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1
Kho, Sunn Sunn Patricia. "Optimising Adjuvant Treatment for Colorectal Cancer." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/9470.
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The aim of the thesis is to optimize adjuvant treatment for colorectal cancer (CRC) patients. CRC treatment has improved over the decades resulting in improved overall survival of patients. The 5-year overall survival for CRC in the US between 1975 – 1979 was 50.6% while by 2004; it had improved to 65.9%. This is largely due to improvements in surgical and radiation techniques, screening initiatives and more effective chemotherapy drugs. However, when compared to the 5-year overall survival for breast cancer in 2004 of 89.9% (SEER data), it is clear that further improvements in CRC treatment are needed. This thesis evaluated different approaches to further improve overall survival rates and to reduce the acute and late toxicities associated with adjuvant treatment. One of the approaches was to attempt to personalize treatment for colorectal cancer patients using prognostic and predictive biomarkers. The group of patients selected for review were Stage C colon and rectal patients as the risk of recurrence is very high and the 5 year overall survival remains poor at 28% for colon cancer and 33% for rectal cancer. In this era of personalized medicine, the hope is to be able to tailor treatment regimens according to the patient and disease stage to reduce toxicity and improve efficacy. A retrospective analysis of the survival of Stage C rectal cancer patients in a public teaching hospital who received adjuvant chemotherapy after a curative resection was conducted to evaluate the role of adjuvant chemotherapy alone without radiotherapy. An original research study evaluating the role of a candidate marker, s100A4 in the treatment of Stage C colon cancer was also performed to evaluate the possible role of a new candidate biomarker s100A4 in the prognostication of Stage C colon cancer.
2
Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133839.
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Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Karger, 2002. https://tud.qucosa.de/id/qucosa%3A27540.
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Smeenk, Henri Gerard. "Surgical and adjuvant treatment of pancreatic cancer." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13713.
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Bossaer, John B., and Christian M. Thomas. "Adjuvant Treatment of Newly Diagnosed Breast Cancer." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/2313.
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Buijs, Ciska. "Long-term side effects of adjuvant breast cancer treatment." [S.l. : Groningen : s.n. ; University Library of Groningen] [Host], 2008. http://irs.ub.rug.nl/ppn/306087480.
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Mastrandrea, Nicholas Joseph. "Pentoxifylline As An Adjuvant Treatment In Renal Cell Carcinoma." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/337293.
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Cyclin D1, a proto-oncogene, is required for progression from the G1 phase into the S phase of the cell cycle. Over-expression of cyclin D1 causes an increase in cell cycle progression and cell proliferation, implicating it in a variety of cancers including renal cell carcinoma (RCC). The rodent RCC cell model, QTRRE, and human RCC cell models, ACHN, 786-O and Caki-2, exhibit elevated levels of cyclin D1. Pentoxifylline (PTX), a non-specific phosphodiesterase inhibitor, is an FDA-approved hemorheologic agent used to treat intermittent claudication, stemming from peripheral vascular diseases, as well as other diseases involving defective locoregional blood flow. Treatment of QTRRE, ACHN, 786-O and Caki-2 with PTX caused a time- (0-24 hrs) and dose- (0-1.0 mg/mL) dependent decrease of cyclin D1 protein and p-Rb levels in whole cell lysate as well as cytosolic and nuclear fractions, albeit, to different extents within the models. Concomitant with cyclin D1 and p-Rb decrease, enhanced G1 phase cell cycle arrest was observed in the RCC models. Mechanistic studies in these RCC cell models were carried out to determine PTXs mechanism of action with regard to cyclin D1 protein level decrease. RT-PCR analysis showed no significant changes in cyclin D1 mRNA copy number in time- (0-24 hrs) and dose- (0-1.0 mg/mL) dependent PTX treatments. However, such treatments caused decrease in p-4EBP1 (Ser65), p-4EBP1 (Thr70), and p-4EBP1 (Thr37/46). Because PTX's ability to decrease cyclin D1 protein was prevented in the presence of the proteasome inhibitor, MG-132, studies were performed to determine whether cyclin D1 stability was decreased during PTX treatment. Cyclin D1 degradation is initiated by phosphorylation of residue Thr286 by GSK-3β. Inhibition of GSK-3β with LiCl or knockdown via siRNA in the presence of PTX failed to block cyclin D1 decrease. Moreover, PTX treatment in the presence of MG-132 revealed no significant increase in cyclin D1 p-Thr286 compared to control. Finally, using the protein synthesis inhibitor, CHX, PTX caused no significant decrease in cyclin D1 t₁/₂ (wt-HA and T286A-HA) compared to control. Sorafenib, a broad-spectrum (cRAF, bRAF, KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-β) kinase inhibitor, is FDA-approved for the treatment of RCC. Studies with sorafenib and PTX in the ACHN cell model were carried out to determine PTXs possible adjuvant role in inhibiting cell growth via cyclin D1 decrease and G1 phase arrest. MTS data showed PTX potentiates the anti-proliferative effects of sorafenib. PTX pre-treatment for 24 hrs was also lowered the effective dose of sorafenib from 50 μM to 5 μM. Further, ACHN xenograft tumor volumes from mice treated with PTX and sorafenib displayed significantly higher tumor growth inhibition compared to either drug treatment alone or vehicle. Finally, drug treated ACHN xenograft tissue displayed significantly lower cyclin D1, p-RB and p-4EBP1 levels. These results demonstrate a novel anti-cancer property of PTX and suggest its use as a possible adjuvant therapy in RCC treatment should be further explored.
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Giallourou, Natasa. "Watercress as a nutritional adjuvant treatment in breast cancer." Thesis, University of Reading, 2017. http://centaur.reading.ac.uk/76171/.
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Breast cancer is a leading cause of cancer related mortality globally, and epidemiological studies suggest a link between healthy nutrition and cancer prevention. Members of the Brassicaceae family, including watercress, have been extensively studied for their anti-cancer and anti-genotoxic potential. Watercress has a complex phytonutrient profile characterised by high levels of carotenoids, flavonols and glucosinolates. Extracts of watercress exhibit strong antioxidant capacity in vitro. Watercress and its components have been associated with the inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis in in vitro cancer cell models. Phenethyl isothiocyanate (PEITC) is a glucosinolate break-down product and watercress is the richest dietary source of it. It has received considerable attention for its anti-cancer properties and has been tested in a number of clinical trials. In this thesis, the effects of crude watercress extract and PEITC on the metabolic and phenotypic responses in breast cancer and healthy breast tissue cell lines were examined. Radiotherapy is the most common treatment modality for breast cancer patients; it functions by killing cancer cells but it simultaneously damages healthy tissues. We set out to examine synergistic responses to irradiation and watercress or PEITC exposures in breast cancer cells and we further investigated whether watercress or PEITC can be protective against radiation induced collateral damage. Watercress and PEITC effectively modulated important cancer cell metabolic pathways associated with anti-cancer endpoints such as cell cycle arrest and DNA damage. In this thesis, PEITC has been shown to enhance the sensitivity of cancer cells to irradiation making the cancer killing process more effective, whereas watercress can protect healthy breast cells from radiation induced damage. These observations appear to be mediated by the ability of PEITC and other phytochemicals in watercress to interact with the antioxidant glutathione. The results obtained from this work remain to be validated in a clinical setting.
9
Wirth, Manfred P., and Oliver W. Hakenberg. "Curative Treatment of Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133890.
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The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes availableDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
10
Andersson, Anna. "Adjuvant and Down-Staging Treatment with Imatinib in Gastrointestinal Stromal Tumours." Thesis, Linköping University, Engelska: Faculty of Health Sciences, Medical Programme, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11060.
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Background: GISTs are gastrointestinal mesenchymal tumours that express the type III receptor tyrosine kinase KIT. The KIT proto-oncogene encodes the receptor KIT. Most GISTs have gain-of-function mutations in the KIT or PDGFRA gene. The tyrosine kinase is therefore continuously activated leading to ligand-independent dimerization. Imatinib mesylate (Glivec®) is considered to be the first-line palliative treatment. The activated form of the KIT receptor tyrosine kinase is inhibited by imatinib. The aim of the study was to compare the survival of patients treated with either adjuvant or down-staging imatinib with historic controls treated with radical surgery (R0) only.
Methods: A historic control group was chosen from a population-based series from western Sweden (population 1.6 million) that matched the adjuvant (n=23) and down-staging (n=7) groups respectively. Mutation analysis was performed in all cases with bidirectional direct sequencing. The recurrence-free survival was calculated.
Results: There was only one recurrence (4 %) in the adjuvant group, and no recurrences in the down-staging study group, compared to 32/48 patients (67 %) in the control group. Tumour size decreased in diameter from 20 cm to 11 cm with down-staging treatment.
Conclusion: Adjuvant imatinib improves recurrence-free survival in R0 resected patients. Down-staging treatment with imatinib is recommended for patients with large tumours or metastases. The importance of mutation analysis was established.
11
Kirby, Anna M. "Optimising Target Volume Definition and Treatment Position for Adjuvant Breast Radiotherapy." Thesis, Institute of Cancer Research (University Of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516272.
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Alencar, Victor Hugo Medeiros. "AvaliaÃÃo do Tratamento Adjuvante com Tamoxifeno em Mulheres com CÃncer de Mama." Universidade Federal do CearÃ, 2006. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6067.
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nÃo hÃO cÃncer de mama foi descrito hà muitos anos e documentado, pela primeira vez, por Imhotep, mÃdico, astrÃlogo e arquiteto egÃpcio, nascido em 2.650 antes de Cristo (a.C.) que recomendava Ãquela Ãpoca, como tratamento, a cauterizaÃÃo do tecido doente. Tamoxifeno à o fÃrmaco mais prescrito no tratamento do cÃncer de mama. Sua utilizaÃÃo à principalmente na modalidade adjuvante, em pacientes prà ou pÃs menopausadas, receptor de estrÃgeno e/ou progesterona positivos. à tambÃm utilizado no tratamento da doenÃa localmente avanÃada e metastÃtica e em menor proporÃÃo nas pacientes com contra-indicaÃÃo formal de cirurgia ou que se recusam a se submeter a esta modalidade de tratamento. Na neo-adjuvÃncia à utilizada apenas em ensaios clÃnicos. O tamoxifeno tambÃm diminui, na adjuvÃncia por cinco anos, a probabilidade de recidiva em 47% e de morte por cÃncer de mama em 26% e os dois principais efeitos colaterais, apesar de raros, sÃo aumento da prevalÃncia de cÃncer de endomÃtrio e de fenÃmenos tromboembÃlicos. Este estudo teve como objetivo principal avaliar as pacientes portadoras de cÃncer de mama, no Instituto do CÃncer do CearÃ, tratadas com tamoxifeno de forma adjuvante, no perÃodo de janeiro de 1993 a 1996, com relaÃÃo aos principais benefÃcios e efeitos colaterais, bem como anÃlise de sobrevivÃncia. ProntuÃrios de setecentos e quarenta e duas pacientes foram analisados no que diz respeito aos dados sÃcio- demogrÃficos, idade, status menopausal, estadiamento clÃnico e patolÃgico, dosagem de receptores de estrÃgeno e progesterona, casos de cÃncer de endomÃtrio, principais sÃtios de metÃstases, modalidade de tratamento cirÃrgico, radioterÃpico e quimioterÃpico, causas de Ãbito, tipo histolÃgico, status dos linfonodos axilares e anÃlise de sobrevivÃncia de acordo com o estadiamento. Concluiu-se que a maioria dos dados estÃo de acordo com a literatura e que o prejuÃzo da anÃlise foi resultante da qualidade dos registros realizados nos prontuÃrios, devendo cada vez mais os mÃdicos serem estimulados a documentar, de forma clara e legÃvel, o maior nÃmero de informaÃÃes possÃveis, nÃo apenas as positivas, mas todas aquelas que, mais freqÃentemente, possam ter relaÃÃo com a utilizaÃÃo de qualquer medicamento prescrito.
