 + 2 h + D2 group, D1 + 6 h + D2 group and D1 + 12 h + D2 group) compared with the D2 group, the percentages of positive P53 and Bcl-2 were decreased obviously, and the apoptotic indexs were increased ( P < 0.01). Conclusion: Pre-low-dose radiation combined with the conventional radiation can increase the apoptosis of tumor tissues by decreasing the expression of P53 and Bcl-2, it can enhance the anti-tumor effect of conventional radiation, and it can have actual clinical significance on supporting radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate the clinical effects of concurrent radiochemotherapy in treating locally advanced (Stages III-IVa) nasopharyngeal carcinomas (NPCs). Methods: A total of 95 patients who suffered from nasopharyngeal carcinoma (Stages III-IVa) was divided into two groups: Group concurrent radiochemotherapy (Group CCRT, n = 49) and Group radiotherapy (Group RT, n = 46). The two groups were both delivered conventional fractionated radiotherapy, while Group CCRT was delivered three cycles chemotherapy of PF (DDP + 5-Fu) regimen or PLF (DDP + 5-Fu + CF) regimen. Results: The complete remission rate and total remission rate of Group CCRT were higher than those of Group RT, and the differences were of statistical importance (χ = 4.72-7.19, P < 0.05). The one-year overall survival (OS) rate was calculated by life table method, in Group CCRT, it was higher than that of Group RT and the difference was of statistical importance (χ = 4.24, P š 0.05). The 3-year overall survival (OS) rate, nasopharyngeal control rate and cervical lymph nodes' control rate of Group CCRT were all higher than those of Group RT and the differences were of statistical importance (χ = 4.28-4.40, P < 0.05). The 5-year overall survival (OS) rate and metastasis-free rate of Group CCRT were higher than those of Group RT and the differences were of statistical importance (χ = 3.96-8.26, P < 0.05). The incidence rates of acute toxicities in Group CCRT were obviously higher than those in Group RT, and the difference of gastrointestinal reaction was of statistical importance (χ = 11.70, P < 0.05). Conclusion: This study has demonstrated that concurrent radiochemotherapy can improve the remission rate, overall survival rate and locally control rate. The toxicities of concurrent radiochemotherapy can be tolerated by the patients. [ABSTRACT FROM AUTHOR]

