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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Assessing dynamic micromechanical markers for the evaluation of the prostate for cancer

Good, Daniel William January 2016 (has links)
The diagnostic pathway for prostate cancer involves the blood test prostate specific antigen (PSA) which has high sensitivity but low specificity at age related reference ranges. The resultant clinical consequence is a large number of negative diagnostic studies (transrectal ultrasound guided biopsies - TRUS). There is a need for a secondary screening test to help improve on the current diagnostic pathway. Mechanical markers have been used previously to assess the prostate for disease with numerous ex-vivo reports of differences between benign and malignant prostates. There have been no in-vivo studies with direct elasticity assessment devices for prostate cancer detection. This thesis forms part of work in a collaborative study in conjunction with engineers who have created a microscale device, capable of dynamic elasticity assessment. The specific objectives of this thesis were to a) assess dynamic micromechanical markers for the detection and differentiation of clinically significant from insignificant prostate cancer b) to identify relationships between mechanical and histopathological variables in the ex-vivo and in-vivo environments and c) assess the potential for these markers to differentiate peri-prostatic tissues. A prospective study was set-up with full ethics and management approvals with patients undergoing a systematic mechanical assessment of their prostate using the E-finger device and after prostate excision a systematic ex-vivo mechanical assessment on a calibrated stage. The ex-vivo assessment allowed accurate histopathological and mechanical variable assessment in a controlled environment. 7-Tesla ex-vivo MRI scanning aided in assessing the limitations of mechanical assessment of the prostate. There were clear consistent differences between individual dynamic micromechanical markers for benign and tumour containing measurement areas in both environments. Modelling of these dynamic micromechanical markers yielded encouraging accuracy levels for the detection of prostate cancer and differentiation of significant from insignificant disease. There were associations between individual mechanical markers and important histopathological features associated with cancer (acinar size, tumour volume and reactive stroma). These markers showed promise and utility in the differentiation of prostate from bladder and rhabdosphincter. This work demonstrates the clear potential translational uses for dynamic micromechanical markers in the assessment of the prostate for cancer.
2

Identification of potential biomarkers for the detection of aggressive prostate cancer

