Dissertations / Theses on the topic 'Cancer – Adjuvant treatment'
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1
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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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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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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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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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.
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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
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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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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.
10
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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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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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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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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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.
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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
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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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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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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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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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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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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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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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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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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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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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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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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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Chen, Guofang [Verfasser]. "Effect of metformin on growth of differentiated thyroid cells and thyroid carcinoma cells and their derived cancer stem cells : implication for metformin as adjuvant treatment for undifferentiated thyroid cancer / Guofang Chen." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2012. http://d-nb.info/1029792062/34.
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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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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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Chan, Wing-keung, and 陳永強. "The immunomodulatory effects of purified {221}-glucans and {221}-glucan containing herbs." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557996.
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Wells, Thomas Peter Edward. "Optimising the therapeutic ratio of adjuvant breast cancer treatments : assessment of chemoradiation heart damage with serum cardiac troponin I and the use of open MRI in adjuvant breast radiotherapy planning." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424051.
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Zhang, Zhu. "Exploration of the anticancer mechanisms of novel chemotherapeutic adjuvants involving autophagy and immune system reprogramming in the treatment of pancreatic cancer." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/755.
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Pancreatic cancer is known to be one of the most life-threatening cancers characterized by aggressive local invasion and distant metastasis. The high basal level of autophagy in pancreatic cancer may be responsible for the low chemotherapeutic drug response rate and poor disease prognosis. However, the clinical application of autophagy inhibitors was unsatisfactory due to their toxicity and minimal single-agent anticancer efficacy. Hence, oncologists begin to consider the tumor microenvironment when exploring new drug targets. In the present study, the anti-tumorigenic mechanisms of two major phytochemicals derived from Chinese medicinal herbs had been investigated against pancreatic cancer development. Calycosin is a bioactive isoflavonoid of the medicinal plant Astragalus membranaceus. Our results have shown that calycosin inhibited the growth of various pancreatic cancer cells both in vitro and in vivo by inducing cell cycle arrest and apoptosis. Alternatively, calycosin also facilitated MIA PaCa-2 pancreatic cancer cell migration in vitro and increased the expression of epithelial-mesenchymal transition (EMT) biomarkers in vivo. Further mechanistic study suggests that induction of the Raf/MEK/ERK pathway and facilitated polarization of M2 tumor-associated macrophage in the tumor microenvironment both contribute to the pro-metastatic potential of calycosin in pancreatic cancer. These events appear to be associated with calycosin-evoked activation of TGF-β signaling, which may explain the paradoxical drug actions due to the dual roles of TGF-β as both tumor suppressor and tumor promoter in pancreatic cancer development under different conditions. Isoliquiritigenin (ISL) is a chalcone obtained from the medicinal plant Glycyrrhiza glabra, which can be a precursor for chemical conversion to form calycosin. Results have shown that ISL decreased the growth and EMT of pancreatic cancer cells in vitro, probably due to modulation of autophagy. ISL-induced inhibition of autophagy subsequently promoted reactive oxygen species (ROS) production, leading to induction of apoptosis in pancreatic cancer cells. Such phenomenon also contributed to the synergistic growth-inhibitory effect in combined treatment with the orthodox chemotherapeutic drug 5-fluorouracil. In addition, ISL-induced tumor growth inhibition in vivo was further demonstrated in a tumor xenograft mice model of pancreatic cancer. ISL promoted apoptosis and inhibited autophagy in the tumor tissues. Study on immune cells indicates that ISL could reduce the number of myeloid-derived suppressor cells (MDSCs) both in tumor tissue and in peripheral blood, while CD4+ and CD8+ T cells were increased correspondingly. In vitro test has revealed that ISL inhibited the polarization of M2 macrophage along with its inhibition of autophagy in M2 macrophage. These immunomodulating effects of ISL had reversed the pro-invasive role of M2 macrophage in pancreatic cancer.In conclusion, calycosin acts as a "double-edged sword" on the growth and metastasis of pancreatic cancer, which may be related to the dual roles of TGF-β and its influence on the tumor microenvironment. Alternatively, ISL consistently inhibited the growth and metastatic drive of pancreatic cancer through regulation of autophagy and reprogramming of the immune system. The differential modes of action of these compounds have provided new insights in the development of effective pancreatic cancer treatment adjuvants.