O cÃncer de mama foi descrito hà muitos anos e documentado, pela primeira vez, por Imhotep, mÃdico, astrÃlogo e arquiteto egÃpcio, nascido em 2.650 antes de Cristo (a.C.) que recomendava Ãquela Ãpoca, como tratamento, a cauterizaÃÃo do tecido doente. Tamoxifeno à o fÃrmaco mais prescrito no tratamento do cÃncer de mama. Sua utilizaÃÃo à principalmente na modalidade adjuvante, em pacientes prà ou pÃs menopausadas, receptor de estrÃgeno e/ou progesterona positivos. à tambÃm utilizado no tratamento da doenÃa localmente avanÃada e metastÃtica e em menor proporÃÃo nas pacientes com contra-indicaÃÃo formal de cirurgia ou que se recusam a se submeter a esta modalidade de tratamento. Na neo-adjuvÃncia à utilizada apenas em ensaios clÃnicos. O tamoxifeno tambÃm diminui, na adjuvÃncia por cinco anos, a probabilidade de recidiva em 47% e de morte por cÃncer de mama em 26% e os dois principais efeitos colaterais, apesar de raros, sÃo aumento da prevalÃncia de cÃncer de endomÃtrio e de fenÃmenos tromboembÃlicos. Este estudo teve como objetivo principal avaliar as pacientes portadoras de cÃncer de mama, no Instituto do CÃncer do CearÃ, tratadas com tamoxifeno de forma adjuvante, no perÃodo de janeiro de 1993 a 1996, com relaÃÃo aos principais benefÃcios e efeitos colaterais, bem como anÃlise de sobrevivÃncia. ProntuÃrios de setecentos e quarenta e duas pacientes foram analisados no que diz respeito aos dados sÃcio- demogrÃficos, idade, status menopausal, estadiamento clÃnico e patolÃgico, dosagem de receptores de estrÃgeno e progesterona, casos de cÃncer de endomÃtrio, principais sÃtios de metÃstases, modalidade de tratamento cirÃrgico, radioterÃpico e quimioterÃpico, causas de Ãbito, tipo histolÃgico, status dos linfonodos axilares e anÃlise de sobrevivÃncia de acordo com o estadiamento. Concluiu-se que a maioria dos dados estÃo de acordo com a literatura e que o prejuÃzo da anÃlise foi resultante da qualidade dos registros realizados nos prontuÃrios, devendo cada vez mais os mÃdicos serem estimulados a documentar, de forma clara e legÃvel, o maior nÃmero de informaÃÃes possÃveis, nÃo apenas as positivas, mas todas aquelas que, mais freqÃentemente, possam ter relaÃÃo com a utilizaÃÃo de qualquer medicamento prescrito.
Breast cancer is a disease that was described many years ago and has been documented, for the first time, by Imhotep, physician, astrologer and Egyptian architect, born in 2.650 before Christ (b.C.), who recommended, at that time, as a way of treatment, cauterization of the diseased tissue. Tamoxifen is the drug more prescribed in the treatment of breast cancer. Itâs use is mainly in the adjuvant modality, in pre or post menopaused patients positive estrogen and/or progesteron receptors. Itâs used in the treatment of locally advanced and metastatic disease and in smaller proportion in patients with formal contraindication of surgery or that refuse to submit this treatment modality. In the neoadjuvancy it is just used in clinical research. The tamoxifen also reduces in the adjuvant modality during five years, the probability of recurrence in 47% and deaths caused by breast cancer in 26% and the two main side effects, in spite of rare, are the increase of the prevalence of endometrial cancer and of thromboembolic phenomenas. This study had as main objective to evaluate the patients, breast cancer bearers, in the Institute of Cancer of CearÃ, treated with tamoxifen in the adjuvant form in the period of 1993 to 1996 regarding the main benefits and side effects, as well as survival analysis. Seven hundred forty-two patientsâprontuaries were analyzed in respect to the demographic datas, age, menopausal status, clinical and pathological staging, dosage of estrogen and/or progesterone receptors, cases of endometrial cancer, main local metastasis, modality of surgical treatment, radiotherapy and chemotherapy, death causes, histological type, status of the axillary lymph nodes and survival analysis in agreement with the staging. We concluded that most of the data is in agreement with the literature and that the demage of the analysis was resulting from the quality accomplished found in the prontuaries. Also, doctors should be more and more stimulated to document, in a clear and readable way, the largest number of possible information, not just the positive ones, but all those that more frequently can have relationships with the use of any prescribed medicine.
Breast cancer is a disease that was described many years ago and has been documented, for the first time, by Imhotep, physician, astrologer and Egyptian architect, born in 2.650 before Christ (b.C.), who recommended, at that time, as a way of treatment, cauterization of the diseased tissue. Tamoxifen is the drug more prescribed in the treatment of breast cancer. Itâs use is mainly in the adjuvant modality, in pre or post menopaused patients positive estrogen and/or progesteron receptors. Itâs used in the treatment of locally advanced and metastatic disease and in smaller proportion in patients with formal contraindication of surgery or that refuse to submit this treatment modality. In the neoadjuvancy it is just used in clinical research. The tamoxifen also reduces in the adjuvant modality during five years, the probability of recurrence in 47% and deaths caused by breast cancer in 26% and the two main side effects, in spite of rare, are the increase of the prevalence of endometrial cancer and of thromboembolic phenomenas. This study had as main objective to evaluate the patients, breast cancer bearers, in the Institute of Cancer of CearÃ, treated with tamoxifen in the adjuvant form in the period of 1993 to 1996 regarding the main benefits and side effects, as well as survival analysis. Seven hundred forty-two patientsâprontuaries were analyzed in respect to the demographic datas, age, menopausal status, clinical and pathological staging, dosage of estrogen and/or progesterone receptors, cases of endometrial cancer, main local metastasis, modality of surgical treatment, radiotherapy and chemotherapy, death causes, histological type, status of the axillary lymph nodes and survival analysis in agreement with the staging. We concluded that most of the data is in agreement with the literature and that the demage of the analysis was resulting from the quality accomplished found in the prontuaries. Also, doctors should be more and more stimulated to document, in a clear and readable way, the largest number of possible information, not just the positive ones, but all those that more frequently can have relationships with the use of any prescribed medicine.
13
Coldman, Andrew James. "The development of resistance to anticancer agents." Thesis, University of British Columbia, 1986. http://hdl.handle.net/2429/26975.
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The mechanism of resistance of tumor cells to chemotherapeutic agents is explored using probabilistic methods where it is assumed that resistant cells arise spontaneously with a defined frequency. The resistance process is embedded in a discrete time Markov branching process which models the growth of the tumor and contains three seperate cell types: stem, transitional and end cells. Using the asymptotic properties of such models it is shown that the proportion of each type of cell converge to constants almost surely. It is shown that the parameters relating to stem cell behaviour determine the asymptotic behaviour of the system. It is argued that for biologically likely parameter values, cure of the tumor will occur if, and only if, all stem cells are eliminated.
A model is developed for the acquisition of resistance by stem cells to a single drug. Probability generating functions are derived which describe the behaviour of the process after an arbitrary sequence of drug treatments. The probability of cure, defined as the probability of ultimate extinction of the stem cell compartment, is characterised as the central quantity reflecting the success of therapeutic intervention. Expressions for this function are derived for a number of experimental situations. The effects of variation in the parameter values are examined.
The model is extended to the case where two anticancer drugs are available and formulae for the probability of cure are developed. The problem of therapeutic scheduling is examined and under situations where drugs are of "equal" effectiveness, but may not be given together, it is shown that the mean number of tumor cells is minimised by sequential alternation of the drugs.
The models are applied to data collected on the L1210 leukemia treated by the drugs Cyclophosphamide and Arabinosylcytosine. In both cases the analysis of the data provide evidence that resistant cells arise spontaneously with a frequency of approximately 10⁻⁷ per division. When applied to human breast cancer, the model indicates that neoadjuvant
therapy is unlikely to greatly influence the likelihood that the patient will die from the growth of drug-resistant cells.Science, Faculty of
Statistics, Department of
Graduate
14
Bennett, Barbara Kaye School of Medicine UNSW. "Characterising the nature of postcancer fatigue in women treated for early-stage breast cancer." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/31202.
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The problem investigated Four studies investigated the phenomenon of cancer-related fatigue (CRF) in women who had received adjuvant treatment for early-stage breast cancer, with a view to reducing the diagnostic uncertainty surrounding the syndrome and thus facilitating progress in both clinical management and aetiological research. Procedures and results A cross-sectional study of 109 women compared a ???cancer-specific??? self-report questionnaire (FACT-F) (canvassing fatigue symptoms) and a more generic questionnaire (SPHERE) (identifying depression and fatigue). Thirty-seven percent of women reported fatigue. Overall in 20%, fatigue was associated with psychological distress. Seventeen percent of women had fatigue but no depression. A qualitative study utilised focus groups to identify and compare the distinctive features of CRF with those of women with chronic fatigue syndrome (CFS). A similar set of symptoms was found in both groups, including overwhelming fatigue, un-refreshing sleep and subjective concentration problems. However, women with CFS also reported myalgia and arthralgia. Using the Structured Clinical Interview for Neurasthenia- SCIN, the third study compared the symptoms of three groups of women with fatigue: those with CRF, CFS or major depression. The detailed ???interviewer guide??? provided explicit directions for evaluating and classifying symptoms. This study confirmed the core symptom of ???profound fatigue unrelieved by rest???, and additional features that distinguished between the clinical diagnoses. The fourth study compared features of the evolution of clinically-identified fatigue syndromes in women from two prospective cohort studies; women with post-cancer fatigue (PCF) and women with post-infective fatigue syndrome (PIFS). Major conclusions A syndrome of PCF, present at least six months following adjuvant treatment and unexplained by medical or psychiatric disorder was investigated. The characteristics of PCF and those of CFS are very similar, with the fatigue state having indistinguishable descriptors. Longitudinal evaluation of the symptom complexes of PCF and PIFS suggests divergent pathways may be relevant. Co-morbid features like sleep disturbance; physical deconditioning and mood disturbance may be implicated as factors in the evolution and prolongation of PCF. These studies provide a basis for a more uniform and rigorous classification system - a necessary first step towards advancing the field both in investigating aetiology and new intervention strategies.