Whiteland, Helen Louise January 2012 (has links)
No description available.
3

Investigation into taxane resistant breast cancer

Kenicer, Juliet Elisabeth Margaret January 2011 (has links)
One group of chemotherapeutics that are used successfully to treat breast cancer, alone or in combination with other agents, are the taxanes; paclitaxel and docetaxel. They act by interfering with the spindle microtubule dynamics of the cell causing cell cycle arrest. However, the complexities underlying the mechanism of action are yet to be fully elucidated. Arguably, one of the most significant problems with taxanes is chemoresistance. Unfortunately, some patients are intrinsically resistant to taxanes and others acquire resistance to taxanes as treatment advances. This problem is exacerbated by a lack of understanding of the mechanisms underlying taxane resistance. Isogenic breast cancer cell lines that were taxane resistant were generated to use as an experimental model. Paclitaxel resistant (PACR) MDA-MB-231, paclitaxel resistant ZR75-1 and docetaxel resistant (DOCR) ZR75-1 cell lines were successfully generated by incrementally increasing taxane dose in respective native cell lines in vitro. An extensive characterisation of each of the resistant cell lines was conducted, focussing primarily on the 25nM resistant cells which were determined to be the most clinically relevant dose of taxane. A suboptimal dose of 5nM, a “superoptimal” dose of 50nM and the native, taxane sensitive cells was included. Dose response cell count experiments were performed that confirmed taxane resistant cells had been generated. It was shown that MDA-MB-231 native cells were more sensitive to paclitaxel than the ZR75-1 native cells, suggesting that ZR75-1 cells may already have low level inherent resistance. The MDA-MB-231 25nM PACR cells were tested to determine whether they retained PACR when maintained in media containing no paclitaxel. MDA-MB-231 25nM PACR cells were maintained in a taxane free environment for six months and then rechallenged with taxane. When rechallenged, the PACR cells previously maintained in the absence of paclitaxel mirrored the pattern of growth of corresponding PACR cells that had been maintained in the presence of paclitaxel. This proved that in the absence of paclitaxel, PACR cells did not revert to parent phenotype. This meant that experiments could be designed to grow cell lines as xenografts in mice, (in the absence of paclitaxel) & bring in vitro experiments into an in vivo setting. Effects of taxane treatment on both native and resistant cells were analysed using flow cytometry. Paclitaxel treatment exerted G2/M block in native MDA-MB-231 cells but when PACR cells were treated with the same dose of paclitaxel no G2/M block was observed, suggesting that PACR cells had developed a mechanism for escaping G2/M block. ZR75-1 native lines were also investigated and we established that treatment with paclitaxel also exerted a G2/M block in these lines. In future studies this process will be repeated to investigate the effect of taxane treatment on the ZR75-1 PACR and DOCR lines. CD 1 nude mice were injected with cells from all five cell lines to grow xenografts, unfortunately MDA-MB-231 PACR cells failed to grow so they could not be used for further xenograft experiments. PACR, DOCR and Native ZR75-1 cells did successfully grow as xenografts in mice and confirmed that all 3 groups showed very similar growth patterns. A cross resistance experiment was conducted and it was determined that the DOCR xenografts maintained a taxane resistant phenotype to docetaxel, and not paclitaxel and the PACR xenografts may be perpetuate the paclitaxel resistant phenotype in xenografts and that there may be cross resistance to docetaxel in the paclitaxel resistant xenografts. This is the first time that taxane resistant cell lines grown in this way have been established as xenografts in mice. These cross resistance experiments represent novel findings and merit further investigation. Extensive genomic and transcriptomic analyses were carried out on the cell lines to help identify potential taxane resistance markers. aCGH experiments were carried out to compliment the illumina experiments. The first set of experiments used DNA from pooled whole female blood as ref sample and DNA from each of the native and taxane resistant cell lines as test samples. The second set of experiments used DNA from native cells as a ref sample and DNA from their respective taxane resistant cells as a test, which allowed areas of loss or gain to be tracked in the genome as resistance increased. In the MDA-MB-231 cell lines the following areas of loss extended with increasing resistance: 1p36.13-q44, 6p25.3-q12, 8p, 10p, 19q, X Chr and the following areas of gain 2p25.3-23.3, 3p24.3-q13.3, 4p16.1-q12, 5q14.3-q31.1, 8q21.13-24.3, 11q15.1-q25, centromeric 12, and centromeric 14. In the ZR75-1 PACR and DOCR cell lines the areas of loss extended with increasing resistance in the following regions: 7q, 12p and 16q. For gene expression analysis RNA was extracted from the MDA-MB-231 cell lines, labelled and hybridised them to illumina human ref 8 vs. 2 chips. Data showed a progressive increase in mRNA dysregulation as paclitaxel resistance increased. Eleven genes were dysregulated across all resistance levels in the PACR MDA-MB-231 cells when compared to the relative cell lines; RGS16, CLDN1, IL7R, P&PP1R14C, COBL, TRPV4, TSPAN8, CD33, NLRP2, P13, and PAGE5. The experiment was repeated using MDA-MB-231 PACR, ZR75-1 PACR and DOCR cells and resulting data was analysed to determine genes commonly dysregulated across resistance levels, between MDA-MB-231 PACR and ZR75-1 PACR and between ZR75-1 PACR and DOCR cell lines. An extensive literature search was conducted and established four genes of interest in the context of our genomic and transcriptomic experiments including AURKA, Mdr-1, Stathmin and YY1. The novel biomarkers identified in the illumina experiments were validated with complimentary qPCR gene expression experiments looking at expression levels of the eleven commonly dysregulated genes identified and a panel of 19 other genes with significantly increased or decreased expression as resistance increased including AURKA, Mdr-1, Stathmin and YY1. Western blots were performed with lysates from the cell lines using a standard panel of predictive breast cancer markers and AURKA, Mdr-1, Stathmin and YY1. Combining the data from the genomic study, the gene expression profile, qPCR and Western blotting it was established that Mdr-1 had increased expression in the taxane resistant ZR75-1 lines and YY1 had increased expression in the MDA-MB-231 PACR line. Material from the LAPATAX trial was used to observe any transcriptomic changes occurring in tumours following treatment with docetaxel and to compare them to changes identified in our in vitro and xenograft models, this allowed the final step to be taken into a translational environment. LAPATAX (EORTC 10054) is a phase I-II study of Lapatanib and Docetaxel as neoadjuvant treatment for HER-2 +ve locally advanced/inflammatory or large operable breast cancer. Tumour material from eighteen core biopsies pre and post treatment was obtained, the mRNA was extracted, labelled and hybridised to the illumina array. This allowed the changes in gene expression pre and post docetaxel treatment to be tracked. The gene expression data from the LAPATAX trial was combined with gene expression data from our cell line panel and identified two novel putative markers of taxane resistance DUSP1 and FOS. Although sample size is small this has provided extremely valuable evidence directly from the clinic. These two novel putative biomarkers are extremely intriguing and certainly merit further investigation, ideally using additional taxane treated breast tumour tissue. Ultimately, an isogenic in vitro model of taxane resistance was developed in two different cell lines and with two different taxanes within one cell line. The cell lines were characterised and the effect of the taxanes on the cell cycle was determined in the native and taxane resistant lines. Selected cell lines were grown as xenografts in mice and performed successful cross resistance studies upon them. A large transcriptomic and genomic analysis was conducted and has identified a panel of potential taxane resistance markers and areas of loss and gain in the genome perpetuated by increasing taxane resistance. This analysis was validated using qPCR and Western blotting. This allowed a panel of novel taxane resistance markers to be identified. In future studies it is hoped that these targets will be knocked down with shRNA to observe if the taxane resistant cell lines revert to the parental phenotype. In vitro studies will be conducted to find agents that may be used to reduce expression of these markers and restore sensitivity to taxanes and consequently restore the efficacy of these drugs in a clinical setting. As far as the author is aware this is the first time that isogenic taxane resistant cell lines have been generated and investigated in this way.
4