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Edery, Livia. "Analyse psychodynamique de la relation médecin-malade lors de la prise de décision thérapeutique chez des patientes atteintes d'un cancer du sein : refus ou acceptation de la chimiothérapie adjuvante ?" Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAG042.
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Objectifs: Cette thèse étudie les aspects conscients et inconscients de la prise de décision thérapeutique, proposée par l’oncologue lors d’un entretien, par des patientes atteintes d’un cancer du sein. Ces patientes ont toutes subi une chirurgie curative de leur cancer et peuvent toutes bénéficier potentiellement d’une chimiothérapie adjuvante. La décision pourra être positive ou négative aux yeux du médecin, mais sa perception ne correspond pas à l’issue finale du processus psychique toujours en cours d’élaboration chez la patiente. Contrairement à la littérature internationale nous avons choisi de ne pas nous focaliser sur les éléments manifestes du choix thérapeutique mais d’explorer aussi les possibilités d’adaptation et de défenses inconscientes, lors de l’annonce du traitement des patientes, en fonction de leur personnalité. Cette approche clinique holistique montre que 4 grands co-facteurs interviennent dans la prise de décision de la patiente. Matériel et Méthodes : Cette étude clinique longitudinale compare les facteurs psychologiques dans la prise de décision, en consultation avec l’oncologue, de 50 patientes suivies pour un cancer du sein. Résultats : 82 % des patientes ont accepté la chimiothérapie adjuvante et 18 % l'ont refusée. Le groupe Adhésion manifeste surtout une réaction dépressive alors que chez le groupe Refus, prédominent les traits de personnalité hostiles. L’anxiété, significativement plus élevée dans le groupe Adhésion que dans le groupe Refus, semble liée à la répression des émotions des malades qui se soumettent à la proposition médicale. Les patientes qui refusent le traitement expriment, au contraire, verbalement leurs émotions hostiles à l’égard des médecins et de la Médecine. Conclusion : L’adaptation des modes de communication du médecin, et la connaissance plus approfondie des traits de personnalité des patients pourraient faciliter le niveau de participation des patients à leur protocole thérapeutiquePurposes : This thesis studies the conscious and unconscious aspects of the therapeutic decision-making, suggested by oncologist during consultation, by patients affected by breast cancer. All patients had a curative surgery of their cancer and they can benefit from adjuvant chemotherapy. In the eyes of physician the decision can be positive or negative but its perception does not correspond to ultimate’s outcome of the psychic process, in progress, of patient elaboration.The international literature focus on obvious elements of patients’ therapeutic choice during therapeutic disclosure. In addition, our study investigates the possibilities of adaptation and unconscious defenses according to their personality. This holistic clinical approach shows that 4 mains co-factors involve in patient’s decision-making. Population and methods : This is a comparative and longitudinal clinical research of the medical consultation with 50 patients. Patients psychological factors of the decision-making has been registered and analysed. Results : 82% of patients have accepted adjuvant chemotherapy while 18% refused it. The Adhesion group had mainly a depressive reaction while the Refusal group had predominant hostile personality traits. The anxiety was significantly higher in the Adhesion group than in the Refusal. Adhesive patients seemed to repress their emotions when accepting the treatment while Refusal group expressed emotions in words. Conclusion : Adaptation of the physicians communication and investigation of patients personality should enhance the decision-making of patients when they must decide or not of treatment continuation despite secondary effects
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Lavriv, Daryna Sergiyivna. "Should omega-3 fatty acids be used for adjuvant treatment of cancer cachexia?" Master's thesis, 2017. http://hdl.handle.net/10451/31267.
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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017Objectives: Cancer cachexia is characterised by a progressive loss of muscle, resulting in functional impairment and shorter survival. Therefore, omega-3 has been studied for its role as an anti-cachectic therapy. This systematic review identified studies published on use of omega-3 in cancer cachexia in order to examines the potential benefit. Methods: A systematic literature search of the PubMed database and B-on database was conducted in March 2015 to identify studies published between 2000 and 2015. Of 140 publications, 7 were selected on the basis of their methodological quality, according to the Delphi List. The collected data was summarized and written in text format and in tables. Results: Only one study, made in precachectic population, show statistically and clinically positive intervention. No benefits were observed with the 4g EPA/day, but a potentially clinically relevant treatment effect with 2g EPA/day. Lung tumors showed the highest CRP levels and while the weight of patients with gastrointestinal cancer increased significantly, patients with lung cancer showed no significant response. Conclusions: Future cachexia trials would likely benefit from studying a single tumor type with earlier stage disease, with probably different dosage depending on the type and inflammation profile.