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Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133551.
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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantageDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Rosell, Johan. "Long-term effects of adjuvant tamoxifen treatment on cardiovascular disease and cancer." Doctoral thesis, Linköpings universitet, Avdelningen för kliniska vetenskaper, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-112085.
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The aims of this thesis were to investigate the long-term effects of adjuvant tamoxifen treatment on breast cancer recurrence and mortality, cardiovascular disease, and the incidence of secondary cancer. Between 1982 and 1992, postmenopausal patients with early stage breast cancer were included in a randomized clinical study of 2 or 5 years of postoperative tamoxifen therapy. The trial was planned by the Swedish Breast Cancer Group, and it included 4610 patients. Follow-up on causes of death, hospitalizations and secondary cancers were obtained from national population-based registries. All-cause mortality, breast cancer-specific mortality and mortality from coronary heart disease were decreased in the 5-year group, but the incidence of endometrial cancer was increased (Paper I). The incidence and mortality of cerebrovascular diseases were increased during the active treatment phase, and reduced after the active treatment (Paper II). Similar results were seen for subgroups of cerebrovascular diseases such as stroke and ischemic stroke. In the 5-year group, the morbidity from coronary heart disease was reduced during treatment but not after treatment was stopped (Paper III). This was the case also for heart failure and for atrial fibrillation/flutter. For secondary cancers the lung cancer risk was reduced, as well as the lung cancer mortality (Paper IV). An increased risk was observed for endometrial cancer, but appeared to decrease over time. The risk of contralateral breast cancer was reduced, with most of the reduction after treatment was stopped. For distance recurrences the risk was reduced both during treatment and a few years after treatment was stopped. The breast cancer mortality was also reduced, especially during the post-treatment phase.
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Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Karger, 2003. https://tud.qucosa.de/id/qucosa%3A27515.
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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Wirth, Manfred P., and Oliver W. Hakenberg. "Curative Treatment of Prostate Cancer." Karger, 1999. https://tud.qucosa.de/id/qucosa%3A27546.
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The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes available.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Livingstone, Ann. "Patient and Clinician Preferences for Adjuvant Immunotherapy as Treatment of Stage III Melanoma." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29605.
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Patient preferences are used to inform healthcare funding decisions, contribute to value assessment, and determine end-user acceptability of treatment. Understanding the preferences for adjuvant immunotherapy of patients with stage III resected melanoma and their clinicians is essential to inform clinical decision-making and healthcare delivery.
Factors and preferences that influence treatment decision-making for patients, carers and clinicians regarding adjuvant immunotherapy [Chapters 3–5]
Three studies established the concepts instrumental in immunotherapy decision-making. First, a systematic review of the factors melanoma patients and their clinicians considered in immunotherapy decisions revealed that overall survival was of primary importance, followed by impaired quality of life due to toxicity. Second, patient and carer focus groups revealed influential aspects for immunotherapy, including living longer, toxicity, out-of-pocket [OOP] costs and uncertainty about efficacy. Third, interviews with melanoma clinicians highlighted that the disease sub-stage and treatment benefits versus risks drove their treatment recommendations.
Preferences and trade-offs for adjuvant immunotherapy among patients with resected stage III melanoma [Chapter 6]
One hundred and sixteen patients completed a discrete choice experiment [DCE] with two treatment options—adjuvant immunotherapy or observation without adjuvant immunotherapy. Three-quarters of the sample chose immunotherapy. The DCE included six attributes: chance of reducing melanoma recurrence; mild, permanent, or fatal adverse events [AEs]; annual OOP costs; and drug regimen. Immunotherapy was preferred if the absolute risk reduction for recurrence and the chance of fatal AEs were lower. Patients accepted a 4% increase in the chance of a permanent AE to reduce their risk of 3-year recurrence by 1%.
Conclusions
Treatment features, including reduced risk of melanoma recurrence, reduced chance of permanent and fatal AEs, and decreased yearly OOP costs, positively influenced the choice for adjuvant immunotherapy. Understanding patient preferences facilitates the alignment of healthcare policies to improve health outcomes for people with resected stage III melanoma.
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Motala, Ismail Mohammed, and Saartjie Roux. "Formulation of an optimal non-targeted liposome preparation for fusion with tumour cell line membranes." Thesis, Nelson Mandela Metropolitan University, 2016. http://hdl.handle.net/10948/12220.
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The most common treatment used for cancer is chemotherapy. Chemotherapeutic agents have a greater affinity for rapidly dividing cells which is a characteristic of tumour cells. Although anti-cancer agents have their advantages in providing anti-cancer effects, they can be seen as highly toxic molecules posing a threat to normal healthy tissue within the human body. However, these toxic therapies need to be delivered to tumour sites without damaging healthy tissue. Liposomes can serve as a delivery system for these toxic molecules and be delivered to the tumour site via the EPR effect. Hence, liposomes that fuse with tumour cell line membranes are advantageous in delivering payloads of drugs directly into the tumour cell without damaging normal healthy tissue. The aim of the study was to formulate an optimised liposome preparation in order to enhance cellular uptake by MCF-7, Caco-2 and C3A cancer cell lines via membrane fusion. The optimal liposome formulation was aimed to be prepared utilising a statistical design approach in order to determine the ranges of the parameters that were furthermost optimal in formulating an ideal liposome preparation. The primary screening design was conducted using a 24-1 fractional factorial design that took into account the four parameters that were used to determine the optimisation of the liposomal preparation. The four variables used in the liposome preparation were the phospholipid type (PS or DOPE), the concentration of cholesteryl hemisuccinate (CHEMS) (10 – 40 %), the concentration of PEG2000-PE (0.5 – 4 %) and liposome size (100 or 200 nm). Liposomes were prepared using thin film hydration method and characterisation for size and zeta potential was carried out using photon correlation spectroscopy (PCS). Visual characterisation of liposome size was carried out using atomic force microscopy (AFM). Liposomes were exposed the cancer cell lines with visualisation and uptake being measured using fluorescent microscopy and flow cytometry, respectively. An optimal liposome preparation was prepared following the statistical design method. The optimal liposome preparation consisted of phospholipid type PS, 22.91 % of CHEMS, 4 % of PEG2000-PE and a liposome size of 200 nm. AFM analysis has shown that optimal liposome sizes ranged between 130 and 170 nm. Flow cytometry analysis indicated high level of liposome uptake with actual values falling below the predicted values set out by the statistical design. Fluorescence microscopy captured images of the fluorescent liposomes concentrated on the membrane of cells. The objective of the study was to determine from literature which variables would be desirable in preparing an optimal non-targeted liposome preparation. This was achieved by identifying four such variables and utilising them in a statistical design approach which was screened in order to determine the ideal parameters in preparing the optimised liposome batch. Therefore, from the results obtained it can be concluded that the aim of the study were met by preparing an optimal liposome preparation that has the ability to fuse with the tumour cell line membranes.
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Ahnström, Waltersson Marie. "Cell cycle alterations and 11q13 amplification in breast cancer : prediction of adjuvant treatment response." Doctoral thesis, Linköpings universitet, Onkologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-17458.
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The growth and development of the breast is to a large extent regulated by oestrogens through the oestrogen receptor (ER). Activation of the ERα triggers transcription of genes that are important for cell proliferation and stimulates entry into the G1 phase of the cell cycle. In breast cancer the ERα is often upregulated and is therefore a suitable target for adjuvant therapies such as tamoxifen. Although tamoxifen is an effective treatment in most cases, tumours sometimes acquire resistance to the drug. The aim of this thesis was to investigate the impact of G1 phase proteins and 11q13 amplification on prognosis and treatment response in breast cancer. The material used was from a clinical trial in which postmenopausal breast cancer patients were randomised to chemotherapy or radiotherapy and tamoxifen or no adjuvant treatment. We studied the expression of cyclin D1, cyclin E and Rb with immunohisochemistry and amplification of CCND1 and PAK1 with real time PCR. We found that among patients with high tumour expression of cyclin D1, overexpression of ErbB2 was associated with reduced recurrence-free survival. Both cyclin D1 and cyclin E overexpression were associated with reduced tamoxifen response. High expression of cyclin D1 has been found to induce ligand independent activation of ERα in breast cancer cells and might also switch tamoxifen from acting as an antagonist to an agonist. Overexpression of cyclin E has been shown to be associated with expression of low molecular weight isoforms of the protein that possess an increased kinase activity and are insensitive to p21 and p27 inhibition. Furthermore, amplification of 11q13, and in particular the gene PAK1, was a strong predictor of tamoxifen resistance. The pak1 protein is involved in phosphorylation and ligand independent activation of the ERα. We also found that lost expression of either p53 or Rb reduced the patients benefit from radiotherapy compared with patients with normal expression of both proteins. Normally, ionizing radiation upregulates p53 resulting in G1 arrest or apoptosis. If either functional p53 or Rb is missing the cells can proceed from G1 to the S phase despite damaged DNA. The expression of the microRNA, miR-206, was analysed with real time PCR, and the results showed that high expression of miR-206 correlated to low expression of ERα and 11q13 amplification. In vitro studies have shown that miR-206 negatively regulates the expression of ERα. Taken together the G1 regulators and amplification of 11q13 seem to have an important role in predicting the patient’s response to adjuvant therapy.
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Glangkarn, Sumattana. "Quality of life in Thai women with early-stage breast cancer during adjuvant treatment." Thesis, University of Nottingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523086.
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Coyle, C. "Repurposing medicines for the adjuvant treatment of cancer : an evaluation of aspirin and metformin." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10050892/.
