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Terms such as spirituality and spiritual needs are abstract and difficult to understand. Realization of spirituality of hospice patients was premise in addressing expression of their spiritual needs. This study investigated expectations expressed during life review and tried to prove that the expectation was intelligible term for spiritual needs in Chinese hospice from May 2011 to June 2013. Among the 107 recruited patients, families were the most frequent emotion-expressing recipients, and 133 expectations related to patients' spiritual needs were identified. The emotion-expressing recipients and the patient's expectations were not affected by demographic characteristics. The expectations in life review with hospice patients and their families had the features of spiritual essence. The identified expectation contents could be used to address spiritual needs in hospice care in Chinese., (© The Author(s) 2014.)

Objective: We discussed the correlation between SNP loci (rs198389 and rs198388) in brain natriuretic peptide gene (NPPB) and susceptibility to congenital heart diseases (CHD)., Method: Multiplex SNaPshot technique was adopted for profiling of SNP genotypes at loci rs198389 and rs198388 in NPPB gene among 150 cases of CHDand 150 normal controls., Results: The distribution frequency of 3 genotypes (AA, AG and GG) at locus rs198389 was 40.7%, 36.0% and 23.3% in CHD group, respectively, showing significant differences compared with the normal controls (P<0.001). Gallele was associated with higher risk of CHD (OR=2.48, 95% CI=1.77-3.48). The distribution frequency of CC, CTand TT genotypes at locus rs198388 was 60.7%, 17.3% and 22.0% in CHD group, respectively, also showing significant differences compared with the normal controls (P<0.001). C allele could increase the risk of CHD (OR=1.92, 95% CI=1.48-2.48)., Conclusion: SNP loci rs198389 and rs198388 in NPPB gene were correlated with genetic susceptibility to CHD.

Protection of telomeres 1 (POT1) is a telomere-binding protein, which binds to the single-stranded DNA extensions of telomeres and regulates telomere length. Different POT1 mRNA variants were examined and compared with telomere length and radiosensitivity in colon and gastric adenocarcinoma cells. POT1 production and telomere lengths were assessed using 10 human cancer cell lines by quantitative polymerase chain reaction (qPCR). POT1 mRNA levels, which were relatively stable, were significantly correlated with telomere length in gastric cancer cells and colon cancer cells, except for HT29 (P<0.01). POT1 v5 indexes were closely associated with radiosensitivity in colon cancer cells and gastric cancer cells (P<0.05). In conclusion, POT1 may be a good marker for the examination of cell-specific telomere length and radiosensitivity.

Background: The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis., Methods: Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value <0.05 was considered to be significant., Results: The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P<0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P<0.001), clinical stage (P<0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR =2.244, P=0.028)., Conclusions: The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC.

Streptochlorin, first isolated as a new antibiotic in 1988 from the lipophilic extracts of the mycelium of a Streptomyces sp, is an indole natural products with a variety of biological activities. Based on the methods developed for the synthesis of pimprinine in our laboratory, we have synthesized a series of indole-modified streptochlorin analogues and measured their activities against seven phytopathogenic fungi. Some of the analogues displayed good activity in the primary assays, and the seven compounds 10b, 10c, 11e, 13e, 21, 22c and 22e (shown in Figure 1) were identified as the most promising candidates for further study. Structural optimization is still ongoing with the aim of discovering synthetic analogues with improved antifungal activity., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Telomere length is closely associated with cellular radiosensitivity and WRAP53 is required for telomere addition by telomerase. In this research we assessed radiosensitivity of laryngeal squamous cell carcinoma Hep-2 cell lines after WRAP53 inhibition, and analyzed the molecular mechanisms., Materials and Methods: phWRAP53-siRNA and pNeg-siRNA were constructed and transfected into Hep-2 cells with lipofectamine. Expression of WRAP53 was analyzed by RT-PCR and Western-blottin, radiosensitivity of Hep-2 cells was assessed colony formation assay, and the relative length of telomeres was measured by QPCR., Results: The data revealed that the plasmid of phWRAP53-siRNA was constructed successfully, and the mRNA and protein levels of WRAP53 were both obviously reduced in the Hep-2 cell line transfected with phWRAP53-siRNA. After Hep-2 cells were irradiated with X-rays, the D0 and SF2 were 2.481 and 0.472, respectively, in the phWRAP53-siRNA group, much lower than in the control group (D0 and SF2 of 3.213 and 0.592) (P<0.01). The relative telomere length in the phWRAP53-siRNA group was 0.185±0.01, much lower than in the untreated group (0.523±0.06) and the control group (0.435±0.01)., Conclusions: Decreasing the expression of WRAP53 using RNA interference technique can enhance the radiosensitivity of Hep-2 cell lines by influencing the telomere length. WRAP53 is expected to be a new target to regulate the radiosensitization of tumor cells.

Background: Parkinson disease (PD) is a common adult-onset neurodegenerative disorder, and PD related neuronal injury is associated with oxidative stress and mitochondrial dysfunction. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-oxidative and anti-apoptotic activities in in vitro and in vivo studies., Methods: The present study aimed to investigate the potential protective role of allicin in an in vitro PD model induced by 6-hydroxydopamine (6-OHDA) in PC12 cells. The protective effects were measured by cell viability, decreased lactate dehydrogenase (LDH) release and flow cytometry, and the anti-oxidative activity was determined by reactive oxygen species (ROS) generation, lipid peroxidation and the endogenous antioxidant enzyme activities. Mitochondrial function in PC12 cells was detected by mitochondrial membrane potential (MMP) collapse, cytochrome c release, mitochondrial ATP synthesis, and the mitochondrial Ca(2+) buffering capacity. To investigate the potential mechanism, we also measured the expression of mitochondrial biogenesis factors, mitochondrial morphological dynamic changes, as well as detected mitochondrial dynamic proteins by western blot., Results: We found that allicin treatment significant increased cell viability, and decreased LDH release and apoptotic cell death after 6-OHDA exposure. Allicin also inhibited ROS generation, reduced lipid peroxidation and preserved the endogenous antioxidant enzyme activities. These protective effects were associated with suppressed mitochondrial dysfunction, as evidenced by decreased MMP collapse and cytochrome c release, preserved mitochondrial ATP synthesis, and the promotion of mitochondrial Ca(2+) buffering capacity. In addition, allicin significantly enhanced mitochondrial biogenesis and prevented fragmentation of mitochondrial network after 6-OHDA treatment. The results of western blot analysis showed that the 6-OHDA induced decrease in the expression of optic atrophy type 1 (Opa-1), increase in mitochondrial fission 1 (Fis-1) and dynamin-related protein 1 (Drp-1) were all partially revised by allicin., Conclusion: In summary, our data strongly suggested that allicin treatment can exert protective effects against PD related neuronal injury through inhibiting oxidative stress and mitochondrial dysfunction with dynamic changes., (© 2015 S. Karger AG, Basel.)