Objetivos: A caquexia do cancro caracteriza-se por uma progressiva perda de massa muscular, que resulta num prejuízo funcional e numa diminuição da sobrevida. Tendo isso em conta, tem sido estudado o papel do ómega-3 na terapêutica da caquexia. Esta revisão sistemática identificou os estudos publicados acerca do uso do ómega-3 na caquexia do cancro por forma a identificar o potencial beneficio. Métodos: Uma pesquisa sistemática da literatura na base de dados PubMed e B-on foi realizada em Março de 2015, por forma a identificar estudos publicados entre 2000 e 2015. Das 140 publicações, 7 foram selecionadas com base na sua qualidade metodológica, de acordo com a Lista de Delphi. A informação obtida foi resumida e escrita em formato de texto e tabelas. Resultados: Apenas um estudo, realizado numa população pré-caquética, revelou a intervenção como sendo estatisticamente e clinicamente positiva. Não foram observados benefícios com 4g de EPA/dia, mas um potencial efeito clinicamente relevante foi observado com 2g de EPA/dia. O cancro do pulmão demonstrou os níveis de PCR mais elevados e enquanto que o peso dos doentes com cancro gastrointestinal aumentou significativamente, os doentes com cancro do pulmão não demonstraram uma resposta significativa. Conclusões: Futuros ensaios acerca da caquexia poderiam provavelmente beneficiar em estudar um único tipo de tumor, em estádios mais precoces, e com dosagens diferentes conforme o tipo de tumor e o seu perfil inflamatório.
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Ferreira, Arlindo. "Adjuvant endocrine therapy for the treatment of early breast cancer : real world effectiveness, tolerability and adherence." Doctoral thesis, 2020. http://hdl.handle.net/10451/48473.
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O tratamento hormonal adjuvante de doentes com carcinoma da mama melhora a sobrevivência global. O uso em contexto de mundo real, efetividade, tolerabilidade e adesão a inovações recentes da terapia hormonal adjuvante de cancro da mama não está bem caracterizado. Para abordar estes pontos e assim apoiar a tomada de decisão de doentes-médicos e a investigação clínica futura desenvolvemos uma série de projetos com o propósito de: 1) descrever a implementação na prática clínica de mundo real de inovações recentes no campo da terapia hormonal adjuvante de cancro da mama e sumarizar a sua efetividade, 2) quantificar o impacto da terapia hormonal adjuvante na qualidade de vida das doentes e 3) quantificar a adesão e persistência das doentes à terapia hormonal adjuvante. Para concluir estas tarefas utilizámos diferentes estudos de coorte e aplicámos métodos padrão e inovadores de análise de dados.
Fazendo recurso de duas coortes retrospetivas derivadas do Registo Oncológico Regional do Sul, a primeira com ~1300 mulheres pós-menopáusicas e a segunda com ~1700 mulheres pré-menopáusicas, identificámos que quer os inibidores da aromatase (IA) quer a supressão da função ovárica (SFO) foram introduzidos com sucesso na prática clínica após publicações científicas de referência em 2005 e 2014, respetivamente. Na coorte pós-menopáusica, 41% das doentes receberam um IA (16% em monoterapia e 25% em sequência) e 59% tamoxifeno com diferenças por centro. Após um acompanhamento mediano de 6.3 anos, os IA associaram-se a melhor sobrevivência global (SG) quando comparados com tamoxifeno (HR-ajustado 0.5, IC 95% 0.37-0.81). Fazendo recurso complementar de uma coorte retrospetiva estado-unidense de ~800 mulheres pós-menopáusicas com tumores lobulares, registámos resultados semelhantes e não foi identificada heterogeneidade de eficácia por tipo histológico, em específico quando comparando carcinomas lobulares puros a carcinomas ductais e lobulares mistos. Na coorte pré-menopáusica, 17% das doentes foram tratadas com SFO com um crescimento substancial do uso de 2014 em diante (16% vs. 25% após 2014), particularmente para a combinação com IA (0.4% vs. 8% após 2014). Após um acompanhamento mediano de ~3 anos, doentes tratadas com SFO tiveram melhor SG que doentes não tratadas com SFO (HR-ajustado 0.44, IC 95% 0.19-0.96). Fazendo recurso de uma sub-coorte de ~4300 doentes com cancro da mama com resultados reportados por doente (patient reported