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Introduction: Evidence from pre-clinical studies and observational data suggest that metformin and aspirin are good candidates for adjuvant therapies, though definitive phase III trials have not been completed. Prior to the initiation of this work, the Add-Aspirin trial had been conceived and funded with several potential challenges related to the implementation and design identified. Evidence to support the evaluation of metformin in a phase III adjuvant basket trial had not been systematically evaluated. Methods: I examined the implementation and conduct of the Add-Aspirin trial during its first year at individual UK research centres. Baseline clinical characteristics, and the feasibility and effect of the run-in period, in the first 500 participants was also examined. Additionally, I conducted a systematic review and meta-analysis to investigate the effect of metformin use on survival outcomes for individual tumour types in the adjuvant setting. Results: Centres recognised the efficiencies offered from a basket trial design particularly in terms of gaining approvals, staffing and data entry, though some unanticipated set-up and recruitment challenges have been identified. The baseline clinical characteristics were largely as expected. Overall, 88% of participants were randomised. The run-in period was effective in identifying, and preventing randomisation of participants who had less than 80% adherence (5.0%), and participants who developed significant aspirin related toxicities (1.2%). Other nonrandomisations were mostly due to minor toxicity and/or personal choice. A systematic review and meta-analysis found that metformin use was associated with significant benefits in recurrence-free survival, overall survival and cancer-specific survival in early-stage colorectal and prostate cancer. Conclusion: Opening a large multi-tumour type basket trial with an active run-in period was found to be feasible, but minor conduct modifications have been recommended and protocol amendments implemented. Metformin could be a useful adjuvant agent, and randomised control trials in colorectal and prostate cancer are advocated.
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Pérez-Tenorio, Gizeh. "Alterations in the PI3K/AKT Signaling Pathway and Response to Adjuvant Treatment in Breast Cancer." Doctoral thesis, Linköpings universitet, Onkologi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-15043.
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(PI3K)/AKT signaling pathway could be a cause of therapeutic resistance in breast cancer. The PI3K/AKT pathway controls cell proliferation, cell growth and survival, and its members include oncogenes and tumor suppressor genes. Alterations in this pathway are frequent in cancer. In this thesis, we aimed to study the biological significance of some of these alterations in a tumor context as well as their clinical value. PIK3CA gene, encoding the PI3K catalytic subunit, was examined for mutations. The tumor suppressor PTEN, that counteracts PI3Kmediated effects, was studied at the protein level whereas amplification of RPS6KB1 (S6K1) and RPS6KB2 (S6K2) genes, encoding two substrates of the mammalian target of rapamycin (mTOR) acting downstream PI3K/AKT, was also inspected. AKT phosphorylation or activation (pAKT) was determined by immunohistochemistry. Other factors related with this pathway, such as HER-2, heregulin (HRG) β1, the cell cycle inhibitor p21WAF1/CIP1, the pro-apoptotic factor Bcl-2, and cyclin D1, were also considered. These studies were perfomed in two patient materials consisting of premenopausal patients that received endocrine treatment (paper I) and postmenopausal patients randomized to receive radiotherapy (RT) or chemotherapy (CMF) in combination with tamoxifen (Tam) or no endocrine treatment (papers II-IV). In the first material, we found that pAKT indicated higher risk of distant recurrence among endocrine treated patients. In the second material HRGβ1 induced accumulation cytoplasmic p21 in vitro and pAKT was associated with cytoplasmic p21 in the tumors. In addition, p21 cellular location identified subgroups of ER+ patients with different responses to tamoxifen. Other alterations such as PIK3CA mutations and PTEN loss were positively associated in this material. PIK3CA mutations lowered the risk for local recurrences while PTEN loss conferred radiosensitivity as a single variable or combined with mutated PIK3CA. PIK3CA mutations and/or PTEN loss was associated with lower S-phase (SPF). Nevertheless, among patients with low proliferating tumors, these alterations predicted higher risk of recurrence in contrast to those with high proliferating tumors. Finally, we found amplification of the S6K1 and S6K2 genes. S6K2 amplification was associated with cyclin D1 gene amplification, predicted poor recurrence-free survival and breast cancer death, and indicated benefit from tamoxifen. On the other hand, S6K1 amplification was associated with HER-2 amplification/overexpression, indicated higher risk of recurrence and was a predictor of poor response to radiotherapy. These results indicate the potential of this pathway as therapeutic source.Bröstcancer är en vanlig sjukdom och dödsorsak bland kvinnor i Sverige. Könshormonet östrogen tillsammas med cellernas receptorer för hormonet spelar en viktig roll för bröstcancerutvecklingen. Därför behandlas denna sjukdom med anti-hormonella substanser inriktade mot hämning av östrogensyntes/östrogen receptorn. Tamoxifen är den vanligaste formen av anti-östrogenbehandling som används efter operation. Tamoxifenbehandling förbättrar betydligt 5-årsöverlevnaden hos patienter med östrogenreceptorpositiva tumörer. Emellertid finns det patienter som återkommer med metastaser efter en tid. I det här projektet studerar vi andra receptorer samt deras signalvägar som kan aktivera östrogenreceptorn och därmed orsaka tamoxifenresistens. En sådan receptor är HER-2 vilken överuttrycks i 15-20% vid bröstumörer. HER-2 receptorn kan rekrytera proteiner med enzymatisk aktivitet, till exempel PI3K. PI3K aktiverar ett annat enzym, AKT, vilket är inblandat i en kaskad som leder till tumörtillväxt och tumöröverlevnad (genom till exempel aktivering av östrogenreceptorn). Våra resultat hitills visar att patienter med aktiverat AKT (pAKT) har större risk att få metastaser och därmed sämre överlevnad än patienter utan pAKT, detta trots hormonell behandling. I större material där HER-2 proteinuttrycket korrelerar med pAKT har vi också funnit att patienter med AKTnegativa tumörer kunde dra nytta av både tamoxifen och strålbehandling. Vi har även undersökt PIK3CA genen (som kodar för en del av PI3K) och hittat mutationer i 24% av bröstumörerna. Det är dock ännu oklart hur dessa mutationer ska tas hänsyn till för att kunna bestämma en effektiv behandling. PTEN är ett annat enzym som motverkar PI3K-aktivitet. Bortfall av PTEN förekommer ofta i bröstcancer och har associerats med PI3K/AKT aktivering. I vårt material var PTEN-förlust frekvent (37%) och associerades med PIK3CA mutationer. PTEN förlust som ensam faktor eller tillsammans med PIK3CA mutationer ökade strålkänslighet. Andra proteiner som är inblandade i PI3K signalvägen är S6K1 och S6K2 och dessa har betydelse för cellens proteinsyntes. Nyligen har vi kunnat visa att generna för både S6K1/2 finns i många kopior (genamplifering) I tumörcellerna hos bröstcancerpatienter. Dessutom fanns det ett positivt samband mellan S6K1/2 amplifiering och amplifiering av andra kända cancergener (som t. ex HER-2 och cyclin D1) men förhållandet till PIK3CA-mutationer var det omvända. Patienter med antigen S6K1 eller HER-2 amplifierade tumörer svarade dåligt på strålbehandling men skulle möjligen kunna behandlas med en specifik substans riktad mot S6K1 eller HER-2. Ett ökat antal kopior av S6K2 indikerade dålig prognos men bra nytta av tamoxifen. Våra resultat visar att PI3K/AKT signalvägen ofta är aktiverad vid bröstcancer och skulle kunna vara en viktig måltavla för behandling.
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Morris, Brenda Carol 1965. "Relationship between symptom distress and life quality in women with breast cancer undergoing adjuvant treatment." Thesis, The University of Arizona, 1991. http://hdl.handle.net/10150/558158.
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Best, Jennie H. "Preference values for health states associated with colon cancer and its treatment /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/7932.
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Kesler, Megan Kathleen. "Mitigation of Undesirable Flavor in Kefir Intended for Adjuvant Treatment of Clostridioides difficile Infection." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1565357220348372.
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Brand, Juanita M. "The lived experiences of six women during adjuvant chemotherapy for Stage I or II breast cancer." Virtual Press, 2005. http://liblink.bsu.edu/uhtbin/catkey/1317926.
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Kerrigan, Matthew Charles. "Treatment patterns, costs and outcomes of systemic chemotherapy, adjuvant intravesical therapy, and surveillance for urothelial bladder cancer /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/7949.
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MACAIONE, Ina. "Intraperitoneal chemotherapy versus adjuvant chemotherapy for treatment of colo-rectal cancer at high-risk for peritoneal carcinosis." Doctoral thesis, Università degli Studi di Palermo, 2021. http://hdl.handle.net/10447/506907.
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Hellerstedt-Börjesson, Susanne. "Smärta vid adjuvant cytostatikabehandling : Uppfattningar och inverkan på dagligt liv hoskvinnor diagnostiserade med bröstcancer." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156063.
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Featured adjuvant chemotherapy treatment in women with breast cancer can lead to pain. The aim of this study was to explore, the variety of perceptions and impact of adjuvantchemotherapy-induced pain in daily life, of some women newly diagnosed with breast cancer.Inclusion criteria were participating in an ongoing stress management projectand chemotherapy of (anthracycline/taxan) in doses of 75mg² or more. Exclusioncriteria were inability to understand and communicate in Swedish and mentalillness. After ethical approval of the sub study in September 2010, women wereconsecutively included through oral and written request. Phenomenologicalapproach was used in the eight interviews and data analysis. The resultconsisted of five categories of description, the obvious pain, themanageable pain, the lonely pain, the unimaginable pain andultimately the crippling pain. The existence was open when the pain feltdescribable and manageable, while it was concluded when the pain seemedinexplicable and life drastically changed. The study showed a significantpainful impact of chemotherapy. The woman had difficulties to refer to theinformation given by the medical services, when the pain went beyond previousexperiences. There was a tendency that the woman waited before she contactedthe medical services, this waiting made room for difficult thoughts andfeelings. A question for further research is how the staff can capture andbetter help the women who experience severe pain.Dagens adjuvanta cytostatikabehandlingav kvinnor med bröstcancer kan leda till smärta. Denna studies syfte var att undersöka olikauppfattningar om inverkan av smärta, utlöst av adjuvant cytostatikabehandling,på dagligt liv hos några kvinnor som nyligen diagnostiserats med bröstcancer.Inklusionskriterier var deltagande i ett pågående stresshanteringsprojekt ochcytostatikabehandling i doser om 75mg² eller mer av antracyklin och/ellertaxan. Exklusionskriterier var oförmåga att förstå och kommunicera på svenska ochpsykisk sjukdom. Efter etiskt godkännande av delstudien i september 2010 inkluderades kvinnorna konsekutivt genommuntlig och skriftlig förfrågan. Fenomenologisk ansats användes i de åttaintervjuerna och i resultatbearbetningen. Resultatet kom att utgöras av fembeskrivningskategorier: den förklarliga smärtan, den övervinneliga smärtan, denensamma smärtan, den ofattbara smärtan och sist den förlamande smärtan.Tillvaron var öppen då smärtankändes förklarbar och därmed hanterbar, medan den slöts när smärtan kändesoförklarlig och kvinnornas liv förändrades drastiskt. Studien visar på en betydande smärtinverkan vid cytostatikabehandling. Kvinnornafick svårt att referera till den av sjukvården givna informationen, när smärtangick utanför tidigare beskrivning och smärtupplevelser. Det fanns en tendensatt kvinnan avvaktade innan hon kontaktade sjukvården och i denna väntanuppstod svåra tankar och känslor. En fråga för vidare forskning är hurpersonalen kan fånga upp och bättre hjälpa de kvinnor som får svåra smärtor.