An evaluation of cancer biomarkers in normal ovarian epithelial cells and ovarian cancer cell lines

Fruka, Tayra January 2019 (has links)
Philosophiae Doctor - PhD / Introduction: Globally, there are over 190,000 new reported cases of ovarian cancers per annum. This comprises 3% to 4% of all cancers in women. Ovarian cancer is one of the leading causes of deaths in women. Ovarian cancer is the second most diagnosed gynaecological malignancy and over all the fifth cause leading to death among all types of cancer in the UK in 2004. More than 70% of epithelial ovarian cancers are diagnosed at an advanced stage. Consequently, the prognosis is poor and the mortality rate high. Thus, the survival rate is affected by how far the disease has progressed or spread. A dire need exists to identify ovarian cancer biomarkers, which could be used as good indicators of expression in ovarian cancer cells in vitro Aim: The aim of this study was to analyse selected cancer biomarkers, which are currently under intense investigation for their suitability to diagnose epithelial ovarian cancer at an early stage. These biomarkers were analysed in terms of their in vitro expression in normal epithelial cells and ovarian cancer cell lines, which allows for their genomic and proteomic classification. The expression analysis of each biomarker is related to the malignancy of a tumour and, therefore, advocates its use for potential future improvement of sensitive tumour markers. Methods: The primary human ovarian surface epithelial cell line (HOSEpiC), SKOV-3 cells and the OAW42 human epithelial ovarian tumour cell lines were used to evaluate the selected cancer biomarkers. Cells were cultured using appropriate media and supplements, and real-time quantitative polymerase chain reaction (RT-PCR) utilized to validate expression levels of the following genes: HDAC1, HDAC2, HDCA3, HDAC5, HDAC6, HDAC7, HDAC8, LPAR1, LPAR2, MUC16 and FOSL1, against normal housekeeping genes GAPDH and HPRT. In addition, immunocytochemistry was also used in the validation process of the aforementioned genes. Significance: ovarian cancer cells express gene signatures, which pose significant challenges for cancer drug development, therapeutics, prevention and management. The present study is an effort to explore ovarian cancer biomarkers to provide a better diagnostic method that may offer translational therapeutic possibilities to increase five- year survival rate. Results: HDAC5, HDAC6, LPAR1, LPAR2 and MUC16 expressed distinctively in ovarian cancers matched to other tissues or cancer types have already been identified by RT-QPCR and confirmed by immunocytochemistry and efforts to generate monoclonal antibodies to the other six genes (HDAC1, HDAC2, HDAC3, HDAC7, HDAC8 and FOSL1) encoded proteins are underway. Conclusions: here we provide strong evidence suggesting that HDAC5, HDAC6, LPAR1, LPAR2, except MUC16 are up regulated in ovarian cancer. These data were confirmed by examining Human Protein Atlas (HPA) databases, in addition to protein expression of HDAC5, HDAC6, LPAR1, LPAR2 and MUC16 in cells cytoplasm. For future prospective, using other techniques that assess the variant expression that could explain the release of these gene candidates into the circulation with serum tumour markers, and protein expression will be strengthened.
5