outcomes) disponíveis do estudo CANTO, uma coorte prospetiva francesa, descrevemos um impacto substancial do tratamento na qualidade de vida (QdV) 2 anos após o diagnóstico. Usando o C30 summary score da EORTC, um resultado compósito de várias funções e sintomas, a terapia hormonal, mas não a quimioterapia, teve um impacto persistente na QdV 2 anos após o diagnóstico com diferenças nos domínios impactados. Adicionalmente, expusemos um efeito diferencial do tratamento por estado menopausico: em doentes pré-menopáusicas a quimioterapia parece ser o promotor principal da deterioração de domínios de QdV, enquanto que em doentes pós-menopáusicas foi a terapia hormonal o promotor principal da deterioração da QdV. Finalmente, fazendo recurso de uma segunda sub-coorte de ~1200 derivada do estudo CANTO e de doentes que estavam a tomar tamoxifeno e com avaliação sérica do tamoxifeno, identificámos que 1 em cada 6 mulheres (16%) eram não-aderentes ao tratamento, i.e. tinham os valores séricos de tamoxifeno abaixo da linha de corte de adesão. Esta proporção foi maior que aquela auto-reportada (12.3%). Após um acompanhamento mediano de 2 anos após a avaliação do tamoxifeno sérico, doentes não aderentes quando avaliadas por via bioquímica tiveram uma sobrevivência livre de recidiva à distância mais curta (HR-ajustado de 2.31, IC 95% 1.05-5.06).
Este trabalho detalhou a cinética de introdução na prática clínica de inovações recentes na terapia hormonal adjuvante. Adicionalmente, revelou evidência de mundo real da efetividade de IA e SFO adjuvantes. Estes dados sugeriram porém que para uma proporção substancial de doentes a terapia hormonal leva a um impacto persistente e negativo na QdV, especialmente em mulheres pós-menopáusicas, tal como a uma proporção alarmante de não-adesão ao tratamento, até certo ponto relacionada com questões de tolerabilidade.Adjuvant endocrine therapy leads to substantial gains in breast cancer survival outcomes. The real-world use, effectiveness, tolerability and adherence to recent innovations in the field of adjuvant endocrine therapy for breast cancer is not well characterized. To tackle these concerns and hence help patient-physician decision making and future clinical research we developed a series of projects aiming to: 1) describe the implementation in real-world practice of recent innovations in the field of adjuvant endocrine therapy for breast cancer and summarize its effectiveness, 2) quantify adjuvant endocrine therapy impact on patients’ quality of life and 3) quantify patients adherence and persistence to adjuvant endocrine therapy. To do this, we used different cohort studies and applied standard and novel statistical methods. Using two retrospective cohorts from Southern Portugal Cancer Registry, one of ~1300 postmenopausal women and the other of ~1700 premenopausal women, we identified that both aromatase inhibitors (AI) and ovarian function suppression (OFS) were successfully introduced in clinical practice after landmark publication in 2005 and 2014, respectively. In the postmenopausal cohort, 41% of patients received an AI (16% as monotherapy, 25% as sequential therapy) and 59% tamoxifen with differences by center. After a median follow-up of 6.3 years, AI use was associated with a better overall survival (OS) when compared with tamoxifen (adjusted-HR 0.55, 95% CI 0.37-0.81). Using a complementary retrospective US cohort of ~800 postmenopausal women with lobular tumors, similar findings were registered and no heterogeneity in efficacy was recorded by histology, in specific comparing pure lobular carcinomas to mixed ductal and lobular carcinomas. In the premenopausal cohort, 17% of patients were treated with OFS with a substantial increase of its use from 2014 onward (16% vs. 25% after 2014), particularly for the combination with AI (0.4% vs. 8% after 2014). After a median follow-up of ~3 years, patients treated with OFS had a better OS than those not treated with OFS (adjusted-HR 0.44, 95% CI 0.19-0.96). Using a sub-cohort of ~4300 breast cancer patients with available patient reported outcomes from CANTO, a nationwide French prospective cohort, we described a substantial impact of treatment on QoL 2 years after diagnosis. Using the EORTC C30 summary score, a