Current Issue : January - March Volume : 2012 Issue Number : 1 Articles : 6 Articles
Background: Most skin cancers are preventable by encouraging consistent use of sun protective behaviour. In\r\nAustralia, adolescents have high levels of knowledge and awareness of the risks of skin cancer but exhibit\r\nsignificantly lower sun protection behaviours than adults. There is limited research aimed at understanding why\r\npeople do or do not engage in sun protective behaviour, and an associated absence of theory-based interventions\r\nto improve sun safe behaviour. This paper presents the study protocol for a school-based intervention which aims\r\nto improve the sun safe behaviour of adolescents.\r\nMethods/design: Approximately 400 adolescents (aged 12-17 years) will be recruited through Queensland,\r\nAustralia public and private schools and randomized to the intervention (n = 200) or ââ?¬Ë?wait-listââ?¬â?¢ control group (n =\r\n200). The intervention focuses on encouraging supportive sun protective attitudes and beliefs, fostering\r\nperceptions of normative support for sun protection behaviour, and increasing perceptions of control/self-efficacy\r\nover using sun protection. It will be delivered during three Ã?â?? one hour sessions over a three week period from a\r\ntrained facilitator during class time. Data will be collected one week pre-intervention (Time 1), and at one week\r\n(Time 2) and four weeks (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun\r\nprotection behaviour. Secondary outcomes include attitudes toward performing sun protective behaviours (i.e.,\r\nattitudes), perceptions of normative support to sun protect (i.e., subjective norms, group norms, and image norms),\r\nand perceived control over performing sun protective behaviours (i.e., perceived behavioural control).\r\nDiscussion: The study will provide valuable information about the effectiveness of the intervention in improving\r\nthe sun protective behaviour of adolescents....
Background: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal\r\ntype B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small\r\npseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1\r\n(HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells\r\ncultured as 3-D spheroids, which morphologically simulate IMPC cell clusters.\r\nMethods: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers.\r\nBinding of HIF-1a to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by\r\nChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric\r\nassay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay.\r\nResults: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of\r\nMDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was\r\nincreased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than\r\nMCF7 cells cultured as monolayer. Finally, HIF-1a inhibition either by incubating cells with 3-(5�-hydroxymethyl-2�-\r\nfuryl)-1-benzylindazole (a widely used HIF-1a inhibitor) or by transfecting cells with specific siRNA for HIF-1a\r\nsignificantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin\r\naccumulation in MCF7 3-D spheroids.\r\nConclusions: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is\r\nassociated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same\r\nmechanism may be suggested for IMPC drug resistance....
Background: An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed.\r\nTherefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG\r\nexpression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R,\r\nFSH-R) expression and survival in ovarian cancer patients.\r\nMethods: Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient\r\ncharacteristics, histology including histological subtype, tumor stage, grading and follow-up data were available.\r\nSerum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined\r\nby immunohistochemistry.\r\nResults: HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian\r\ntumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared\r\nto benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified\r\nsignificant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the\r\nhistological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO\r\nstage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but\r\nnot to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer\r\npatient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG\r\npositive tumors (hCG positive 75.0% vs. hCG negative 50.5%).\r\nConclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG\r\nis often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression\r\ncorrelates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic\r\nvalue. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies....
Background: Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for\r\ncolorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are\r\nneeded for the individual management of those patients undergoing SIRT.\r\nMethods: Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with\r\nextensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of\r\nnucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly\r\ndetermined 3 months after therapy and with overall survival.\r\nResults: Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), Creactive\r\nprotein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA\r\n21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well\r\nas 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35)\r\nthan in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST,\r\ncholine esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and\r\nnucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-\r\nRegression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h\r\nvalues were additionally included, nucleosomes (24 h) further improved the existing model.\r\nConclusion: Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for\r\nSIR-therapy and to early estimate the response to SIR-therapy....
Background: The association between the TERT rs2736100 single nucleotide polymorphism (SNP) and cancer risk\r\nhas been studied by many researchers, but the results remain inconclusive. To further explore this association, we\r\nperformed a meta-analysis.\r\nMethods: A computerized search of PubMed and Embase database for publications on the TERT rs2736100\r\npolymorphism and cancer risk was performed and the genotype data were analyzed in a meta-analysis. Odds\r\nratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of\r\nheterogeneity, cumulative meta-analysis and assessment of bias were performed in our meta-analysis.\r\nResults: A significant association between the TERT rs2736100 polymorphism and cancer susceptibility was revealed\r\nby the results of the meta-analysis of the 25 case-control studies (GG versus TT: OR = 1.72, 95% CI: 1.58, 1.88; GT\r\nversus TT: OR = 1.38, 95% CI: 1.29, 1.47; dominant model-TG + GG versus TT: OR = 1.47, 95% CI: 1.37, 1.58; recessive\r\nmodel-GG versus TT + TG: OR = 1.37, 95% CI 1.31, 1.43; additive model-2GG + TG versus 2TT + TG: OR = 1.30, 95%\r\nCI: 1.25, 1.36). Moreover, increased cancer risk in all genetic models was found after stratification of the SNP data\r\nby cancer type, ethnicity and source of controls.\r\nConclusions: In all genetic models, the association between the TERT rs2736100 polymorphism and cancer risk was\r\nsignificant. This meta-analysis suggests that the TERT rs2736100 polymorphism may be a risk factor for cancer.\r\nFurther functional studies between this polymorphism and cancer risk are warranted....
Background: In this study several tumor-related volumes were assessed by means of a computer-based\r\napplication and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative\r\nvolumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase)\r\nrelated parameters were compared with those of volumetry in order to observe possible relevance of this molecule\r\nin tumor development.\r\nMethods: We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy\r\nwith concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance\r\n(MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes\r\nmeasured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on\r\npostoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also\r\nincluded in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligationdependent\r\nProbe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with\r\nimmunohistochemistry in a total of 44 cases with available histologic material.\r\nResults: In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor\r\non the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030).\r\nFurthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter\r\nmethylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13\r\nmethylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely\r\nassociated with pre-operative tumor necrosis (p = 0.021).\r\nConclusions: Our findings implicate that volumetric parameters may have a significant role in the prognosis of\r\nGBM patients. Furthermore, volumetry could help not only to improve the prediction of outcome but also the\r\noutcome itself by identifying patients at high risk of treatment failure and, thus, seek alternative treatment for these\r\npatients. In this small series, MGMT protein was associated with less aggressive tumor characteristics....
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