Klinický význam biomarkerů pro posouzení agresivity a prognozu nemalobuněčného karcinomu plic / The clinical relevance of biomarkers for aggression assessment and prognosis in non-small cell lung cancer

Pražáková, Markéta January 2011 (has links)
Aim: The aim of this thesis was to measure a large spectrum of biomarkers in serum or plasma of patients with operable stage of NSCLC and to evaluate and compare the clinical utility of these biomarkers in the three most important clinical applications for NSCLC: diagnosis, prognosis and postsurgery follow up care. Patients and methods: Total of 22 biomarkers with the most promising profiles were monitored: 8 standard tumor markers (cytokeratines Cyfra 21-1, TPA, TPS, and MonoTotal, CEA, SCC, TK, Chromogranin A) and 14 potential useful biomarkers including pro-inflammatory cytokines IL-6, IL-8, MCP-1, pro-angiogenic cytokine VEGF, matrix metaloproteinases MMP-1, MMP-2, MMP-7, MMP-9 and their inhibitors TIMP-1 and TIMP-2, adhesion molecules ICAM-1, VCAM-1, growth factor IGF-1, and PAI-1 stimulating tumor growth and angiogenesis. With a view of evaluating the clinical relevance of these markers for NSCLC we measured serum or plasma levels of these 22 markers in group of 93 patients with NSCLC undergoing radical surgery and in group of 20 patients with benign lung disease. For biomarker measurement were used conventional immunoanalytic routine methods (IRMA, REA, CLIA, MEIA, TRACE, ELISA) and multiplex immunoanalytic method. Results: Cyfra 21-1, MonoTotal, TPA, TPS, CEA, SCC, Chromogranin A, TIMP-1, MMP-1,...
6

Evaluation of nipple aspirate fluid as a diagnostic tool for early detection of breast cancer