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Sereni, Maria Isabella, Elisa Baldelli, Guido Gambara, Antonella Ravaggi, K. Alex Hodge, David S. Alberts, Jose M. Guillen-Rodriguez, et al. "Kinase-driven metabolic signalling as a predictor of response to carboplatin–paclitaxel adjuvant treatment in advanced ovarian cancers." NATURE PUBLISHING GROUP, 2017. http://hdl.handle.net/10150/625488.
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Background: The biological mechanisms underlying early-and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. Methods: Tumour epithelia were isolated from two independent sets of primary EOC (n-72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection. Reverse phase protein microarrays were used to broadly profile the kinase-driven metabolic signalling of EOC with particular emphasis on the LBK1-AMPK and AKT-mTOR axes. Signalling activation was compared between early and advanced lesions, and carboplatin-paclitaxel-sensitive and -resistant tumours. Results: Advanced EOCs were characterised by a heterogeneous kinase-driven metabolic signature and decreased phosphorylation of the AMPK-AKT-mTOR axis compared to early EOC (P<0.05 for AMPK alpha T172, AMPK alpha 1 S485, AMPK beta 1 S108, AKT S473 and T308, mTOR S2448, p70S6 S371, 4EBP1 S65, GSK-3 alpha/beta S21/9, FOXO1 T24/FOXO3 T32, and FOXO1 S256). Advanced tumours with low relative activation of the metabolic signature and increased FOXO1 T24/FOXO3 T32 phosphorylation (P=0.041) were associated with carboplatin-paclitaxel resistance. Conclusions: If validated in a larger cohort of patients, the decreased AMPK-AKT-mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin-paclitaxel-resistant EOC patients.
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Thewes, Belinda Public Health & Community Medicine Faculty of Medicine UNSW. "The fertility-and menopause-related information needs of young women with a diagnosis of early-stage breast cancer." Awarded by:University of New South Wales. School of Public Health and Community Medicine, 2006. http://handle.unsw.edu.au/1959.4/25212.
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Background: The use of chemotherapy and endocrine therapies in the treatment of pre-menopausal women with breast cancer may result in menopausal symptoms, permanent infertility or the need to delay pregnancy. This series of studies investigates the fertility- and menopause-related information needs of pre-menopausal women with a diagnosis of early breast cancer (Studies 1 and 2) and the benefits women need to make undergoing adjuvant endocrine therapies worthwhile (Study 3). Method: Study 1 is a qualitative study of 24 women and Study 2 a survey study amongst 228 women. Study 3 included a subset of 102 women from the sample involved in Study 2 who had been treated with endocrine therapies for a minimum of three months. To be eligible, women had to be aged 40 years or younger (Study 2 and 3) when diagnosed with early stage breast cancer, and be 6-60 months post-diagnosis at the time of participation. For Study 2, participants completed a mailed self-report questionnaire that included a fertility- and menopause-related information needs survey, and standardized measures of distress, quality-of-life, menopausal symptoms and information preferences. For Study 3, participants were asked to complete a face-to-face interview. Results: Study 1 showed that many women thought that the information they had received in the past about fertility and menopausal symptoms was either insufficient or unavailable. Some women felt that, while information on fertility and menopause issues had not been paramount at the time of diagnosis, it became increasingly important after diagnosis. Study 2 showed that 71% of participants discussed fertility-related issues with a health professional as part of their breast cancer treatment and 86% discussed menopause-related issues. Consultation with a fertility or menopause specialist was the most preferred method of obtaining this information. Study 3 demonstrated that the majority of participants considered adjuvant endocrine therapy worthwhile for a 2% absolute gain in survival rates and for a 6-month gain in life expectancy. Conclusions: The results of this series of studies suggest that younger women have unmet needs for fertility- and menopause-related information. Women with early breast cancer who had received adjuvant endocrine therapies judged modest survival gains sufficient to make adjuvant endocrine therapy worthwhile.
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Ali, Dulfikar A. "The feasibility of exercise in low and high grade glioma patients during radiation with or without adjuvant chemotherapy." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/233465/1/Dulfikar_Ali_Thesis.pdf.
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This research was a longitudinal mixed methods study that involved the delivery of an exercise intervention in brain cancer patients undergoing treatment. Three studies were conducted to examine post-surgical functioning, feasibility and safety, and a qualitative review of patients’ acceptability and experiences.
This research highlighted functional deficits after surgery, limiting independence. The delivery of an exercise intervention during treatment is both feasible and safe. Clinically important improvements in aerobic functioning, lower-body strength and mobility were observed after cancer treatment. Participating in the exercise intervention provided patients with respite from their cancer journey and promoted positive coping ability towards future outlook.
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Ishtayeh, Bilal. "Dexamethasone as adjuvant treatment in patients with acute severe pharyngitis : a descriptive study at Welcare Hospital emergency unit, Dubai, United Arab Emirates." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/98212.
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Thesis (MFamMed)--Stellenbosch University, 2015.Background: An increased incidence of acute group A ß-hemolytic Streptococcal (GABHS) pharyngitis has been reported anecdotally at the Welcare Hospital in Dubai. Aim: To describe the outcomes of patients with acute GABHS pharyngitis who received standard therapy at the Welcare hospital emergency unit in Dubai. Objectives To determine the time elapsed before patients experience a clinically significant reduction in pain. To describe the side-effect profile of standard treatment received for acute GABHS pharyngitis. Methods: This is a cross-sectional study design. Consecutive sampling of 123 patients was done from December, 2013 to March, 2014. A questionnaire was used to record demographic data and severity of GABHS before patients received standard treatment. The Visual Analogue Scale (VAS) was used to measure pain severity at baseline and during follow-up. Adults diagnosed with GABHS pharyngitis who received dexamethasone as part of standard treatment offered were included. Results: Clinical pain relief, which was suggested as a VAS score of 4, was achieved by 5.7% of the patients at 12 hours. At 24 hours, 55.3% of the patients reported a VAS score of 4. The mean VAS score of the patients at this time was 4.12. A total of 99.2% of the patients reported a VAS score of 4 or lower at 36 and 48 hours. Paired t-test revealed statistically significant difference between the VAS scores at 12, 24, 36 and 48 hours and baseline (p=0.000). This suggests that clinical pain relief was achieved by 55.3% of the patients at 24 hours. At 48 hours, 21.1% of the patients reported a VAS score of 0. None of the patients reported any side effects associated with the one dose use of dexamethasone. Conclusion: The findings suggest that dexamethasone is safe and effective to use as adjuvant for management of pain associated with acute GABHS pharyngitis. Almost all patients experienced significant pain relief by 36 and 48 hours and no side-effects related to dexamethasone use were recorded. Further definitive randomised controlled trials are needed to establish these findings as evidence for practice.
AFRIKAANSE OPSOMMING: Nie beskikbaar
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Hakenberg, Oliver W., H. J. Franke, Michael Fröhner, and Manfred P. Wirth. "The Treatment of Primary Urethral Carcinoma – the Dilemmas of a Rare Condition: Experience with Partial Urethrectomy and Adjuvant Chemotherapy." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135145.
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Background: Primary urethral carcinoma is a very rare condition, and no large-scale experience with such cases has been published. Treatment will therefore have to follow rules established for the treatment of similar conditions. Patients: Six cases of primary urethral carcinoma (5 male, 1 female) who had been treated at our institution between 1995 and 1999 were retrospectively analyzed. In 3 male cases, a primary urothelial carcinoma of the distal urethra was treated by distal urethrectomy only. In 3 other cases with locally advanced tumors and/or lymph node metastases surgical treatment was followed by adjuvant cisplatinum-containing chemotherapy. Results: In the 3 cases with distal urethral carcinoma, partial urethrectomy with preservation of the penis resulted in cure, with a follow-up of 12–71 months. In the cases with advanced disease, adjuvant chemotherapy after surgery has resulted in complete remissions in all 3 cases, with a follow-up of 4–47 months at present. Conclusions: In localized, noninvasive carcinoma of the distal male urethra, partial urethrectomy seems adequate and the avoidance of penile amputation justified. In advanced cases, after local excision and lymphadenectomy adjuvant chemotherapy which by necessity must follow the guidelines established for the treatment of other urothelial or squamous cell malignancies seems to be beneficialHintergrund: Das primäre Harnröhrenkarzinom ist eine sehr seltene Erkrankung, und in der Literatur gibt es keine prospektiven Serien mit größeren Fallzahlen. Die Behandlung wird sich daher an Erfahrungen orientieren müssen, die bei der Behandlung ähnlicher Krankheitsbilder gewonnen wurden. Patienten: Sechs Fälle von primärem Urethralkarzinom (5 Männer, 1 Frau), die zwischen 1995 und 1999 in unserer Klinik behandelt wurden, wurden retrospektiv analysiert. Bei 3 der männlichen Patienten lag ein primäres Urothelkarzinom der distalen Harnröhre vor, und es wurde eine Urethrateilresektion ohne adjuvante Therapie durchgeführt. In den 3 anderen Fällen mit lokal fortgeschrittenen Tumoren und/oder Lymphknotenbefall wurde nach operativer Behandlung eine adjuvante Cisplatin-haltige Chemotherapie durchgeführt. Ergebnisse: In allen 3 Fällen nach Urethrateilresektion wurde eine komplette Heilung bei einer Nachbeobachtung von 12–71 Monaten erzielt. Bei den fortgeschrittenen Fällen mit lymphogener Metastasierung wurde nach adjuvanter Chemotherapie in allen 3 Fällen eine komplette Remission bei einer Nachbeobachtung von bislang 4–47 Monaten erzielt. Schlußfolgerungen: Beim lokalisierten, nichtinvasiven distalen Urethralkarzinom des Mannes ist eine organerhaltende Strategie gerechtfertigt. In lokal fortgeschrittenen und/oder lymphogen metastasierten Fällen ist nach lokaler Exzision und Lymphadenektomie eine adjuvante Chemotherapie, die sich an den Erfahrungen der Behandlung von anderen Plattenepithel- und Urothelkarzinomen orientieren muß, sinnvoll und erfolgversprechend
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Filho, Supercilio Barros. "Endodontic treatment of teeth with periapical lesion in one session with photodynamic therapy as an adjuvant: study "in vivo"." Universidade de Taubaté, 2012. http://www.bdtd.unitau.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=409.