Background: Increasing incidence rates of thyroid cancer have been noted worldwide, while the underlying reasons remain unclear., Methods: Using data from population-based cancer registries, we examined the time trends of thyroid cancer incidence in two largest cities in China, Shanghai and Hong Kong, during the periods 1973-2009 and 1983-2011, respectively. We further performed age-period-cohort analyses to address the possible underlying reasons for the observed temporal trends., Results: We observed continuous increases in the incidence rates of thyroid cancer in Shanghai and Hong Kong, since the 1980s, in addition to higher incidence rates in the 1970s in both sexes in Shanghai. The age-standardized incidence rate of thyroid cancer increased by 3.1% [95% confidence interval (CI): 1.0%, 5.1%] and 3.8% (95% CI: 1.9%, 5.7%) per year on average, respectively, in Shanghai men and women during the period 1973-2009, while it increased by 2.2% (95% CI: 1.5%, 2.8%) and 2.7% (1.6%, 3.8%) per year on average, respectively, in Hong Kong men and women during the period 1983-2011. We observed global changes in trends across all age groups in similar ways, in addition to varied trends across different generations (birth cohorts)., Conclusions: The increased incidence rates of thyroid cancer in these two Chinese populations during recent decades may be contributable to a combination of the introduction of more sensitive diagnostic techniques and the increasing prevalence of environmental exposures in the populations.

Purpose: To determine the effects of hypercholesterolemia in pregnant mice on the susceptibility to atherosclerosis in adult life through a new animal modeling approach., Methods: Male offspring from apoE-/- mice fed with regular (R) or high (H) cholesterol chow during pregnancy were randomly subjected to regular (Groups R-R and H-R, n = 10) or high cholesterol diet (Groups R-H and H-H, n = 10) for 14 weeks. Plasma lipid profiles were determined in all rats. The abdominal aorta was examined for the severity of atherosclerotic lesions in offspring., Results: Lipids significantly increased while high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol decreased in mothers fed high cholesterol chow after delivery compared with before pregnancy (p < 0.01). Groups R-H and H-R indicated dyslipidemia and significant atherosclerotic lesions. Group H-H demonstrated the highest lipids, lowest high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol, highest incidence (90%), plaque area to luminal area ratio (0.78 ± 0.02) and intima to media ratio (1.57 ± 0.05)., Conclusion: Hypercholesterolemia in pregnant mice may increase susceptibility to atherosclerosis in their adult offspring., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Melanoma has traditionally been viewed as a radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, radiotherapy may play a significant role in the treatment of melanoma. Previous studies have demonstrated that telomere length is a hallmark of radiosensitivity. The newly discovered mammalian CTC1‑STN1-TEN1 (CST) complex has been demonstrated to be an important telomere maintenance factor. In this study, by establishing a radiosensitive/radioresistant human melanoma cell model, MDA-MB-435/MDA-MB‑435R, we aimed to investigate the association of CTC1 expression with radiosensitivity in human melanoma cell lines, and to elucidate the possible underlying mechanisms. We found that CTC1 mRNA and protein levels were markedly increased in the MDA-MB‑435R cells compared with the MDA-MB‑435 cells. Moreover, the downregulation of CTC1 enhanced radiosensitivity, induced DNA damage and promoted telomere shortening and apoptosis in both cell lines. Taken together, our findings suggest that CTC1 increases the radioresistance of human melanoma cells by inhibiting telomere shortening and apoptosis. Thus, CTC1 may be an attractive target gene for the treatment of human melanoma.

We aimed to explore the association between aberrant DNA methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) and human mutL homolog 1 (hMLH1) genes with gastric cancer. A total of 283 gastric cancer patients who were confirmed by pathological diagnosis were included in our study. Aberrant DNA methylation of MGMT and hMLH1 were detected. The proportions of DNA hypermethylation in MGMT and hMLH1 in cancer tissues were significantly higher than those in remote normal-appearing tissues. The DNA hypermethylation of MGMT was correlated with the tumor-necrosis-metastasis stage in gastric cancer tissues. Results showed that individuals with gastric cancer in the N1 and M1 stages had a significantly higher risk of DNA hypermethylation of MGMT in cancer tissues [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.15-3.37 for the N1 stage; OR (95%CI) = 5.39 (2.08-14.98) for the M1 stage]. In conclusion, we found that aberrant hypermethylation of MGMT could be a predictive biomarker for detecting gastric cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality worldwide. Mitochondrial dysfunction has been postulated to render cancer cells resistant to apoptosis based on the Warburg hypothesis. However, few studies have investigated the prognostic value of mitochondrial DNA (mtDNA) content and G10398A polymorphism in NSCLC patients. mtDNA copy number and G10398A polymorphism in 128 NSCLC tissue samples were assessed by real-time PCR (RT-PCR) and PCR-RFLP respectively, and their relationship to prognosis were analyzed by survival analysis and Cox proportional hazards model. In vitro, an mtDNA deletion A549 ρ(0) cell model was utilized to assess the function of mtDNA on radiosensitivity. Cell cycle distribution and reactive oxygen species (ROS) were analyzed to elucidate the potential mechanisms. For the whole group, the median follow-up time and overall survival time were 22.5 and 23.4 months, respectively. Patients with high mtDNA content had a marginally longer survival time than patients with low mtDNA content (P=0.053). Moreover, patients with high mtDNA content plus 10398G had a significantly longer overall survival time compared with those having low mtDNA content plus 10398A (47 vs. 27 months, P<0.05). In addition, multivariate analysis showed that stage and low mtDNA content plus 10398A were the two most independent prognostic factors. In vitro, the A549 ρ(0) cells showed more resistance to radiation than ρ(+) cells. Following radiation, ρ(0) cells showed delayed G2 arrest and lower ROS level as compared to ρ(+) cells. In conclusion, the present study suggests that in patients with NSCLC, low mtDNA content plus 10398A could be a marker of poor prognosis which is associated with resistance to anticancer treatment caused by low mtDNA content plus 10398A polymorphism resulting in mitochondrial dysfunction.