Shaheed, Sadr-ul, Tait, C., Kyriacou, K., Linforth, R., Salhab, M., Sutton, Chris W. 11 January 2018 (has links)
Yes / There has been tremendous progress in detection of breast cancer in postmenopausal women, resulting in two-thirds of women surviving more than 20 years after treatment. However, breast cancer remains the leading cause of cancerrelated deaths in premenopausal women. Breast cancer is increasing in younger women due to changes in life-style as well as those at high risk as carriers of mutations in high-penetrance genes. Premenopausal women with breast cancer are more likely to be diagnosed with aggressive tumours and therefore have a lower survival rate. Mammography plays an important role in detecting breast cancer in postmenopausal women, but is considerably less sensitive in younger women. Imaging techniques, such as contrast-enhanced MRI improve sensitivity, but as with all imaging approaches, cannot differentiate between benign and malignant growths. Hence, current well-established detection methods are falling short of providing adequate safety, convenience, sensitivity and specificity for premenopausal women on a global level, necessitating the exploration of new methods. In order to detect and prevent the disease in high risk women as early as possible, methods that require more frequent monitoring need to be developed. The emergence of “omics” strategies over the last 20 years, enabling the characterisation and understanding of breast cancer at the molecular level, are providing the potential for long term, longitudinal monitoring of the disease. Tissue and serum biomarkers for breast cancer stratification, diagnosis and predictive outcome have emerged, but have not successfully translated into clinical screening for early detection of the disease. The use of breast-specific liquid biopsies, such as nipple aspirate fluid (NAF), a natural secretion produced by breast epithelial cells, can be collected non-invasively for biomarker profiling. As we move towards an age of active surveillance, home-based liquid biopsy collection kits are increasingly being applied and these could provide a paradigm shift where NAF biomarker profiling is used for routine breast health monitoring. The current status of established and newly emerging imaging techniques for early detection of breast cancer and the potential for alternative biomarker screening of liquid biopsies, particularly those applied to high-risk, premenopausal women, will be reviewed. / Proteomics research was supported by Yorkshire Cancer Research projects, BPP047 and B381PA, and co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research Promotion Foundation projects ΥΓΕΙΑ/ΒΙΟΣ/0311(ΒΙΕ/07) and NEKYP/0311/17.
7

Next generation transduction pathways for nano-bio-chip array platforms

Jokerst, Jesse Vincent 24 October 2014 (has links)
In the following work, nanoparticle quantum dot (QD) fluorophores have been exploited to measure biologically relevant analytes via a miniaturized sensor ensemble to provide key diagnostic and prognostic information in a rapid, yet sensitive manner—data essential for effective treatment of many diseases including HIV/AIDS and cancer. At the heart of this “nano-bio-chip” (NBC) sensor is a modular chemical/cellular processing unit consisting of either a polycarbonate membrane filter for cell-based assays, or an agarose bead array for detection of biomarkers in serum or saliva. Two applications of the NBC sensor system are described herein, both exhibiting excellent correlation to reference methods ((R² above 0.94), with analysis times under 30 minutes and sample volumes below 50 [mu]L. First, the NBC sensor was employed for the sequestration and enumeration of T lymphocytes, cells specifically targeted by HIV, from whole blood samples. Several different conjugation methods linking QDs to recognition biomolecules were extensively characterized by biological and optical methods, with a thiol-linked secondary antibody labeling scheme yielding intense, specific signal. Using this technique, the photostability of QDs was exploited, as was the ability to simultaneously visualize different color QDs via a single light pathway, effectively reducing optical requirements by half. Further, T-cell counts were observed well below the 200/[mu]L discriminator between HIV and AIDS and across the common testing region, demonstrating the first reported example of cell counting via QDs in an enclosed, disposable device. Next, multiplexed bead-based detection of cancer protein biomarkers CEA, Her-2/Neu, and CA125 in serum and saliva was examined using a sandwich immunoassay with detecting antibodies covalently bound to QDs. This nano-based signal was amplified 30 times versus molecular fluorophores and cross talk in multiplexed experiments was less than 5%. In addition, molecular-level tuning of recognition elements (size, concentration) and agarose porosity resulted in NBC limits of detection two orders of magnitude lower than ELISA, values competitive with the most sensitive methods yet reported (0.021 ng/mL CEA). Taken together, these efforts serve to establish the valuable role of QDs in miniaturized diagnostic devices with potential for delivering biomedical information rapidly, reliably, and robustly. / text
8

Fabrication of a label-free electrochemical immunosensor using a redox active ferrocenyl dendrimer

