1,720,977 research outputs found

    Anti-oestrogen therapy in the treatment of desmoid tumours. A systematic review

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    Abstract AIM: The treatment of desmoid tumours (DTs) is controversial. Anti-oestrogen therapy has frequently been used, but clear information of its efficacy is lacking. In this systematic review we have undertaken a comprehensive analysis to assess the effectiveness of anti-oestrogen therapy in terms of ability to induce partial or complete regression of DTs. METHOD: A systematic review of articles published in English between January 1983 and December 2009 was carried out according to the RECIST criteria. A literature search was performed on electronic databases including: United States National Library of Medicine (MEDLINE-PubMed), Excerpta Medica (EMBASE), Cochrane Library and Google search engine. Two-hundred articles dealing with DTs were identified but only fourty-one were were selected as appropriate for the study. The chi-square test was used for statistical analysis. RESULTS: Data on 168 DTs treated with anti-oestrogen agents, alone or in combination with nonsteroidal anti-inflammatory drugs, were identified with an overall response rate of 51%. There was no difference in response according to the type of DTs or between different anti-oestrogen therapies. Combination with anti-inflammatory drugs did not improve the outcome. Toremifene was sometimes effective in cases resistant to tamoxifen. Response did not seem to be related to oestrogen receptor status. CONCLUSIONS: Despite potential inaccuracies in the methodology, the results of the review indicate that anti-oestrogen therapy produces some effect in about one half of patients with DTs. Its indication compared with other treatments is discussed

    Lipoprotein(a), lipids and proinflammatory cytokines in patients undergoing major abdominal surgery

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    Background: The aims were to investigate whether surgical stress can induce a positive or negative lipoprotein(a) acute response, to determine any association with apolipoprotein(a) phenotypes, and to establish whether any such response is dependent on changes in lipids and proinflammatory cytokines. In addition, the impact of interleukin (IL) 6 genetic variability on the cytokine response to surgery was examined. Methods: This prospective, observational study included 41 patients with cancer referred for abdominal surgery. Preoperative (T0) plasma concentrations of lipoprotein(a), IL-6, tumour necrosis factor α, and serum concentrations of transforming growth factor β1 and lipids, were compared with values obtained 5 h (T1), 24 h (T2) and 5 days (T3) after surgery. Apolipoprotein(a) Kringle IV (KIV)-VNTR (variable-number tandem repeat) and IL-6 −174 G/C polymorphisms were analysed. Results: Lipoprotein(a) was found to act as a negative acute-phase reactant (30·0 per cent reduction at T2) (P = 0·009). Surgery had a more profound impact on subjects with low KIV-VNTR. After surgery, lipoprotein(a) correlated significantly with corrected low-density lipoprotein (LDL)-cholesterol (r = 0·408 at T2). IL-6 inversely correlated with lipoprotein(a) (r = −0·321 at T1) and LDL-cholesterol (r = −0·418 at T1). The IL-6 response could be predicted from a combination of the surgical severity and −174 G/C genotype. Conclusion: Although temporal associations did not indicate causality, these data provide a hypothesis to explain the inverse relationship between lipoprotein(a) and IL-6

    Stem cells and colorectal cancerogenesis: new insight

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    Intestinal stem cells are monoclonal, multipotent cells residing in the niches of intestinal cripts where they regulate colonic epithelial turnover. It has been recently demonstrated that alterations in signalling transduction of the intestinal stem cells is implicated in the onset of colorectal cancer. Chronic inflammation may be one of the mechanisms involved in cancerogenesis because failure of resident stem cells in repairing the epithelial damage for the chronic insult, recruits bone marrow stem cells, which can develop genetic mutations due to the inflamed environment, leading to cancer. The main mutations associated with colorectal cancer affect the most important cellular signalling pathway, the Wnt. Mutations of adenomatous polyposis coli (APC) tumor suppressor gene and β catenin oncogene are the most common and severe alterations of this pathway. Tissue invasion and metastatization require a two-side transition of cancer stem cells, from epithelial phenotypes to mesenchimal one (epithelial transition tumor, EMT) and from the mesenchimal phenotype to the epithelial one (mesenchymal transition tumor, MET) under the regulatory effects of the environment, the intracellular β catenin distribution and Pl6 cell cycle inhibitor. Stem cells provide normal intestinal epithelial turnover, but may also promote intestinal cancerogenesis, and, since the cancer stem cells during the mesenchimal status are resistant to the chemotherapy (which is active only on proliferating cells), they represent the true target of future therapeutic approaches in oncology

    MicroRNA in colorectal cancer: new perspectives for diagnosis, prognosis and treatment.

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    Colorectal cancer (CRC) is a common condition and represents a lethal disease, following a sequential progression from adenoma to carcinoma. Interfering with such natural history of CRC offers clues to prevention and cure, but current screening methods for CRC are still limited by unsatisfactory sensitivity and specificity. Novel diagnostic, prognostic tools are therefore being actively investigated for CRC. The discovery of microRNAs (miRNAs) has led to active research focusing on their role in cancer and several crucial pathways involving angiogenesis, cancer-stem-cell biology, epithelial-mesenchymal transition, formation of metastasis, and drug resistance. MiRNAs might soon represent novel prognostic and diagnostic tools in patients at high risk of CRC or being diagnosed with CRC. MiRNA might prove useful also as therapeutic tools, since dysregulation of miRNAs in cancer cells results in higher levels of messenger RNA (mRNA) specific to tumor promoter genes or tumor suppressor genes. Thus, novel anticancer therapies might originate from manipulation of oncogenic or tumor suppressor miRNAs in CRC. In this review, the innovative aspects of miRNA are discussed, with respect to biogenesis, their role in CRC, and their potential use as biomarkers. Before miRNAs can become available in the clinical setting, however, a number of large prospective studies are still required

    Effects of olive oil polyphenols on fatty acid synthase gene expression and activity in human colorectal cancer cells.