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Hypothesis of the study: It is assumed that the use of photodynamic therapy (PDT) as an adjuvant in root canal therapy can promote the repair of teeth with periapical lesions treated in one session. Objectives: This in vivo study was to evaluate the effects of photodynamic therapy as an adjuvant in root canal therapy in one session for the repair of periapical lesions. Method: Fourteen human teeth with mortification pulp and periapical lesions were randomly divided into two groups (n=7): G1- endodontic treatment was performed in one session and G2 underwent endodontic therapy in one session associated with photodynamic therapy. The photodynamic therapy used methylene blue dye (100μ/mL) for five minutes and diode laser low power (685nm, 100mW) for three minutes. The follow-ups were performed by periapical radiographs. The images were evaluated by the computer program Adobe Photoshop CS 5.1, using the system K values. By which we assessed the area of periapical bone healing. Radiographs were taken prior to execution, immediately after treatment, and six months following the treatment. Results: There were statistically significant differences between the G2- endodontic therapy in one session associated with photodynamic therapy and G1- endodontic therapy in one session (p<0.05) without PDT. Conclusion: The endodontic treatment in one session associated with photodynamic therapy was more effective in repair of the periapical lesion.Hipótese do estudo: O emprego da terapia fotodinâmica (PDT) como coadjuvante do tratamento endodôntico possa favorecer a reparação de dentes portadores de lesão periapical, tratados em sessão única. Objetivos: Este estudo in vivo, teve por objetivo avaliar, os efeitos da terapia fotodinâmica como coadjuvante do tratamento endodôntico em sessão única, na reparação de lesões periapicais. Método: Quatorze dentes humanos portadores de mortificação pulpar e lesão periapical, foram aleatoriamente divididos em dois grupos (n=7): G1- foi realizado tratamento endodôntico em sessão única, G2- foi submetido à terapia endodôntica em sessão única, associado à terapia fotodinâmica. Para a terapia fotodinâmica utilizou-se como corante o azul de metileno (100μ/mL) por cinco minutos e o laser de diodo de baixa potência (685nm, 100mW) por três minutos. A proservação foi realizada por meio de radiografias periapicais. As imagens foram avaliadas por um programa de computador Adobe Photoshop CS 5.1, valendo-se dos valores médios de K. Pelo qual foi avaliado a área de cicatrização óssea periapical. As radiografias foram tomadas antes da execução do tratamento endodôntico, imediatamente após e proservado com cento e oitenta dias após o tratamento. Resultados: Houve diferença estatísticamente significante entre o grupo G2- terapia endodôntica em sessão única associado à terapia fotodinâmica e G1- terapia endodôntica em sessão única (p< 0,05). Conclusão: O tratamento endodôntico em sessão única associado à terapia fotodinâmica mostrou-se mais eficaz na reparação da lesão periapical.
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Hakenberg, Oliver W., H. J. Franke, Michael Fröhner, and Manfred P. Wirth. "The Treatment of Primary Urethral Carcinoma – the Dilemmas of a Rare Condition: Experience with Partial Urethrectomy and Adjuvant Chemotherapy." Karger, 2001. https://tud.qucosa.de/id/qucosa%3A27623.
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Background: Primary urethral carcinoma is a very rare condition, and no large-scale experience with such cases has been published. Treatment will therefore have to follow rules established for the treatment of similar conditions. Patients: Six cases of primary urethral carcinoma (5 male, 1 female) who had been treated at our institution between 1995 and 1999 were retrospectively analyzed. In 3 male cases, a primary urothelial carcinoma of the distal urethra was treated by distal urethrectomy only. In 3 other cases with locally advanced tumors and/or lymph node metastases surgical treatment was followed by adjuvant cisplatinum-containing chemotherapy. Results: In the 3 cases with distal urethral carcinoma, partial urethrectomy with preservation of the penis resulted in cure, with a follow-up of 12–71 months. In the cases with advanced disease, adjuvant chemotherapy after surgery has resulted in complete remissions in all 3 cases, with a follow-up of 4–47 months at present. Conclusions: In localized, noninvasive carcinoma of the distal male urethra, partial urethrectomy seems adequate and the avoidance of penile amputation justified. In advanced cases, after local excision and lymphadenectomy adjuvant chemotherapy which by necessity must follow the guidelines established for the treatment of other urothelial or squamous cell malignancies seems to be beneficial.Hintergrund: Das primäre Harnröhrenkarzinom ist eine sehr seltene Erkrankung, und in der Literatur gibt es keine prospektiven Serien mit größeren Fallzahlen. Die Behandlung wird sich daher an Erfahrungen orientieren müssen, die bei der Behandlung ähnlicher Krankheitsbilder gewonnen wurden. Patienten: Sechs Fälle von primärem Urethralkarzinom (5 Männer, 1 Frau), die zwischen 1995 und 1999 in unserer Klinik behandelt wurden, wurden retrospektiv analysiert. Bei 3 der männlichen Patienten lag ein primäres Urothelkarzinom der distalen Harnröhre vor, und es wurde eine Urethrateilresektion ohne adjuvante Therapie durchgeführt. In den 3 anderen Fällen mit lokal fortgeschrittenen Tumoren und/oder Lymphknotenbefall wurde nach operativer Behandlung eine adjuvante Cisplatin-haltige Chemotherapie durchgeführt. Ergebnisse: In allen 3 Fällen nach Urethrateilresektion wurde eine komplette Heilung bei einer Nachbeobachtung von 12–71 Monaten erzielt. Bei den fortgeschrittenen Fällen mit lymphogener Metastasierung wurde nach adjuvanter Chemotherapie in allen 3 Fällen eine komplette Remission bei einer Nachbeobachtung von bislang 4–47 Monaten erzielt. Schlußfolgerungen: Beim lokalisierten, nichtinvasiven distalen Urethralkarzinom des Mannes ist eine organerhaltende Strategie gerechtfertigt. In lokal fortgeschrittenen und/oder lymphogen metastasierten Fällen ist nach lokaler Exzision und Lymphadenektomie eine adjuvante Chemotherapie, die sich an den Erfahrungen der Behandlung von anderen Plattenepithel- und Urothelkarzinomen orientieren muß, sinnvoll und erfolgversprechend.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Asaria, Riaz Hassan Yusuf. "Proliferative vitreoretinopathy : the use of adjuvant therapy in the treatment of patients and the study of clinical & biological risk factors." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397951.
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Thornton, Michael. "The 78 kDa glucose regulated protein (GRP78) as a potential treatment predictive biomarker and therapeutic target in colorectal cancer adjuvant chemotherapy." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/17993/.
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Introduction: Glucose-regulated protein 78-kDa (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone that is essential for correct protein folding and assembly in the ER lumen. Micro-environmental stress and a requirement for increased protein synthesis, typical of solid tumours, leads to a disruption of ER homeostasis, and accumulation of misfolded proteins. The ability of GRP78 to dissociate from several important ER-resident transmembrane proteins under conditions of ER stress leads to a cascade of signal transduction pathways, known as the unfolded protein response (UPR), that modulate cell survival or, if the stress is significantly severe, apoptosis. GRP78 has been found to be overexpressed in a variety of cancers compared with benign tissue and has been associated with poor outcome. In-vitro data indicate that GRP78 expression is often associated with aggressive phenotype and drug resistance. Thus, GRP78 has potential as a biomarker for tumour behaviour and treatment response. For stage III colorectal cancer, there is overwhelming evidence to recommend the use of fluoropyrimidine-based adjuvant chemotherapy. Unfortunately, a large proportion of patients do not benefit from adjuvant chemotherapy, and biomarkers that can determine the likelihood of response to chemotherapy remain elusive. The benefit of chemotherapy in stage II disease is less certain and markers that could reliably predict benefit would be particularly useful in this population. This study explores a potential mechanistic relationship between GRP78 and 5-FU sensitivity using both siRNA transfection and treatment with an engineered fusion protein, epidermal growth factor (EGF)-SubA, which has been demonstrated to cause highly selective cleavage of GRP78 at a single amino acid point. It was then examined whether GRP78 may have prognostic or predictive value in the context of colorectal cancer patients treated with fluoropyrimidine-based chemotherapy. The potential therapeutic value of targeting GRP78 in vitro using EGF-SubA is also examined. Methods: Colon cancer cell lines were used to examine response to 5-FU upon modulation of endogenous GRP78 using siRNA technology and EGF-SubA. Apoptosis and cell cycle progression were assessed using flow cytometry. Immunohistochemistry was used to characterise GRP78 expression in a large cohort of colorectal cancers on tissue microarrays and the results were correlated with clinicopathological parameters and with 5-year survival for the whole cohort and those treated with fluoropyrimidine-based (5-FU) adjuvant chemotherapy. The action of EGF-SubA upon colon cancer cells was examined using western blotting, MTT assay and flow cytometry. Results: GRP78 promotes apoptosis in response to 5-FU. Better overall 5-year survival was associated with high GRP78 expression (P=0.036). Stage III patients with high GRP78 showed significant benefit from adjuvant chemotherapy (P=0.026), whereas patients with low GRP78 failed to benefit (P=0.805). Low GRP78 was an independent poor prognostic indicator of overall 5-year survival (P=0.005; HR=1.536; 95%CI 1.139-2.122). Colon cancer cells expressing EGFR were highly sensitive to EGF-SubA, demonstrating reduced proliferation and cell cycle arrest. However, EGF-SubA did not induce significant apoptosis and reduced the effectiveness of 5-FU in vitro. Conclusion: This study demonstrates a mechanistic relationship between GRP78 expression and response to 5-FU. GRP78 expression may provide a useful additional risk stratification to inform the adjuvant treatment of colorectal cancer. EGF-SubA does not have therapeutic value in colorectal cancer but is a useful tool for studying GRP78 and the UPR.
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Browall, Maria. "Experience of adjuvant treatment among postmenopausal women with breast cancer : health - related quality of life, symptom experience, stressful events and coping strategies /." Göteborg : Institute of Health and Care Sciences, Göteborg University, The Sahlgrenska Academy at Göteborg University, 2008. http://hdl.handle.net/2077/9586.
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Moore, Thomas B. "The Role of N-acetyl-L-Cysteine (NAC) as an Adjuvant to Opioid Treatment in Patients with Inadequately Controlled Chronic Neuropathic Pain." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4315.