Objective: By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens (PCNA), epidermal growth factor receptor (EGFR), erythropoietin (EPO) and vascular endothelial growth factor receptor (VEGFR) of tumor tissues in mice bearing S180 sarcoma, to further explore the mechanism of low doses radiation. Methods: S180 sarcoma cells were implanted subcutaneously into 58 male Kunming mice. Randomly these mice were divided into sham-irradiation (S) group and low-dose radiation (LDR) group. 12 days after implantation, the mice in LDR group were once delivered 75 mGy total-body Co γ-ray irradiation, while the mice in S group were left without irradiation. Then the mice in LDR group were executed at 6 h (LDR-6h group), 12 h (LDR-12 h group), 24 h (LDR-24 h group), 48 h (LDR-48 h group) and 72 h (LDR-72h group) after irradiation. Tumor tissues were weighed and histological observed. Immunohistochemical staining was used to detect the expression of PCNA, VEGF, EPO and VEGFR of tumor tissues. Results: Though there was no significant difference between LDR group and S group in tumor weight, after irradiation the expression of PCNA and EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from S group. The expression of EGFR and VEGFR also decreased, and LDR-24h group was the lowest ( P < 0.05). Conclusion: Seventy-two h after low-dose total body irradiation, there was no significant change in tumor size of mice bearing S180 sarcoma. Low-dose total body radiation decreased the expression of PCNA inhibiting tumor growth; reduced the expression of EGFR in tumor tissue impacting the signal transduction of tumor cells. The study also indicated that low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the molecular mechanism of anti-apoptotic action of survivin to the hepatoma-cellular carcinoma cell line HepG2. Methods: Design and synthesize siRNA gene sequence specifically targeting at HepG2 cell. HepG2 cells cultures were divided into five groups: blank control group, negative control group, low dose group, medium dose group and high dose group. HepG2 cells were treated respectively by pshRNA-survivin-387 of different concentrations. The apoptosis index (AI) was determined by flow cytometry (FCM). Cells were stained with rhodomine-123 (Rh123) to detect changes of mitochondrial membrane potentials. The concentration of cytoplasmic cytochrome C (Cyt.C) was continuously determined by ELISA. Relative activities of caspase-9 and caspase-3 were assessed by colorimetric assay. Results: Compared with the control group, due to the function of short interference RNAs (SiRNAs) that suppresses the survivin gene expression, the apoptotic index of transfected groups were significantly higher than those of control groups ( F = 13568.68, q = 110.47-327.16, P < 0.01), the apoptosis index of high concentration of transfected cells was higher than the low concentration transfected group ( q = 39.63-168.22, P < 0.01). The apoptosis index of high concentrations transfected HepG2 cells was 25.54%, higher than that of blank control group, negative control group, low dose group and medium dose group (5.24%, 6.61%, 12.63% and 15.64%, respectively). HepG2 cells transfected with SiRNA exhibit gradually decreasing mitochondrial membrane potentials, which then lead to the releasing of Cyt C, following it were the activation of caspase-9 and caspase-3. Conclusion: Survivin performs the function of anti-apoptosis to the HepG2 cells via modulating the apoptosis of mitochondrial. HepG2 cells transfected with SiRNA survivin can significantly induce apoptosis. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate the effects as well as the possible mechanisms of low dose y-ray pre-irradiation on hepatic damage, DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide (CTX). Methods: Kunming strain male mice were randomly divided into five groups: control group, sham-irradiated group, low dose irradiation group (LDR group), cyclophosphamide chemotherapy group (CTX group) and low dose irradiation combined with chemotherapy group (LDR + CTX group). Having being raised for one week, all the mice were implanted subcutaneously with S180 cells in the left inguen (control group excluded). On days 8 and 11, mice of LDR and LDR + CTX groups were given 75 mGy whole-body Y-irradiation, 30 h later mice of CTX and LDR + CTX groups were injected i.p. 3.0 mg cyclophosphamide. All the mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis (SCGE); ALT activity, total protein (TP) and albumin (ALB) of the plasma were analyzed using automatic biochemistry analyzer; MDA content, SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry; genetic material damage was analyzed using micronucleus frequency (MNF) of polychromatoerythrocytes (PCE) in bone marrow. Results: 1. Differences of MDA contents, SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance ( P < 0.01); in control group MDA content was the lowest, SOD and GSH-PX activity were the highest, while in CTX group MDA content was the highest, SOD and GSH-PX activity were the lowest; compared with CTX group MDA content decreased significantly ( P < 0.01) and SOD and GSH-PX activity increased significantly ( P < 0.05) in LDR + CTX group. 2. Differences of ALT activity of plasma between 5 groups had no statistical significance ( F = 1.262, P > 0.05). Differences of TP and ALB of plasma between 5 groups had statistical significance ( F = 12.879 and 6.336 respectively, P < 0.01); TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group, TP and ALB in LDR group elevated significantly ( P < 0.05). 3. Differences of DNA damage of peripheral lymphocytes had notable statistical significance ( F = 6.383, P < 0.01); DNA damage in control group was the lightest, while DNA damage in CTX group was the severest; compared with CTX group, DNA damage in LDR + CTX group was much lighter ( P < 0.05). 4. MNF of PCE between 5 groups had remarkable significance ( F = 179.652, P < 0.01); compared with control group and sham-irradiated group, MNF in CTX group increased significantly ( P < 0.01); compared with CTX group, MNF in LDR + CTX group had a tendency of decline, which had no statistical significance ( P > 0.05). Conclusion: 1. CTX can damage the hepatic tissue through oxidative stress; 75 mGy Y-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes, promote elimination of free radicals, so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy. 2. A 75 mGy Y-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma, but may have protective effect on the protein synthesis function of liver. 3. High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes; 75 mGy Y-irradiation before chemotherapy may have certain protective effect on DNA damage. 4. CTX has potent mutagenic effect, can cause significant increase of MNF of PCE; 75 mGy Y-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the effect of low dose radiation on cytokine excreted by mice inbreathing of atomization of PYM. Methods: Kunming male mice were randomly divided into three groups: blank group, PYM group (P group), low dose radiation + PYM group (P + L group). Mice of P + L group were given whole body low dose radiation 75 mGY, dose rate were 12.5 mGY/min. After 6 h, mice in both P + L group and P group were given inbreathe of atomization of PYM, concentration was 2 mg/mL. Mice were sacrificed after the d1, d7, d14, d21 and d28, IL-6 were detected in alveolar irrigating solution. The tissue samples of mice lung were fixed in 10% formalin, TNF-α and TGF-β were analyzed by immunohistochemistry. Results: Compared with P group, IL-6 in low dose radiation + PYM group were lower, near to blank group, the difference had notable statistical significance on the d1 and the d7, while on the d14, d21, d28, the difference had not statistical significance. It suggested that low dose radiation could reduce the resection of IL-6 at the begin of lung injure induced by low dose radiation. The expression of TGF-β and TNF-α in P + L group were lower than that in P group, but the difference in the two groups had statistical significance by gray analysis P < 0.05. Conclusion: In the early stage of lung injure caused by PYM in mice, low dose radiation of 75 mGY can reduce the secretion of IL-6, decrease the production of TGF-β and TNF-α. [ABSTRACT FROM AUTHOR]

Objective: To study the effects of low dose radiation (LDR) on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein Bcl-2 in tumor-bearing mice. Methods: Male mice of Kunming strain were implanted subcutaneously with S180 sarcoma cells in the left inguen as an in situ experimental animal model. Seven days later, the mice were subjected to 75 mGy whole-body γ-irradiation. At 24 and 48 h after the irradiation, all mice were sacrificed. The tumor sizes were measured, and tumor cell apoptosis and cell cycle progression were analyzed by flow cytometry. The expression of apoptosis-related protein Bcl-2 and the apoptotic rate of tumor cells were observed by immunohistochemistry and electron microscopy. Results: Tumors grew significantly slower after LDR (P<0.05). The tumor cells were arrested in G1 phrase and the expression of Bcl-2 protein decreased at 24 h. Apoptotic rate of tumor cells was increased significantly at 48 h after LDR (P<0.01). Conclusion: LDR could cause a G1-phase arrest and increase the apoptosis of tumor cells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. The organized immune function and anti-tumor ability are markedly increased after LDR. Our study provides practical evidence of clinical application to cancer treatment. [ABSTRACT FROM AUTHOR]

A peripherally inserted central catheter (PICC) provides an important access for patients requiring prolonged intravenous infusion. However, intravascular migration and subsequent malposition of a PICC may be caused by its flexibility and thinness and by changes in intrathoracic pressure and body position. In this report, we describe one case of persistent hiccup whose PICC migrated to and was bent and folded in the right subclavian vein. [ABSTRACT FROM AUTHOR]