Chandra, Sudeshna, Gäbler, Christian, Schliebe, Christian, Lang, Heinrich, Bahadur, Dhirendra 06 March 2017 (has links) (PDF)
We report an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as a voltammetric transducer. The ferrocenyl dendrimer N(CH2CH2C(O)NHCH2CH2NHC(O)Fe(η5-C5H4)(η5-C5H5))(CH2CH2N(CH2CH2C(O)NHCH2CH2NHC(O)Fe(η5-C5H4)(η5-C5H5))2)2 (G2Fc) was used as a functional moiety to immobilize the antibody on the surface of the electrode. A sandwich immunosensor of the type IgG/Bovine serum albumin (BSA)/anti-IgG/G2Fc/glassy carbon electrode (GCE) was fabricated. The electrochemical properties of G2Fc were thoroughly studied in aqueous and non-aqueous electrolytes with varying scan rates. The incubation time was optimized for better analytical performance of the immunosensor. It is found that the developed amperometric immunosensor is sensitive to a concentration of IgG as low as 2 ng mL−1. / Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
9

Efeitos do exercício físico associado à luz contínua na carcinogênese colônica em ratos / Influence pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise

Frajacomo, Fernando Tadeu Trevisan 29 April 2010 (has links)
O exercício físico tem sido proposto como uma terapia não farmacológica eficaz para a prevenção e tratamento de neoplasias, com destaque ao câncer de cólon. O presente estudo visa investigar o papel da glândula pineal sobre carcinogênese colônica experimental de ratos submetidos ao exercício físico Dessa forma, propusemos investigar os biomarcadores colônicos de câncer, foco de cripta aberrante (FCA), antígeno nuclear de proliferação nuclear (PCNA), expressão de ciclooxigenase-2 (COX-2) e Caspase 3. Além de parâmetros oxidativos hepáticos de peroxidaçao lipídica e gluationa reduzida (GSH). O Estudo foi conduzido através dos grupos experimentais controle (C), luz contínua (L), Exercício (E) e luz contínua associada ao Exercício (LE) e os mesmos grupos expostos ao carcinógeno químico 1,2-Dimetilhidrazina (DMH). Exercício físico foi realizado pelo modelo de natação, 5 dias por semana durante 10 semanas. Após o periodo de treinamento, os animais foram sacrificados, sendo coletadas amostras de sangue e fígado e colón para análises. O estudo do fígado revelou uma significativa influência do DMH na modulação dos parâmetros oxidativos. Já as análises colônicas dos FCAs e do PCNA mostraram-se controlados pelo exercício físico realizado em condições de normais do ritmo circadiano ao passo que em condições de desbalanço fisiológico da glândula pineal pela exposição luz constante, esses mesmos efeitos foram revertidos em comparação ao demais grupos (LED>LD>D>ED=p<0.001), aumento este acompanhado pela redução dos níveis plasmáticos de melatonina neste grupo. Em conclusão, nossos dados alertam para a forte influência da glândula pineal sobre o complexo de adapatações do exercício físico no tecido colônico de ratos expostos a um carcinógeno químico. / Physical activity has been proposed as a nonpharmacologic therapy for the prevention and treatment of cancer patients, with emphasis on colon cancer. The current study aims to investigate the role of the pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise. We proposed to analyze cancer colonics biomarkers, Aberrant Foci Crypt (ACFs), proliferating cell nuclear antigen (PCNA) and Caspase-3, inflammation parameters cyclooxigenase-2 (COX-2) and liver oxidative enzymes reduced glutathione (GSH) and lipid peroxidation (MDA). Experimental design was constructed by control group (C), continuous light (L), exercise (E) and continuous light plus exercise (LE) and the same groups with chemical carcinogen 1,2 dimethyl-hydrazine (DMH). Exercise training groups were performed swimming exercise 5 d-wk1 for 10 wk. After training period rats were sacrificed. Blood samples and liver were collected to analyses and colon was processed for histological and immunohistochemistry examination. The study of the liver revealed a significant effect of DMH in the modulation of oxidative parameters. Since the analysis of colonic FCAs and PCNA were shown to be controlled by exercise carried out with a normal circadian rhythm while in conditions of physiological imbalance of the pineal gland by constant light exposure, these effects were reversed in comparison to other groups (LED> LD> D> ED = p <0.001), increase accompanied by reduced plasma levels of melatonin in this group. In conclusion, our data call attention to the strong influence of the pineal gland on the complex adaptations of physical exercise on colonic mucosa of rats exposed to a chemical carcinogen.
10