composite score of several functions and symptoms, endocrine therapy but not chemotherapy had a persistent impact on QoL 2 years after diagnosis with differences by specific domains. In addition, we uncovered a differential effect of treatment by menopausal status: in premenopausal patients CT seems to be the predominant driver of QoL domains deterioration, whereas in postmenopausal patients it was ET the predominant driver of QoL deterioration. Finally, using a second sub-cohort of ~1200 patients from CANTO that were taking adjuvant tamoxifen and with serum assessment of tamoxifen, we identified that 1 in every 6 women (16%) were non-adherent, i.e. had serum tamoxifen levels were below the adherence threshold. This proportion was higher than the self-reported rate of non-adherence (12.3%). After a median follow-up time of 2 years from tamoxifen serum assessment, biochemically defined non-adherent patients had a shorter DDFS (adjusted-HR of 2.31, 95% CI 1.05-5.06). This work detailed the kinetics of introduction in clinical practice of recent adjuvant endocrine treatment innovations. In addition, it provides real-world evidence of the effectiveness of adjuvant AIs and OFS. Nevertheless, it suggests that for a substantial number of patients endocrine therapy leads to a persistent negative impact on QoL, especially in postmenopausal women, and to an alarming proportion of non-adherence to treatment, to a certain extent related to tolerability issues.
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Asigbee, Priscilla A. "Verifying monitor unit calculations for tangential whole-breast fields in three-dimensional planning." 2014. http://liblink.bsu.edu/uhtbin/catkey/1745599.
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Söderström, Karin. "Radiotherapy for head and neck cancer : costs and benefits of time, dose and volume." Doctoral thesis, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-131021.
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Background In the treatment of head and neck cancers (HNCs), radiotherapy (RT) has the advantage of organ preservation compared to surgery. However, treatment toxicities associated with RT can affect important functions for everyday life, both in the acute and late stage. RT to macroscopic tumour in HNC is commonly combined with elective RT to cervical lymph nodes at risk of microscopic involvement. The resulting risk reduction of the elective treatment based on dose-volume parameters is sparsely evaluated. So is the relationship between the elective treatment and treatment toxicity. The present thesis addresses these aspects. A strategy aimed at improving the outcome of RT is accelerated fractionation (AF). AF strives to shorten total treatment time to minimise proliferation of the tumour tissue during the RT period. We have investigated the impact of AF on both disease control and toxicity. Methods In the ARTSCAN study, 750 patients with localised HNC were randomised between AF (68 Gy in 4.5 weeks) and conventional fractionation (CF) (68 Gy in 7 weeks). The elective treatment volume was prescribed 46 Gy with CF in both treatment arms. The thesis is based on four individual papers, investigating the issues above in the whole study population or in sub-populations. Results No difference in disease control or late toxicity between CF and AF was observed at five years. However, there was an increased acute toxicity with AF. Weight loss was associated with treatment volume, independent of tumour stage. The elective treatment volume was found to be an independent risk factor for late aspiration, as well as mean dose to the pharyngeal constrictor muscles, neck dissection, and age at randomisation. There was a significant risk reduction for node relapses in volumes treated to an elective dose. Only a relapse in volumes treated to >60 Gy affected the survival. Conclusion The present thesis questions the benefit of AF in definitive RT as well as extensive elective treatment of the cervical nodes.
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Hinkle, David T. "CORRELATING IRINOTECAN AND CAPECITABINE TREATMENT FOR COLORECTAL CANCER TO GENE EXPRESSION, POLYMORPHISMS, AND CLINICAL OUTCOMES." Thesis, 2011. http://hdl.handle.net/1805/2510.