Purpose: To evaluate the feasibility and efficacy of neoadjuvant chemotherapy involving docetaxel and cisplatin followed by intensity-modulated radiotherapy (IMRT) with concurrent cisplatin in patients with newly diagnosed stage III to IVB nasopharyngeal carcinoma (NPC)., Methods: Docetaxel (75 mg/m(2) on day 1) and cisplatin (75 mg/m(2) on day 1) were administered on a 3-week cycle for 2 courses, followed by radical IMRT (72 Gy/33F/6.5-7 W) with concurrent cisplatin (75 mg/m(2), on day 1) every 3 weeks for 2 cycles., Results: From June 2008 to October 2010, forty-six patients were recruited in this trial. Forty-five patients completed neoadjuvant setting, and all patients completed planned concurrent chemoradiotherapy (CCRT). The complete and partial response rates were 28.3 and 56.5 % after neoadjuvant chemotherapy, and 91.3, 8.7 % after CCRT, respectively. After median follow-up of 26 months (range 12-39 months), one patient experienced local recurrence and 4 patients developed distant metastasis. The 3-year overall survival and progression-free survival rate were 94.1 and 72.7 %, respectively. Neutropenia (37.0 %) and vomiting (28.3 %) were the most common Grade 3-4 adverse effects during neoadjuvant course, while mucositis (30.4 %), xerostomia (30.4 %) and radiodermatitis (21.7 %) were the most common Grades 3 acute toxicities during CCRT. Xerostomia (73.9 %), dysphagia (56.5 %), hear loss (30.4 %) and skin reaction (21.7 %) were the common Grade 1-2 late effects. There were no Grades 3-4 late toxicities., Conclusions: The protocol of neoadjuvant docetaxel and cisplatin followed by IMRT with concurrent cisplatin was well tolerated, with outstanding compliance and efficacy in locally advanced NPC, which deserved further follow-up.

Ku70/80 heterodimer is a central element in the nonhomologous end joining (NHEJ) DNA repair pathway, Ku80 playing a key role in regulating the multiple functions of Ku proteins. It has been found that the Ku80 protein located at telomeres is a major contributor to radiosensitivity in some telomerase positive human cancer cells. However, in ALT human osteosarcoma cells, the precise function in radiosensitivity and telomere maintenance is still unknown. The aim of this study was to investigate the effects of Ku80 depletion in the U2OS ALT cell line cell line. Suppression of Ku80 expression was performed using a vector-based shRNA and stable Ku80 knockdown in cells was verified by Western blotting. U2OS cells treated with shRNA-Ku80 showed lower radiobiological parameters (D0, Dq and SF2) in clonogenic assays. Furthermore, shRNA-Ku80 vector transfected cells displayed shortening of the telomere length and showed less expression of TRF2 protein. These results demonstrated that down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening.

This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study.

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R , by exposing the parental A549 cells to repeated γ-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

Among the components that make up a lateral-flow immunochromatographic assay (ICA), antibody is the key. In this paper, salbutamol (SAL) as a model analyte was meticulously designed to prepare immunogen and coating antigen in distinctly different ways. Four hybridoma cell lines were prepared and identified. Among them, C9 had highest affinity, best dose-response behavior, lowest limit of detection, and highest specificity and was chosen to be labeled with colloidal gold as the detector reagent and applied on the conjugate pad. Goat anti-mouse antibody and SAL-BSA conjugate were sprayed on a nitrocellulose membrane as test line and control line, respectively. Under the optimized conditions, the ICA strip was constructed based on a binding inhibition format. Color intensity on the test line was visually distinguishable from that of the negative sample within 5 min, with the visual detection limit of 1 ngml(-1) in phosphate-buffered saline. Cross-reactions with other β-agonists were not found (<1%). The results from ICA were in a good agreement with those obtained by enzyme-linked immunosorbent assay. The developed ICA has potential as a useful on-site screening tool for SAL in swine urine., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: To detect expression of (programmed death ligand 1, PD-L1)on CD14(+) Monocyte(Mo)in the patients with systemic lupus erythematosus(SLE)and their clinical significance is analyzed., Methods: The expression of PD-L1 on the CD14(+) Mo was examined in patients with 51 active SLE and 38 healthy controls(HC) by flow cytometry. The proportions of expression of PD-L1 on CD14(+) Mo were compared between not only inactive or active SLE patients and healthy controls(HC), but also between patients with lupus nephritis and without lupus nephritis. Correlation with clinical manifestations and laboratory findings was analyzed., Results: The Proportions of CD14(+) PD-L1(+) Mo were significantly increased in active and inactive SLE patients as compared with HC(all P<0.05). The proportions of CD14(+) PD-L1(+) Mo in SLE patients with nephritis were significantly higher than those in patients without nephritis. A positive correlation was observed for proportions of CD14(+) PD-L1(+) Mo with SLEDAI score, and amounts of proteinuria. Proportions of CD14(+) PD-L1(+) Mo in SLE patients with anti-dsDNA, anti-Sm, anti-U1RNP and anti-nucleosome were higher than those in SLE patients without those antibody(P<0.05)., Conclusion: The aberrations of proportions of CD14(+) PD-L1(+) Mo were observed in patients with SLE. Proportions of CD14(+) PD-L1(+) Mo were correlated with disease activity and production of antibody.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, and has a poor prognosis. In this study, we reported an exceptional clinical case of primary HCC with metastatic disease in the lungs 1 year following hepatic resection, and in the left adrenal gland 8 years following hepatic resection. Comprehensive treatments, including partial hepatic resection, systemic chemotherapies with various regimens, such as radiotherapy, were administered to this patient. In this case, there was no intrahepatic recurrence of the malignancy and the metastatic disease was sensitive to chemotherapy and radiotherapy. The patient remained alive and in good health for 10 years following the diagnosis of HCC despite early metastatic disease. This indicates that for certain patients with advanced stage HCC, palliative treatments may still be beneficial to their survival. We also discussed the advance in recent research into HCC treatment.