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Introduction. While opioid medications are commonly prescribed for management of neuropathic pain (NP), long-term use has been associated with increased risk for overdose, drug interactions and addiction. New strategies are necessary to better manage chronic pain, thereby reducing need for opioid medications and their associated adverse consequences. N-acetyl-L-cysteine (NAC), an over-the-counter supplement, has shown promise in the treatment of psychiatric and addictive disorders. In addition, NAC has shown promise for reducing physiological signs of NP in laboratory rat models, prompting this study.
Purpose. The present study was an open-label clinical trial of NAC as an adjuvant to opioid treatment for poorly controlled, chronic NP. It examined whether 1200 mg NAC twice daily for 4 weeks was associated with: lower ratings of patient-reported pain; reductions in PRN opioid medication for breakthrough pain; and improvements in physical and mental health quality of life (QoL). The study also examined whether appraisal of pain impacts response to medication.
Method. Participants were N=28 chronic NP patients who consented to study participation. This consisted of 2 baseline assessments, 4 weeks of NAC and 1 post-trial follow-up visit. The majority (N=17) dropped out or were excluded during baseline. Of the remaining participants, N = 11 started the study medication and N=10 completed the study, with daily recordings of pain severity ratings and use of PRN opioid medication. Small sample size limited analyses to qualitative case reviews and effect sizes.
Results. Over 90% of participants receiving NAC completed the study. Case review found varied results. While 4 of 10 participants showed decrease in average pain ratings during NAC, estimated effect sizes for the whole sample were small, bordering on negligible (ω² from .003 to .027) as were those for PRN opioids (Partial Eta-Squared=.0003). Effect size for mental health QoL was medium (Cohen's d=.421).
Conclusions. With N=10, findings must be interpreted with caution. Nonetheless, the study found some albeit small evidence supporting NAC for improving mental health QoL and pain ratings. Several participants reported improvements in pain and mental health domains while taking NAC. NAC was well tolerated with minimal side effects. Lessons from this study will inform design and implementation of future NAC studies.
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McWhirter, Derek. "Defining the role of microRNA-122 in the early detection of chemotherapy-induced hepatotoxicity in the neo-adjuvant treatment of advanced colorectal cancer." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2007526/.
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Colorectal cancer remains one of the most common cancers in the United Kingdom with around 40,000 new cases being diagnosed each year. Around 25% of patients will have liver metastases at the time of presentation, with up to 50% developing metastases at some point in their life. Advances in surgical technique and developments in chemotherapy have increased the number of patients with advanced disease for whom potentially curative treatment is possible. The use of chemotherapy in a neo-adjuvant setting has improved the outcome for patients with liver metastases who have initially irresectable or borderline disease. Chemotherapy-induced hepatotoxicity affects up to 78% of patients receiving standard chemotherapy for colorectal cancer and can lead to increased morbidity and mortality. Current gold standard serum-based biomarkers of drug-induced hepatotoxicity have their limitations and there remains a need for more sensitive and specific novel biomarkers to detect early hepatotoxicity. The use of serum-based microRNAs, in particular microRNA-122 (miR-122), a hepatocyte-specific molecule has been proposed as a possible biomarker for chemotherapy-2induced hepatotoxicity. The work described in this thesis assessed the characteristics of serum miR-122 in a healthy human population. It also assessed serum levels of miR-122 in different diseases including primary liver cancer. In order to assess the role of serum miR-122 in chemotherapy-induced hepatotoxicity, a pilot study was carried out in patients receiving chemotherapy for advanced colorectal cancer. In a healthy human population (n=129) serum levels of miR-122 were measured to investigate the degree of variation and define a normal reference range that could be used to assess changes found in patients with hepatic injury and disease. In addition to miR-122, two endogenous (U6snRNA/let27d) and one exogenous controls (c.lin24) were measured. Inter-individual variation was low for miR-122 (CV% 5.21) and also for all three controls (CV% <4%). There was no circadian variation in serum miR-122 (ANOVA p=0.1254). Analysis of intra-patient variation over three consecutive days was similarly low (p=0.66). In a human population with underlying chronic liver disease (n=90) and primary liver cancer (n=104), serum miR-122 was significantly raised in the both cohorts (p=<0.001) but no difference was seen between the chronic disease and cancer cohorts (p=0.338). Patients with an underlying inflammatory condition had significantly raised serum miR-122 (p=<0.001) compared to those with underlying cirrhotic or fibrotic change (p=0.372). ROC analysis supported this finding (AUC 0.79 vs 0.54). In a pilot study of serum miR-122 during neo-adjuvant chemotherapy for colorectal cancer liver metastases, 11 patients were recruited. Serial blood sampling during chemotherapy treatment revealed a non-significant rise in miR-122 (p=0.14). Clinically insignificant levels of liver toxicity were seen in the ten patients who completed the treatment and had surgery. In those with histology changes known to be associated with chemotherapy, there was a significant rise in serum ALT (p=0.0082 and 0.0085) while the miR-122 did not rise significantly (p=0.053). This work confirmed the low variation in serum miR-122 that is a requirement for a novel biomarker. Furthermore, it confirmed the detectable increase of serum miR-122 in patients with liver disease, particularly those with an inflammatory pathophysiology. Finally, in a human model of chemotherapy-related hepatotoxicity, the role of miR-122 remains unclear at present, but the non-significant changes in level related to clinically insignificant liver perturbation compared to the significant changes in ALT suggest that, although more work is required, it may be a valuable biomarker with potential in this field.
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McSorley, Oonagh. "Health related quality of life and coping behaviours in men receiving radiotherapy and neo-adjuvant hormone treatment for prostate cancer: a quantitative longitudinal study." Thesis, Ulster University, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.669693.
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Men with localised prostate cancer can now expect to live longer with the disease and the side-effects of treatment than a decade ago. These side effects include urinary, bowel and sexual dysfunction which can affect their quality of life. Aim: There is a lack of information on how radiotherapy with neo-adjuvant hormone treatment affects men's quality of life over one year post-radiotherapy and how they cope with the disease and side-effects during this time. This study aims to address these gaps. Method: One hundred and forty-nine men who were about to undergo radiotherapy and neo-adjuvant hormone treatment for localised prostate cancer participated in this longitudinal study. They completed the EORTC QLQ C-30 & PR25 and the Brief Cope scale at four times (prior to radiotherapy, at four to six weeks post-radiotherapy; at six months and one year post-radiotherapy). The response rate was over 90% at each time-point. Results: Men reported the biggest decline in all aspects of health related quality of life at 4-6 weeks after radiotherapy, generally followed by improvements in health between six months and a year after treatment. Those who were experiencing late urinary side-effects, one year after radiotherapy had poor urinary function prior to radiotherapy. Some men who reported acute bowel effects at 4-6 weeks after radiotherapy developed late effects. Coping and HRQoL in men receiving prostate cancer treatment were influenced by the individual's life circumstances inclusive of age, spousal support and their perceived HRQoL as well as time (pre and post treatment). Conclusion: Psycho-social interventions in follow-up care need to be developed and these need to be flexible enough to take account of the individual physical and psycho-social needs of men with prostate cancer pre and post-radiotherapy. They are particularly vulnerable in the immediate post-radiotherapy period. Men with little social support may also be most in need of help.
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Duarte, Igor Lemos 1980. "Quimioterapia em dose densa no tratamento adjuvante do câncer de mama localizado = revisão sistemática da literatura com metanálise = Dose dense chemotherapy in the adjuvant treatment of non metastatic breast cancer: a systematic review with meta- analysis." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313864.
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Orientadores: Andre Deeke Sasse, Carmen Silvia Passos LimaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Pacientes com câncer de mama localmente avançado são de alto risco para recidiva após ressecção cirúrgica com intuito curativo. Muitos estudos têm sido realizados na tentativa de se descobrir alguma intervenção adjuvante capaz de reduzir este risco. No entanto, há, na literatura atual, controvérsias no que tange a melhor estratégia terapêutica neste cenário. Discordância entre intensidade de dose e densidade de dose ainda permeiam o tema. O objetivo desta revisão sistemática foi avaliar o exato papel da quimioterapia em dose densa nas pacientes portadoras de câncer de mama local. Foram comparados os efeitos da quimioterapia em dose densa com quimioterapia convencional em pacientes com câncer de mama localizado ou loco-regionalmente avançado. Os desfechos clínicos avaliados foram sobrevida global (SG), sobrevida livre de doença (SLD) e toxicidades severas. A análise dos dados extraídos foi realizada no programa estatístico Review Manager 5.0 (RevMan 5; Cochrane Collaboration Software). As diferentes estratégias de tratamento adjuvante foram avaliadas em conjunto e separadamente. Quatro estudos (3418 pacientes) foram incluídos. A metanálise demonstrou que quimioterapia em dose densa pode melhorar a sobrevida livre de doença (3356 pacientes; HR 0,83; 95% IC 0,73-0,95; p 0,0005), independente do status de expressão hormonal. Não houve benefício em sobrevida global (3356 pacientes, HR 0,86; IC 95% 0,73-1,01; p 0,006), independente do status de receptor hormonal (SG no subgrupo hormônio positivo HR 0,94; 95% IC 0,74-1,21; SG no subgrupo hormônio negativo HR 0,78; IC 95% 0,62-0,99; p 0,28). Regimes em dose densa causaram pequeno aumento em mucosite, porem sem impacto em eventos cardíacos, leucemia ou mielodisplasia. Em conclusão, a quimioterapia adjuvante em dose densa pode melhora sobrevida livre de doença em pacientes com câncer de mama localizado com pouco impacto na segurança. Entretanto não há claro benefício em sobrevida global. Novas pesquisas podem indicar se há algum impacto em sobrevida global, não verificada atualmente em função do tamanho da amostra, e possivelmente qual grupo de pacientes teria maior benefício
Abstract: Patients with locally advanced breast cancer are at high risk for recurrence after surgical resection with curative intent. Many studies have been conducted in an attempt to discover some adjuvant intervention can reduce this risk. However, there is, in the current literature, controversies regarding the best therapeutic strategy in this scenario. Disagreement between dose intensity and dose density still permeate the theme. The aim of this systematic review was to assess the exact role of dose dense chemotherapy in patients with local breast cancer. The effects of dose dense chemotherapy with conventional chemotherapy in patients with localized breast cancer or loco-regionally advanced were compared. The clinical endpoints were overall survival (OS), disease-free survival (DFS) and severe toxicities. The extracted data was performed in Review Manager 5.0 (RevMan 5, Cochrane Collaboration Software) statistical program. The different strategies of adjuvant treatment were evaluated together and separately. Four studies (3418 patients) were included. The meta-analysis showed that dose dense chemotherapy in improvements can free survival (3356 patients, HR 0,83, 95% CI 0,73 to 0,95, p 0,0005), regardless of the status of hormone expression. There was no benefit in overall survival with chemotherapy dose dense (3356 patients, HR 0,86, 95% CI 0,73 ? 1:01, p 0,006), independent of hormone receptor status d (SG subgroup hormone positive HR 0,94, 95% CI 0,74 ? 1:21, SG in the subgroup negative hormone HR 0,78, 95% CI 0,62 ? 0.99, p 0:28). Regimes in dense dose caused small increase in mucositis, however no impact on cardiac events, leukemia or myelodysplasia. DD adjuvant chemotherapy may improve disease-free survival in patients with early breast cancer with little impact on safety. However there is no clear benefit in overall survival. New research may indicate whether there is any impact on overall survival, not currently seen as a function of sample size, and that group of patients will benefit most
Mestrado
Clinica Medica
Mestre em Clinica Medica
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Marta, Gustavo Nader. "Quimioterapia de indução seguida de cirurgia com ou sem radioterapia adjuvante para pacientes com diagnóstico de câncer de cavidade oral: revisão sistemática e metanálise." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-11012016-154920/.