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Indiana University-Purdue University Indianapolis (IUPUI)Colorectal cancer is the third most common type of cancer and the third most common cause of cancer-related mortality. There are three types of treatment available to patients, either individually or in combination. Treatments are radiation, chemotherapy, and surgery. In a Phase II clinical trial at IUSM, a multimodality approach was chosen. The patients with locally advanced rectal cancer received preoperative treatment with capecitabine and irinotecan (CPT-11) combination followed by chemoradiation with capecitabine and finally surgery to improve response and decrease local recurrence. Irinotecan and Capecitabine are both prodrugs activated in vivo to SN-38 and 5-FU, respectively. Identification of the molecular markers for 5-FU and Irinotecan efficacy and toxicity is important for the development of more efficient and less toxic treatment strategies for patients with colorectal cancer. The goal of this study was to determine the expression levels of the genes involved in activation and metabolism of capecitabine and irinotecan in pre and post treatment specimens from these patients. The genes quantitated by real-time PCR were carboxylesterase 1 and 2 (CES1 and CES2), thymidylate synthase (TS), β-glucoronidase (β-GUS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and topoisomerase I (Topo I). The UGT1A1*28 polymorphism in UDP glucuronosyltransferase 1 is associated with SN-38 toxicity. Therefore, the UGT1A1*28 polymorphism status in patients was determined by PCR-sequencing. Correlative analysis of gene expression and UGT1A1*28 mutation with clinical outcome in this Phase II study was completed.
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Lima, Isac da S. F. "Effects of Timing of Adjuvant Treatment on Survival of Patients with Stage III Colon Cancer and Stage II/III Rectal Cancer in Alberta." Master's thesis, 2010. http://hdl.handle.net/10048/1341.
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Surgery followed by adjuvant treatment has been an evidence-based treatment recommendation for stage III colon cancer and stage II/III rectal cancer since 1990. Clinical trial results are, however, uninformative regarding the definitive outer limit by which adjuvant treatment should be received for optimal survival benefit. The purpose of my thesis research was to assess the effect that the timing of adjuvant therapy has on patient survival in actual clinical practiceEpidemiology
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Nascimento-Fonseca, Sandra Marques. "Outcomes of patients with stage IB1 and IB2 Cervical Cancer who have had Wertheim's Hysterectomies with or without adjuvant chemo-radiotherapy as primary treatment at Charlotte Maxeke Johannesburg Academic Hospital." Thesis, 2018. https://hdl.handle.net/10539/25267.
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A research report submitted to the University of the Witwatersrand in partial fulfilment for the degree of Master of Medicine
2016.Background Cervical cancer is the 3rd most common female malignancy worldwide. It is classified and managed according to stage as defined by the FIGO Committee on Gynaecology Oncology classification of 2009. Stage specific treatment is tailored according to prognosis and risk of recurrence as determined by tumour type, tumour size, tumour grade, lymph node metastases, lymphovascular space involvement (LVSI), parametrial spread and presence of any other metastatic deposits at presentation. This study only concentrated on patients who presented with Stage IB1 and 1B2 tumours managed by Class III / Meig’s Radical / Wertheim’s hysterectomy and bilateral pelvic lymphadenectomy. Aims Primary Outcome 1. Assess disease free interval and overall survival 2 years post-operatively. Secondary Outcomes 1. Assess adequacy of patient selection 2. Assess risk factors for recurrence 3. Compare recurrence risk of HIV positive patients versus HIV negative patients. 4. Determine surgical and post-surgical complication rate. Materials and Methods This was a retrospective institutional cohort study conducted at the Charlotte Maxeke Johannesburg Academic Hospital. All patients with Stage IB1 or IB2 cervical cancer treated with Wertheim hysterectomies between 2002 and 2012 were included. Surgical records, histology records, further postoperative management records and gynaecological outpatient follow up records were used to collect data for the patients. Histological findings post-operatively determined further management. Surgical margins had to be 10mm clear of tumour with no positive lymph nodes otherwise external beam radiotherapy and brachytherapy or chemo-radiotherapy were recommended in addition to primary surgical management. Results Of the 72 patients initially identified, 69 patients were suitable for study inclusion. The mean age of the study population was 45 years. Study population racial distribution: 68.12% were Black, 26.09% were White, 2.9% were Coloured and 2.9% were Indian. Average parity and gravidity of patients alive at the end of the study was 2.86 and 3.56; while average parity and gravidity of patients deceased at the end of the study was 2.5 and 2.8 respectively. Study population ECOG status: 16% were ECOG 0, 83% were ECOG 