Aim: To investigate the expressions of Interleukin-17A receptor (IL-17AR) on the peripheral blood B lymphocytes of SLE patients and to analyze the correlations between IL-17AR and clinical parameters., Methods: Expression of IL-17AR on peripheral blood CD19(+);B lymphocytes were analyzed in 60 SLE patients and 33 healthy controls by flow cytometry. The difference of IL-17AR expression levels in two groups were compared. Furthermore, the correlation between IL-17AR expressions and clinical some measures, such as ESR, CRP, complement 3(C3), complement 4(C4), the amount of serum IgG, anti double strands DNA antibody, anti nuclear antibody, SLEDAI score and urine protein excretion were analyzed., Results: Compared with healthy subjects, the proportions of B cells expressing IL-17AR were higher among SLE patients. In SLE patients, groups with mouth ulcer, serositis, renal lesions or immunologic abnormality were higher than the negative groups separately. The positive correlations were observed between IL-17AR expression levels and clinical measure of the SLEDAI, CRP and serum triglyceride level. The negative correlation was observed between IL-17AR expression levels and clinical measure of the serum indirect bilirubin level, serum albumin level., Conclusion: Interleukin-17A receptor expression increased on peripheral blood B cells of SLE patients, and correlate with clinical measures.

To evaluate the relationship between pain and quality of life (QoL) in patients newly admitted to Wuhan Hospice Center, China. A total of 1,634 patients were analyzed in this retrospective study. A Numerical Rating Scale and Chinese-QoL instrument were used to assess pain score and QoL, respectively. Most patients experienced moderate to severe pain, which significantly impaired QoL. The pain was significantly correlated with appetite, mood, sleep, fatigue, pain intensity, daily activity, side effect, general appearance, and support from family. But there was no correlation with support from society, understanding of cancer, or attitude toward treatment. In our study, the relationship between pain and QoL was found to be reciprocal. The staff can offer a multidisciplinary care perspective for improving hospice care for this special group of population.

Objective: To evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) and to investigate the association of the status of KRAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome., Methods: Twenty-eight patients with advanced NSCLC were enrolled in this single center, uncontrolled pilot clinical study. All the patients developed drug resistance or disease progression after first-line chemotherapy of either a docetaxel + cisplatin regimen or a vinorelbine + cisplatin regimen and then received nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy. Eight cases were stage IIIB and 20 were stage IV. An i.v. dosage regimen of 200 mg of nimotuzumab was given as a single dose, injected into the patient at days 1, 8 and 15; i.v. gemcitabine was injected at a dose of 1000 mg/m 2 at days 1 and 8 and cisplatin (25 mg/m 2 i.v.) at days 1, 2 and 3. Each patient received four or more therapeutic cycles. The efficacy and toxic reactions were evaluated, as well as time to progression and overall survival., Results: In total, 28 patients with advanced NSCLC received 101 therapeutic cycles. The mean cycle number was 3.6. Median time to progression was 4.9 (2.5-6.5) months; median overall survival and 1-year survival rate were 9.8 months and 48.5%, respectively. There was one case of complete response, six cases of partial response, 11 cases of stable disease and 10 cases of progressive disease. Response rate was 25%, and clinical benefit rate was 64.3%. Major toxic reactions were bone marrow suppression and gastrointestinal reaction. Only one patient developed grade I acneiform eruption., Conclusion: Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced NSCLC was active and well-tolerated in this setting. Patients with EGFR amplification and KRAS gene wild type had a better prognosis. Prospective, randomized, controlled, large-scale clinical studies are needed to confirm the results., (© 2011 Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.)

In this study we investigated the potential effects of Angelica sinensis on the growth and metastasis in human lung adenocarcinoma A549 cells. In vitro the Cck-8 assays showed that Angelica sinensis had weak antiproliferative effect on A549 cells only at high concentration. The cell adhesion assay showed that Angelica sinensis decreased the adhesive ability of A549 cells in a dose- and time-dependent manner. Transwell invasion and migration assay showed that Angelica sinensis reduced the invasive and migratory abilities of A549 cells in a dose-dependent manner. In vivo the animal experiments showed that Angelica sinensis suppressed lung metastasis of nude mice at high concentration. Then, we attempted to clarify the mechanisms of anti-metastatic activities of Angelica sinensis. The results showed Angelica sinensis inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), it involved the down-regulation of the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels, which may be associated with Angelica sinensis suppressing the expression of TGF-β1. It also involved the increase of the tissue inhibitors of metalloproteinases TIMP-2, but TIMP-1 decreased upon incubation of A549 cells with Angelica sinensis. The results suggest that Angelica sinensis might exert anti-growth and anti-metastasis activity against lung cancer cells through the decrease of MMP-2, MMP-9, TGF-β1 and TIMP-1 and increase of TIMP-2.

Background: Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation-inducible sequence CC(A/T)(6) GG (known as CArG elements)., Methods: Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo., Results: The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer-specific characteristics. The chimeric promoter was better at driving radiation-inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter-mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice., Conclusions: The current results indicated that a combinational cancer-specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment., (Copyright © 2011 American Cancer Society.)

Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p<0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The basic helix-loop-helix (bHLH) transcription factors (TFs) comprise one of the largest families of TFs involved in developmental and physiological processes in plants. Here, we describe the functional characterization of two bHLH TFs (NtAn1a and NtAn1b) isolated from tobacco (Nicotiana tabacum) flowers. NtAn1a and NtAn1b originate from two ancestors of tobacco, N. sylvestris and N. tomentosiformis, respectively. NtAn1a and NtAn1b share high sequence similarity with other known flavonoid-related bHLH TFs and are predominantly expressed in flowers. GUS expression driven by the NtAn1a promoter is consistent with NtAn1 transcript profile in tobacco flowers. Both NtAn1a and NtAn1b are transcriptional activators as demonstrated by transactivation assays using yeast cells and tobacco protoplasts. Ectopic expression of NtAn1a or NtAn1b enhances anthocyanin accumulation in tobacco flowers. In transgenic tobacco expressing NtAn1a or NtAn1b, both subsets of early and late flavonoid pathway genes were up-regulated. Yeast two-hybrid assays showed that NtAn1 proteins interact with the previously characterized R2R3-MYB TF, NtAn2. The NtAn1-NtAn2 complex activated the promoters of two key anthocyanin pathway genes, dihydroflavonol reductase and chalcone synthase. The promoter activation is severely repressed by dominant repressive forms of either NtAn1a or NtAn2, created by fusing the SRDX repressor domain to the TFs. Our results show that NtAn1 and NtAn2 act in concert to regulate the anthocyanin pathway in tobacco flowers and NtAn2 up-regulates NtAn1 gene expression.

Pulmonary fibrosis is a common delayed side effect of radiation therapy. Since its mechanism is almost unknown, little can be done to prevent or treat it. Th2 cytokines have been clearly implicated as mediators of asthma, and evidence is mounting that type 2 immune responses may also promote the development of pulmonary fibrosis. The aim of this study was to investigate whether Th2-like immune responses account for the development and progression of chronic radiation pulmonary fibrosis. C57BL/6 mice received thoracic irradiation of 12 Gy and were sacrificed at 1 h and 1, 2, 4, 8, 16 and 24 weeks post-irradiation (p.i.). We assayed the expression of IL-13 in serum, and the expression of hydroxyproline and the mRNA and protein of GATA-3 and Arg-1 in lung tissue. mRNA and protein analysis revealed the expression of these Th2-immune response-associated factors (GATA-3, IL-13 and Arg-1) in mice after irradiation. Without causing conspicuous fibrotic pathological changes at the early post-irradiation phase (1 and 2 weeks p.i.), a Th2 profile was confirmed by significantly elevated expression of Th2-specific transcription factor GATA-3 mRNA (P<0.01). Protein analysis confirmed the GATA-3 mRNA expression. Following significantly elevated expression of hydroxyproline (P<0.01) at 16 weeks p.i., IL-13 and Arg-1 expression reached maximal values in serum and lung tissue and maintained high levels up to 24 weeks p.i., respectively (P<0.01). Our data indicate that lung irradiation induces Th2 polarization. Furthermore, Th2-like immune response may take part in radiation-induced pulmonary fibrosis (RILF), and GATA-3 may play an important role in promoting RILF. Thus, GATA-3 may be an important target for the treatment of RILF.

Objective: To investigate the relationship between 22q11 microdeletion syndrome and congenital heart disease., Methods: Clinical screening assessment and genetic testing using standard fluorescence in-situ hybridization (FISH) were applied in 207 subjects suspected for 22q11 microdeletion syndrome. Patients with 22q11 microdeletion syndrome were examined by echocardiography, patients with complicated congenital heart disease were examined further by cardiac catheterization., Results: 22q11 microdeletion syndrome was detected in 39 subjects. The incidence of 22q11 microdeletion syndrome was 1.6% in suspects with simple congenital heart disease without extracardiac manifestations, 53.0% in suspects with congenital heart disease combined with at least two extracardiac manifestations, 3.8% in suspects without congenital heart disease. The incidence of congenital heart disease in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 94.9% and 54.2% (P < 0.01). The incidence of congenital heart disease combined with at least two extracardiac manifestations in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 89.7% and 18.5% (P < 0.01). In 22q11 microdeletion syndrome patients, Tetralogy of Fallot was the most common type of congenital heart disease. Dysmorphic faces, learning difficulties and retarded physical development were the most common extracardiac manifestations of the congenital heart disease patients., Conclusion: 22q11 microdeletion syndrome is related to congenital heart disease.

Background: The purpose of this study was to investigate the potential role of variable microRNA (miRNA) expression in the development of multidrug resistance (MDR) in head and neck cancer., Methods: Head and neck squamous cell carcinoma cell lines UMSCC-1 and SQ20B were treated with docetaxel at increasing concentrations to develop resistant cell lines. Parental and resistant cells were treated with cisplatin, 5-fluorouracil, paclitaxel, methotrexate, and doxorubicin to confirm cross-resistance. The miRNA pattern of resistant cells was then compared with their parental cells., Results: Docetaxel treatment successfully induced resistance primarily and induced multidrug cross-resistance. Resistant cells showed significant downregulation of miR-100, miR-130a, and miR-197 and upregulation in miR-101, miR-181b, miR-181d, and miR-195 expression when compared with their parent cells (p < .01). Real-time polymerase chain reaction (PCR) analysis confirmed statistically significant downregulation in miR-100 and miR-130a and upregulation in miR-181d expression (p < .001)., Conclusion: Alterations in miRNA expression has direct relationship to MDR in head and neck cancer and may serve as biomolecular targets for reversal of MDR., (Copyright © 2010 Wiley Periodicals, Inc.)

To identify genes induced during Pseudoperonospora cubensis (Berk. and Curk.) Rostov. infection in cucumber (Cucumis sativus L.), the suppression subtractive hybridization (SSH) was performed using mixed cDNAs prepared from cucumber seedlings inoculated with the pathogen as a tester and cDNA from uninfected cucumber seedlings as a driver. A forward subtractive cDNA library (FSL) and a reverse subtractive cDNA library (RSL) were constructed, from which 1,416 and 1,128 recombinant clones were isolated, respectively. Differential screening of the preferentially expressed recombinant clones identified 58 unique expressed sequence tags (ESTs) from FSL and 29 from RSL. The ESTs with significant protein homology were sorted into 13 functional categories involved in nearly the whole process of plant defense such as signal transduction and cell defense, transcription, cell cycle and DNA processing, protein synthesis, protein fate, proteins with binding functions, transport, metabolism and energy. The expressions of twenty-five ESTs by real-time quantitative RT-PCR confirmed that differential gene regulation occurred during P. cubensis infection and inferred that higher and earlier expression of transcription factors and signal transduction associated genes together with ubiquitin/proteasome and polyamine biosynthesis pathways may contribute to the defense response of cucumber to P. cubensis infection. The transcription profiling of selected down-regulated genes revealed that suppression of the genes in reactive oxygen species scavenging system and photosynthesis pathway may inhibit disease development in the host tissue.