Efeitos do exercício físico associado à luz contínua na carcinogênese colônica em ratos / Influence pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise

Fernando Tadeu Trevisan Frajacomo 29 April 2010 (has links)
O exercício físico tem sido proposto como uma terapia não farmacológica eficaz para a prevenção e tratamento de neoplasias, com destaque ao câncer de cólon. O presente estudo visa investigar o papel da glândula pineal sobre carcinogênese colônica experimental de ratos submetidos ao exercício físico Dessa forma, propusemos investigar os biomarcadores colônicos de câncer, foco de cripta aberrante (FCA), antígeno nuclear de proliferação nuclear (PCNA), expressão de ciclooxigenase-2 (COX-2) e Caspase 3. Além de parâmetros oxidativos hepáticos de peroxidaçao lipídica e gluationa reduzida (GSH). O Estudo foi conduzido através dos grupos experimentais controle (C), luz contínua (L), Exercício (E) e luz contínua associada ao Exercício (LE) e os mesmos grupos expostos ao carcinógeno químico 1,2-Dimetilhidrazina (DMH). Exercício físico foi realizado pelo modelo de natação, 5 dias por semana durante 10 semanas. Após o periodo de treinamento, os animais foram sacrificados, sendo coletadas amostras de sangue e fígado e colón para análises. O estudo do fígado revelou uma significativa influência do DMH na modulação dos parâmetros oxidativos. Já as análises colônicas dos FCAs e do PCNA mostraram-se controlados pelo exercício físico realizado em condições de normais do ritmo circadiano ao passo que em condições de desbalanço fisiológico da glândula pineal pela exposição luz constante, esses mesmos efeitos foram revertidos em comparação ao demais grupos (LED>LD>D>ED=p<0.001), aumento este acompanhado pela redução dos níveis plasmáticos de melatonina neste grupo. Em conclusão, nossos dados alertam para a forte influência da glândula pineal sobre o complexo de adapatações do exercício físico no tecido colônico de ratos expostos a um carcinógeno químico. / Physical activity has been proposed as a nonpharmacologic therapy for the prevention and treatment of cancer patients, with emphasis on colon cancer. The current study aims to investigate the role of the pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise. We proposed to analyze cancer colonics biomarkers, Aberrant Foci Crypt (ACFs), proliferating cell nuclear antigen (PCNA) and Caspase-3, inflammation parameters cyclooxigenase-2 (COX-2) and liver oxidative enzymes reduced glutathione (GSH) and lipid peroxidation (MDA). Experimental design was constructed by control group (C), continuous light (L), exercise (E) and continuous light plus exercise (LE) and the same groups with chemical carcinogen 1,2 dimethyl-hydrazine (DMH). Exercise training groups were performed swimming exercise 5 d-wk1 for 10 wk. After training period rats were sacrificed. Blood samples and liver were collected to analyses and colon was processed for histological and immunohistochemistry examination. The study of the liver revealed a significant effect of DMH in the modulation of oxidative parameters. Since the analysis of colonic FCAs and PCNA were shown to be controlled by exercise carried out with a normal circadian rhythm while in conditions of physiological imbalance of the pineal gland by constant light exposure, these effects were reversed in comparison to other groups (LED> LD> D> ED = p <0.001), increase accompanied by reduced plasma levels of melatonin in this group. In conclusion, our data call attention to the strong influence of the pineal gland on the complex adaptations of physical exercise on colonic mucosa of rats exposed to a chemical carcinogen.

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