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    Oleuropein (OL) and hydroxytyrosol (HT), the main olive oil polyphenols, possess anti-proliferative effects in vitro. Fatty acid synthase, a key anabolic enzyme of biosynthesis of fatty acids, plays an important role in colon carcinoma development. Our aim was to investigate whether gene expression of FAS, as well as its enzymatic activity, is regulated by HT and OL in two human colon cancer cell lines, as HT-29 and SW620. In addition, we investigated the effects of these polyphenols on growth and apoptosis in these cells. FAS gene expression and activity in treated HT-29 and SW620 cells were evaluated by real-time PCR and radiochemical assay, respectively. Cell growth and apoptosis, after polyphenols treatment, were measured by MTT test and flow cytometry, respectively. The inhibition of proliferation, detected after HT treatment, was mediated by an inhibition of FAS expression and its enzymatic activity in SW620 cells, while the anti-proliferative effect in HT-29 cells seems to be independent from FAS. OL exerted an anti-proliferative effect only on SW620 cells with a mechanism which excluded FAS. Olive oil polyphenols used were able to induce apoptosis in both cell lines studied. The increase of apoptosis in these cells was accompanied by the block of cell cycle in the S phase. This study demonstrates that HT and OL may induce anti-proliferative and pro-apoptotic effects only in certain human colorectal cancer cell types. These effects are FAS mediated only in SW620 cells after treatment with HT

    Chemical signature of colorectal cancer: case–control study for profiling the breath print

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    Background: Effective screening for colorectal cancer can reduce mortality by early detection of tumours and colonic polyps. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a potential non-invasive diagnostic tool for detection of cancer. The aim of this study was to evaluate the reliability of breath-testing for colorectal cancer screening and early diagnosis using an advanced breath sampler. Methods: The exhaled breath of patients with colorectal cancer and non-cancer controls with negative findings on colonoscopy was collected using the ReCIVA® Breath Sampler. This portable device is able to capture the alveolar breath fraction without environmental contamination. VOCs were desorbed thermally and analysed by gas chromatography–mass spectrometry. The discriminatory ability of VOCs in detecting colorectal cancer was evaluated by receiver operating characteristic (ROC) curve analysis for each VOC, followed by cross-validation by the leave-one-out method, and by applying stepwise logistic regression analysis. Results: The study included 83 patients with colorectal cancer and 90 non-cancer controls. Fourteen VOCs were found to have significant discriminatory ability in detecting patients with colorectal cancer. The model with the diagnosis of cancer versus no cancer resulted in a statistically significant likelihood of discrimination of 173⋅45 (P <0⋅001), with an area under the ROC curve of 0⋅979. Cross-validation of the model resulted in a true predictive value for colorectal cancer of 93 per cent overall. Reliability of the breath analysis was maintained irrespective of cancer stage. Conclusion: This study demonstrated that analysis of exhaled VOCs can discriminate patients with colorectal cancer from those without. This finding may eventually lead to the creation of a smart online sensory device, capable of providing a binary answer (cancer/no cancer) and directing to further screening

    Chemical signature of colorectal cancer: case-control study for profiling the breath print

    No full text
    Background: Effective screening for colorectal cancer can reduce mortality by early detection of tumours and colonic polyps. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a potential non-invasive diagnostic tool for detection of cancer. The aim of this study was to evaluate the reliability of breath-testing for colorectal cancer screening and early diagnosis using an advanced breath sampler. Methods: The exhaled breath of patients with colorectal cancer and non-cancer controls with negative findings on colonoscopy was collected using the ReCIVA® Breath Sampler. This portable device is able to capture the alveolar breath fraction without environmental contamination. VOCs were desorbed thermally and analysed by gas chromatography-mass spectrometry. The discriminatory ability of VOCs in detecting colorectal cancer was evaluated by receiver operating characteristic (ROC) curve analysis for each VOC, followed by cross-validation by the leave-one-out method, and by applying stepwise logistic regression analysis. Results: The study included 83 patients with colorectal cancer and 90 non-cancer controls. Fourteen VOCs were found to have significant discriminatory ability in detecting patients with colorectal cancer. The model with the diagnosis of cancer versus no cancer resulted in a statistically significant likelihood of discrimination of 173·45 (P < 0·001), with an area under the ROC curve of 0·979. Cross-validation of the model resulted in a true predictive value for colorectal cancer of 93 per cent overall. Reliability of the breath analysis was maintained irrespective of cancer stage. Conclusion: This study demonstrated that analysis of exhaled VOCs can discriminate patients with colorectal cancer from those without. This finding may eventually lead to the creation of a smart online sensory device, capable of providing a binary answer (cancer/no cancer) and directing to further screening
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