Objective: To evaluate the efficacy and safety of two insulin treatment protocols using a continuous glucose monitoring system., Methods: Type 2 diabetic patients mellitus with unsatisfactory control of fasting blood glucose by oral antidiabetic drugs were included in the study. The patients were randomized into two groups to receive bedtime injection of glargine and oral antidiabetic drugs (group A) or injection of Novolin 30 R twice a day (group B) for 12 weeks. The insuline dose was adjusted according to fasting blood glucose till discharge. Continuous glucose monitoring system was used to record the average blood glucose, fasting blood glucose, 2 h postprandial blood glucose, AUCPG ≥ 10.0 mmol/L%, HbA1c and C peptide, bedtime blood glucose, 3:00 AM blood glucose, the incidence of hypoglycemia and body mass index., Results: The average blood glucose, fasting blood glucose, 2 h postprandial blood glucose, AUCPG ≥ 10.0 mmol/L% and HbA1c was significantly decreased and C peptide significantly increased in the two groups after the treatments. The patients in glargine group showed better improvement with a significantly lower incidence of hypoglycemia than those in Novolin 30 R group. BMI underwent no significant changes in the two groups after the treatments., Conclusion: Glargine therapy better mimics the physiological insulin secretion patterns, and when combined with oral antidiabetic drugs, can be more effective and safer than premixed insulin.

Attention is a complex domain that has reawakened research interest in recent years. There are relatively few studies that have examined age-related changes across different attention subcomponents, such as selection, maintenance, and control, using large samples covering a wide age range. The present study assessed performance in 466 participants in order to identify the ages at which mature performance was reached across differing attention subcomponents. Furthermore, we investigated whether the nature of the attentional demands or task difficulty predicted the age at which stable levels of performance were reached. The results supported the former rather than the latter alternative.

To achieve a more complete understanding of the molecular mechanisms underlying tumor radioresistance, we established a radioresistant cell line from the human larynx squamous cell carcinoma cell line Hep-2 after long-term radiation induction. The biological features of the resulting cell lines were characterized. cDNA microarray technology was used to measure the alterations of gene expression in the radioresistant cells. We found that certain genes associated with DNA repair, cell cycle, apoptosis, etc. were significantly changed. In particular, genes related to telomeres, such as POT1, were significantly altered. Radioresistant cells had higher telomerase activity and longer telomeres than their parental cells. Our research suggests that telomere function is a novel hallmark of cellular radiosensitivity, and the mechanistic link between telomere maintenance and radiosensitivity may involve the genes and pathways we implicated in this study.

Background: There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients., Methods: MBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy., Results: The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%)., Conclusions: Capecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.

Objective: To identify the prevalence and risk factors of diabetes and prediabetes in the community residents above 18 years old in the suburbs of Guangzhou., Methods: Between April and May in 2008, the residents above 18 years living in 6 communities of Guangzhou for 5 or more years were sampled with multistage clustering sampling. The sampled residents were surveyed by questionnaires, and physical examination and glucose determination were carried out., Results: A total of 1532 residents were sampled. The incidence of diabetes mellitus in these community residents was 8.46%, and that of impaired glucose regulation was 6.59%. Age, body mass index, family history of diabetes mellitus, case history of hypertension, hyperlipidemia, hypertension and smoking were all the independent risk factors for impaired glucose regulation and diabetes mellitus., Conclusion: Diabetes and prediabetes are prevalent in the community residents in Guangzhou. Controlling the risk factors such as obesity, hypertension, lipid metabolism disorder among the residents above 40 years with a family history of diabetes mellitus and hypertension is key to prevention of impaired glucose regulation and diabetes mellitus.

Many TFIIIA-type zinc finger proteins (ZFPs) play important roles in stress responses in plants. In the present study, a novel zinc finger protein gene, StZFP1, was cloned from potato. StZFP1 is a typical TFIIIA-type two-finger zinc finger gene with one B-box domain, one L-box domain and a DLN-box/EAR motif. The StZFP1 genes belong to a small gene family with an estimated copy number of four or five, located on chromosome I. StZFP1 is constitutively expressed in leaves, stems, roots, tubers and flowers of adult plants. Expression of StZFP1 can be induced by salt, dehydration and exogenously applied ABA. StZFP1 expression is also responsive to infection by the late blight pathogen Phytophthora infestans. Transient expression analysis of StZFP1:GFP fusion protein revealed that StZFP1 is preferentially localised in the nucleus. Ectopic expression of StZFP1, driven by the Arabidopsis rd29A promoter in transgenic tobacco, increased plant tolerance to salt stress. These results demonstrate that StZFP1 might be involved in potato responses to salt and dehydration stresses through an ABA-dependent pathway.

Rice-based diets may have been reported to protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of rice-based diet was addressed using the apolipoprotein E knockout (apoE-/-) mice fed rice protein isolate (RPI) or casein (CAS). Reduced atherosclerotic lesions were observed in aortic sinus and enface analyses of the descending aorta in RPI-fed apoE-/- mice compared with CAS-fed mice. Plasma total- and HDL-cholesterol levels were not different amongst the two groups, suggesting alternative mechanism(s) could have contributed to the atheroprotective effect of rice-based diets. Plasma oxLDL and anti-oxLDL IgG levels were significantly decreased in RPI-fed compared to CAS-fed animals. Plasma and aortic tissue GSH levels and GSH:GSSG ratio were higher in RPI-fed mice compared to CAS-fed group. Interestingly, RPI feeding increased mRNA and protein expression of superoxide dismutase, and mRNA expression of catalase, glutathione peroxidase and glutathione reductase, key antioxidant enzymes implicated inhibiting oxidative stress leading to atherosclerosis. In conclusion, these findings suggest that the reduction in atherosclerotic lesions observed in mice fed the rice-based diet is mediated in part by inhibiting oxidative stress and subsequent oxLDL generation that could result in reduced foam cell formation, an early event during atherogenesis.