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INTRODUÇÃO: Os tumores da cavidade oral localmente avançados são neoplasias agressivas e com alto risco de recaída após o tratamento radical definitivo. O presente estudo foi realizado para avaliar a eficácia e segurança da quimioterapia de indução antes da cirurgia em pacientes com câncer de cavidade oral. MÉTODOS: Uma revisão sistemática da literatura foi realizada e apenas ensaios clínicos randomizados prospectivos fase III que comparavam a quimioterapia de indução seguida de cirurgia com ou sem radioterapia pósoperatória (Grupo QT) à cirurgia com ou sem radioterapia pós-operatória (Grupo Controle) foram elegíveis. Dois autores selecionaram os estudos de forma independente, respeitando os critérios de elegibilidade preestabelecidos. Avaliou-se também o risco de viés dos estudos incluídos. RESULTADOS: No total, dois estudos foram selecionados. Quatrocentos e cinquenta e um pacientes foram aleatoriamente randomizados para o Grupo QT (n = 226) e para o Grupo Controle (n = 225). A maioria dos pacientes tinha tumores em estádios clínicos III/IV (89,1%). Ambos os estudos foram classificados como tendo baixo risco de viés. Nenhum benefício estatisticamente significante em favor da quimioterapia de indução foi encontrado quanto à recorrência locorregional, à sobrevida livre de doença e à sobrevida global. A análise de subgrupo com dados individuais dos pacientes com doença cervical linfonodal N2 demonstrou benefício estatisticamente significante em sobrevida global no grupo que recebeu quimioterapia de indução. Nenhuma análise estatística foi realizada em relação à segurança das estratégias de tratamento, uma vez que os estudos incluídos não avaliaram diretamente esse desfecho. CONCLUSÕES: Com base nos estudos disponíveis, a quimioterapia de indução não melhora os resultados clínicos em pacientes com câncer de cavidade oral quando administrada antes da cirurgia radical com intenção curativa. O subgrupo de pacientes com doença linfonodal cervical N2 é aquele que eventualmente poderia se beneficiar da estratégia de quimioterapia de induçãoINTRODUCTION: Locoregionally advanced oral cavity cancers are aggressive tumors with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients. METHODS: Only prospective phase III randomized studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS: Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n = 226) versus Control Group (n = 225). Most patients had tumors at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favor of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favor of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes. CONCLUSIONS: Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancers patients. Clinically assessed N2 patients might benefit from induction chemotheraphy
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Johansson, Jeannette. "Antibodies for better or worse or Antibody variability in an egg-laying mammal and a novel strategy in the treatment of allergies." Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2533.
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Antibodies are a central part of the immune defense system, and a large variability in their specificity is needed in order to be able to react against all possible foreign substances we may encounter during our lives. In this thesis, results are presented from investigations into how an egg-laying mammal, the Australian duck-billed platypus (Ornithorhynchus anatinus) creates antibody variability. Our results show that despite the lack of many V gene families the antibody repertoire in the platypus seems to be well developed. A long and highly variable complementarity-determining region (CDR) 3 compensates for the limited germline diversity. Interestingly, the presence of additional cysteine residues in the CDRs may form stabilizing disulfide bridges in the antigen binding loops and thereby increasing the affinity of the antibody-antigen interaction.
Although the immune system is necessary for survival, it must be strictly controlled since it may otherwise over-react and cause more harm than benefits. Allergies and autoimmune diseases are examples of such over-reactions by the immune system. Allergies are increasing in the western world and have become one of the main medical issues of the 21st century. IgE is the central mediator in atopic allergies such as hay fever, eczema and asthma; it is therefore a prime target in the development of allergen-independent preventative treatments. Here we present results from several studies of a novel vaccine strategy aimed at reducing the levels of IgE antibodies. The vaccine results in the induction of anti-IgE antibodies, and the skin reactivity upon allergen challenge was significantly reduced in vaccinated animals. Our results suggest that active immunization against IgE has the potential to become a therapeutic method for humans. In addition, an evaluation of possible adjuvants that could be used as immune stimulators and thus help break self-tolerance at the time of vaccination is presented.
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Cushing, Merta, and Thao Truong. "Efficacy and toxicity of capecitabine/oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) in adjuvant and metastatic treatment of colorectal cancer in patients at the Southern Arizona Veteran Affairs Health Care System." The University of Arizona, 2017. http://hdl.handle.net/10150/624166.
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Class of 2017 AbstractObjectives: To determine the efficacy and toxicity of fluorouracil/leucovorin/oxaliplatin (FOLFOX) versus capecitabine/oxaliplatin (XELOX) in the treatment of colorectal cancer (CRC) in the adjuvant (aCRC) and metastatic (mCRC) setting in Veterans at the Southern Arizona Veteran Affairs Health Care System (SAVAHCS). Methods: A retrospective chart review was conducted to collect efficacy and toxicity data. Subjects were included based on age, treatment setting and regimen in the preset 5-year period, and appropriate diagnosis via International Classification of Diseases-Revision 9 (ICD-9) codes. Efficacy was measured via 1-year disease-free survival (DFS) for aCRC, progression-free survival (PFS) for mCRC, and overall survival (OS) for both settings. Results: A total of 79 subjects were initially enrolled with 51 and 54 all-male subjects included in the efficacy and toxicity analysis, respectively. Mean range of age was 63-72 years old. Subjects were divided into four groups: FOLFOX aCRC (17) and mCRC (19), XELOX aCRC (10) and mCRC (8). No difference was found in 1-year DFS and OS between aCRC groups, and PFS between mCRC groups; a higher incidence of 1-year OS with FOLFOX in the mCRC setting was noted (p = 0.03). No difference was found in toxicity between FOLFOX and XELOX, except a higher incidence of hand-foot syndrome in XELOX (p = 0.0007). Conclusions: Efficacy between FOLFOX and XELOX in aCRC and mCRC is similar, while toxicity is slightly more prevalent in XELOX due to increased hand-foot syndrome incidence. These findings agreed with the results reported by prospective clinical trials.
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Rahmani, Samir. "The pathophysiological effects of adjuvant preoperative chemotherapy and/or radiotherapy on patients with advanced rectal cancer : 'neoadjuvant treatment is a two edged sword in patients with advanced colorectal cancer'." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/5001/.
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Introduction The modern treatment of colorectal cancer consists of surgery, with or without adjuvant pre-operative radiotherapy, chemotherapy or chemoradiotherapy (APT) for selected cases. In the United Kingdom, therapy may be given prior to surgery in an attempt to facilitate surgical excision and improve survival. However, there is some evidence that APT in other cancers may adversely affect the patient’s health and increase the risk of operative morbidity. The association between functional capacity, represented by the maximum oxygen consumption per unit time (VO2max) as measured by cardiopulmonary exercise testing (CPEX), and the perioperative outcome is well established. A reduction in cardiopulmonary reserve may increase the perioperative mortality and morbidity; however, sufficient data to demonstrate this are not available yet. This study examined the affect of APT on the cardiopulmonary status, body composition, cytokines assay, nutritional status and quality of life in patients with colorectal cancer. Methods This is a pilot observational study performed on two groups of patients, no intervention was used at this stage. Group one received combined ChemoRadiotherapy and Group two received only pelvic radiotherapy. Cardiopulmonary function was measured with exercise bicycle to achieve Anaerobic Threshold (AT) and Maximum Oxygen consumption (VO2max) using CPEX testing. Anthropometric parameters such as mid-arm circumference (MAC), Triceps skin fold (TSF), grip strength measurements (GS), Body weight, height and body mass index as well as extracellular water (ECW), intracellular water (ICW), total body water (TBW) and fat free mass (FFM) were measured using a Bio-electrical impedance analyser. 9 cytokines were measured using a Luminex assay in addition to CRP and albumin assessment. Nutritional status and quality of life were evaluated using two validated questionnaires (EORTC QLQ-C30 and PG-SGA). These assessments were made before and within two weeks after the administration of APT. Wilcoxon rank sum test represented in median and interquartile range was used to compare results before and after the exposure to APT. Results Between January 2010 and January 2011, a total of 36 patients with rectal cancer were recruited, 24 patients in group 1 had combined chemoradiotherapy (mean age 59.4, 18 males and 6 females) and 12 patient in group 2 had radiotherapy only (mean age 71.8, 10 males and 2 females). Group 1 had a significant decline in VO2max with p=0.005, an increase in the ventilatory equivalent ratio for CO2 (VE/VCO2) with p= 0.001, a reduction in TSF, MAC, GS and TBW with p- values of 0.007, 0.006, 0.010 and 0.000 respectively after APT exposure. Group 2 had no significant changes in their CPEX data, however, they showed a marked decline in TSF, MAC, GS, TBW and FFM with p- values of 0.013, 0.013, 0.002 and 0.034 respectively after APT exposure. Both groups showed a highly significant overall reduction in the health related quality of life data with no significant changes in their plasma cytokines, CRP and albumin post APT. Conclusions These data suggest that APT has a significant effect upon the cardiopulmonary capacity with reduced VO2max as well as an increased VE/VCO2. There were also signs of fluid depletion and reduced muscle bulk represented by a significant reduction in TBW, FFM, MAC and TSF. Therefore, these important physiological changes could be deleterious and affect the peri and post-operative recovery and increase the morbidity of surgery in colorectal cancer patients. In view of this, a period of optimisation following APT and prior to surgery may serve to minimise the risk of such complications.
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Chang, Kai Yuan. "Tyrosine hydroxylase inhibition : and L-ascorbic acid 2-phosphate uptake by chromaffin cells and influenece of treatment of cyclosporine a and cyclosporine G on lymphoctye responsiveness and adjuvant arthritis in rats." Thesis, Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/27583.
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