Radiation-induced pulmonary injury is a severe complication affecting the quality of life of patients. Although the pathophysiology of the process is not fully understood, we hypothesized that it is potentially related to macrophages and their secretion of matrix metalloproteinase-9 (MMP-9). Macrophages are a type of inflammatory cell that synthesize hundreds of bioactive substances and enzymes. MMP-9 is closely involved in the maintenance of the basilar membrane, and leads to increased extracellular matrix deposition within the lung, which is a characteristic feature of radiation-induced lung fibrosis. We examined the role of ionizing radiation in modulating the production of MMP-9 in a macrophage cell line. RAW264.7 cells were irradiated with various doses of γ-rays, and then MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined at several time points. RT-PCR revealed a marked increase in the levels of MMP-9 mRNA, which peaked at 24 h post-irradiation and had begun to decline by 48 h. By contrast, TIMP-1 mRNA experienced only a slight increase at 24 h post-irradiation, reaching significance at 48 h post-irradiation. Western blot analysis demonstrated an increased expression of MMP-9 protein in the irradiated cells, while TIMP-1 protein levels were not notably changed. Dexamethasone inhibited the increased expression of MMP-9 protein induced by ionizing radiation. These results indicate that MMP-9 expression by RAW264.7 cells, and an imbalance between MMP-9 and TIMP-1, may be involved in radiation-induced lung injury.

Objective: To investigate the relationship between the dosage of irbesartan and the renal tissue structure in diabetic rats., Methods: Male Wistar rats was given a single intraperitoneal dose (mg/kg) of streptozotocin to induce diabetes. The diabetic rats were randomized into 4 groups and received 4 weeks later 25 mg/kg (n=9), 50 mg/kg (n=9), 200 mg/kg (n=9) irbesartan intragastrically, or equal volume of water (model group, n=11) on a daily basis. Seven normal rats receiving with equal volume of water served as the normal control. All the rats were sacrificed after 8 weeks and the 24-hour albumin excretion, renal mass index and the volume of the glomerulus were measured., Results: The 24-hour albumin excretion, renal mass index and volume of the glomerulus in the 3 irbesartan groups were significantly decreased as compare with those in the model group; the reductions in 50 and 200 mg/kg irbesartan groups were significant greater than those in 25 mg/kg irbesartan group., Conclusion: Irbesartan can decrease the 24-hour urinary albumin excretion and relive glomerulopathy in diabetic rats. Within a certain dose range, irbesartan produces a dose-dependent protective effect on the renal structures in the diabetic rats.

Tobacco is a commonly used heterologous system for studying combinatorial regulation of the flavonoid biosynthetic pathway by the bHLH-MYB transcription factor (TF) complex in plants. However, little is known about the endogenous tobacco bHLH and MYB TFs involved in the pathway. Ectopic expression in tobacco of heterologous bHLH TF genes, such as maize Lc, leads to increased anthocyanin production in the reproductive tissues, suggesting the presence of a reproductive tissue-specific MYB TF that interacts with the Lc-like bHLH TFs. We isolated a gene (NtAn2) encoding a R2R3 MYB TF from developing tobacco flowers. NtAn2 shares high sequence homology with other known flavonoid-related MYB TFs and is mostly expressed in developing flowers. Constitutive ectopic expression of NtAn2 induces whole-plant anthocyanin production in tobacco and Arabidopsis. In transgenic tobacco and Arabidopsis expressing NtAn2, both subsets of early and late flavonoid pathway genes are up-regulated. Suppression of NtAn2 by RNAi in tobacco resulted in a white-flowered phenotype and the inhibition of the late pathway genes. Yeast two-hybrid assays demonstrated that NtAn2 can interact with five heterologous bHLH TFs known to induce anthocyanin synthesis in other species including maize, perilla, snapdragon and Arabidopsis. Bimolecular fluorescent complementation using split YFP demonstrated that NtAn2 interacts with Lc in tobacco cells and that the complex is localized to nuclei. Transient co-expression of NtAn2 and Lc or Arabidopsis TT8 in tobacco protoplasts activated the promoters of two key flavonoid pathway genes, chalcone synthase and dihydroflavonol reductase. These results suggest that NtAn2 is a key gene controlling anthocyanin production in reproductive tissues of tobacco.

Human telomerase reverse transcriptase (hTERT) promoter has been proposed in cancer-targeted gene therapy. However, this promoter has not been strong enough to achieve therapeutic levels of transgene expression. We favor the hypothesis that telomerase may participate in the process of DNA repair and that the up-regulation of hTERT promoter activity may be a reaction to DNA damage. In previous investigations, we tested an 'indirected-activator' strategy that utilizes radiation to increase the activity of the hTERT promoter. The purpose of the present study was to implement a strategy using cisplatin to enhance hTERT promoter activity. The results indicate that, in human uterine cervical cancer (HeLa) cells exposed to 5 µg/ml cisplatin, the hTERT promoter had 3.1-fold increased activity compared to untreated cells. In addition, the combination of cisplatin and hTERT promoter-mediated horseradish peroxidase/indole-3-acetic acid gene-directed enzyme prodrug therapy induced cell cycle arrest at the S phase and apoptosis leading to a more significant reduction in cell viability. These findings suggest that hTERT promoter-mediated gene therapy is improved when combined with cisplatin.

Background: New materials and devices have been used in the management of cardiac malformations. In this paper, we present our experience with interventional occlusion of congenital vascular malformations., Methods: Between January 1997 and December 2005, 139 patients with congenital vascular malformations who had undergone interventional occlusion in the Children's Hospital, Zhejiang University School of Medicine were studied. The clinical data of the patients were retrospectively reviewed including pre-operative evaluation, surgical procedures, immediate complete closure rate, short-term complications, and short-term outcome., Results: Of the 139 patients, 126 had patent ductus arteriosus, and successful deployment was achieved in 121 of the 126 patients (96%, 121/126). Six patients had coronary artery fistula and 14 different coils were used for embolization; the immediate complete closure rate was 83.3%, and the complete closure rate after one month was 100%. The abnormal vessels of 3 patients with pulmonary sequestration were completely occluded using four 0.038-inch Gianturco coils. In 3 patients with aortopulmonary collaterals, 14 abnormal vessel branches were occluded with sixteen 0.038-inch Gianturco coils, reaching a closure rate of 100%. One patient with pulmonary arteriovenous fistula was occluded successfully with two 0.038-inch Gianturco coils., Conclusions: Transcatheter closure using coils is a safe and effective alternative to surgical ligation in the management of congenital vascular malformations in children. Selection of appropriate coils is important to achieve a better outcome.

Radiosensitization of cancer cells to irradiation could improve the efficacy of radiotherapy. The early transcriptional factor (Egr-1) promoter induced expression of downstream genes after irradiation. TNF-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in malignant cells, but displayed little or no toxicity on normal cells. In this study, we constructed pcDNA3.1-Egr-1-TRAIL (pEgr.1-TRAIL) recombinant plasmid and evaluated its effect on human colon cancer cell line SW480. pEgr.1-TRAIL transfection combined with radiotherapy caused dramatically elevation of TRAIL expression both in mRNA and protein levels, much lower radiobiological parameters in clonogenic assays, accompanied by remarkably increase in apoptosis ratio. Furthermore, pEgr.1-TRAIL transfected cells displayed higher proportion in G0/G1 phase. Our results suggested that pEgr.1-TRAIL can sensitize SW480 cells to radiation, and the radiosensitization is related to cell cycle changes and apoptosis mediated by up-regulation of TRAIL expression. These findings support the potential future application of genetic radiotherapy against carcinoma.

Purpose: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type., Methods and Materials: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone., Results: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels., Conclusions: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.

Telomere-associated proteins function as survival factors in telomere maintenance, which are major contributors to radiosensitivity in human cancers. The aim of this study was to investigate the association of telomere-associated gene expression and radiation resistance in human larynx squamous carcinoma. The changes of telomere-associated gene expressions and bionomical characteristics that occur in two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R), with different radiosensitivities in vitro were explored in the present study. Based on previous research, elevated POT1 and TPP1 expressions were detected by reverse transcription-PCR and Western blotting in Hep-2R cell lines. Furthermore, Hep-2R cells showed increased recovery ratio accompanied by a reduction of cell arrested in G2/S phase, suggesting that the radioresistance of Hep-2R cells was due to a faster growth in which telomere length had recently been demonstrated to be a powerful prognostic marker. These results manifest that radioresistant Hep-2R cell lines showed certain changes in gene expression and bionomical profiles that are different from the profile changes of the more-sensitive Hep-2 cell lines, and that evaluation of telomere-associated genes may be a prognostic marker for response to radiotherapy in larynx squamous cell carcinoma (LSCC).

Purpose: Functional MR imaging of the human cervical spinal cord was carried out on volunteers during alternated rest and a complex finger tapping task, in order to detect image intensity changes arising from neuronal activity., Methods: Functional MR imaging data using single-shot fast spin-echo sequence (SSFSE) with echo time 42.4 ms on a 1.5 T GE Clinical System were acquired in eight subjects performing a complex finger tapping task. Cervical spinal cord activation was measured both in the sagittal and transverse imaging planes. Postprocessing was performed by AFNI (Analysis of Functional Neuroimages) software system., Results: Intensity changes (5.5-7.6%) were correlated with the time course of stimulation and were consistently detected in both sagittal and transverse imaging planes of the cervical spinal cord. The activated regions localized to the ipsilateral side of the spinal cord in agreement with the neural anatomy., Conclusion: Functional MR imaging signals can be reliably detected with finger tapping activity in the human cervical spinal cord using a SSFSE sequence with 42.4 ms echo time. The anatomic location of neural activity correlates with the muscles used in the finger tapping task.

TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining. Radionsensitivity of Hep-2R cells treated with TRA-8 were investigated with long-term clonogenic assays. Regulation of DR5 expression in cells after radiation was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. The results suggested that TRA-8 enhanced radionsensitivity of Hep-2R cells, and that TRA-8 regulated Hep-2R cell cycle arrest at G2/M phase. Irradiation up-regulated the expression of DR5, and when combined with TRA-8 yielded optimal survival benefit. Therefore, TRA-8 can be used in combination with irradiation in radioresistant human larynx squamous carcinoma cells. Monoclonal antibodies such as TRA-8 may play an important role in the development of an effective treatment strategy for patients with radioresistant cancers.

Objective: To explore the therapeutic efficiency of human telomerase reverse transcriptase promoter (hTERTp) mediated horseradish peroxidase (HRP) catalyzed effects of indole-3-acetic (IAA) on laryngeal squamous cell carcinoma with different radiosensitivity in vivo., Methods: Human laryngeal squamous cell carcinoma Hep-2 and Hep-2R cells were transplanted into nude mice. After growing to about 30 approximately 50 mm3, the tumor-bearing mice were randomly divided into eight groups: Hep-2 line: combined group (A), gene group (B), radiation group (C) and blank group (D); Hep-2R line: combined group (AR), gene group (BR), radiation group (CR) and blank group (DR). The phTERTp-HRP was delivered by intratumoral injection and the IAA by intraperitoneal injection, combined with 2 Gy daily radiation to a total dose of 30 Gy. The tumor volume was recorded. The cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The expression of HRP protein was detected by AP immunohistochemisty., Results: The tumor growth of combined groups was attenuated significantly and the tumor volume of Hep-2R blank group was the largest. The inhibition rate of each group was: A: 54.8%, B: 10.0%, C: 31.9%; AR: 52.7%, BR: 24.8%, CR: 17.0%. In the combined groups, necrosis and apoptosis of tumor cells were observed under the light microscope and the apoptotic index [A (16.6 +/- 1.3)% vs. AR (17.6 +/- 1.3)%] of tumor cells was highest (P < 0.05). The HRP protein expression of BR (33.3 +/- 8.9)% was higher than that of B (21.9 +/- 5.7)%, which was directly up-regulated in the tumors (45.0% vs. 54.8%, P < 0.05) after radiation., Conclusion: In the Hep-2- and Hep-2R-transplantation tumors in nude mice, hTERTp can be induced by radiation and enhance the expression of horseradish peroxidase (HRP) gene according to telomerase activity. hTERTp-HRP/IAA system, which has synergistic effects with radiation and inhibits the tumor growth by induction of apoptosis and necrosis, may be a new gene-radiation strategy for the treatment of laryngeal carcinoma.