1 and 1% were ECOG 2. Overall survival at the end of the study was 86% and patients were disease free postoperatively for an average of 5 years. Thirty three percent of the patients were disease free for more than 5 years. Preoperative clinical staging and postoperative histological staging correlated only in 61% of cases. Correct management by Wertheim’s hysterectomy was rendered to 75% of patients whereas the remainder were incorrectly managed and should have had either a simple hysterectomy with no pelvic lymphadenectomy or radiotherapy only as primary therapy. More advanced stages, tumours ≥ 4cm, adenomatous cell type, > 5mm depth of invasion, >7mm lateral spread, higher number of nodes positive for metastatic disease, surgical margins 10mm, positive lympohovascular space, parametrial and pouch of Douglas (POD) involvement were factors that had a poorer prognosis with regards overall survival, disease-free interval or both. Poorly differentiated tumours were more likely to recur but did not have a poorer prognosis compared with regards to overall survival or disease free interval at 2 or more years compared to well and moderately differentiated tumours. Mortality of HIV reactive patients was 16.7% compared to 12.5% for HIV non-reactive patients. This difference was not statistically significant at the 95% confidence level. HIV status also did not increase risk of recurrence. Lower CD4 counts were shown to have a lower disease-free period and overall survival. Intra-operative surgical complication rate was 6%. Immediate post-operative complication rate was 16%. Of the patients who required DXT or DXT and chemotherapy 33% had side-effects or complications from adjuvant therapy. Patients treated with DXT and chemotherapy had had more side-effects than those treated with DXT only. Conclusion The mean age of the study population was 45 years. This was lower compared to other larger studies possibly due to younger presentation related to HIV disease. HIV positive patients with lower CD4 counts were shown to have poorer prognosis with regards to survival. HIV status was not shown to be a risk factor for recurrence. The overall survival and disease-free period at 5 years was similar to that of other international studies. Only two thirds of the patients were adequately selected for surgery according to the institution’s criteria for a Wertheim’s hysterectomy and therefore it may be necessary to reconsider the pre-operative assessment of these patients. More advanced stages, tumours ≥ 4cm, adenomatous cell type, poor differentiation, > 5mm depth of invasion, >7mm lateral spread, higher number of nodes positive for metastatic disease, surgical margins ≤ 10mm, positive lympohovascular space, parametrial and pouch of Douglas involvement were factors that had a poorer prognosis with regards to recurrence, overall survival and disease-free interval. However, the rates of recurrence were not statistically significant at a 95% confidence level.
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Chang, Ching Ching, and 張菁菁. "Hot flashes and sleep disturbance among women after breast cancer surgery: Comparison between different adjuvant treatments." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/41572070743868722358.
Full textAbstract:
碩士長庚大學
護理學研究所
96
Hot flashes is a common but ignored symptom during the period of treatments in women with breast cancer. It has impact on physiological or psychological status. The purpose of the study was to understand the prevalence of hot flashes and its relationship with sleep disturbance among women with breast cancer from pre-surgery to one year after surgery. In order to discuss the effect of different treatments on relationship of hot flashes and sleep disturbance, patients were divided into two groups: receive chemotherapy alone and chemotherapy combined hormonal therapy. Patients were assessed at baseline (pre-operation), mid-chemotherapy, end-chemotherapy and 1 year post-operation. Data were analyzed with descriptive statistics, Chi-Squared test and Hierarchical Linear Model (HLM). A total of 142 patients were selected from a large study. Prevalence of hot flashes in two groups were highest at post-operation and lowest at mid-chemotherapy; however no significant difference was found between two groups. The severity and distress of hot flashes in two groups were also not different. The sleep disturbance of patients in two groups were both highest at mid-chemotherapy and lowest at post-operation. Sleep disturbance were decrease significantly over time, moreover presence of hot flashes was associated with higher sleep disturbance. Treatment type did not influence the effect of sleep disturbance over the time. After adjusted for age, treatment, pain, depression, fatigue, performance and the severity of menopausal symptoms, patients who got hot flashes frequently were more likely to have decreased sleep quality over time.
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Le, Renard Pol-Edern. "Injectable formulations forming an implant in situ as vehicle of silica microparticles embedding superparamagnetic iron oxide nanoparticles for the local, magnetically mediated hyperthermia treatment of solid tumors." Phd thesis, 2011. http://tel.archives-ouvertes.fr/tel-00709676.
Full textAbstract:
Cette thèse présente les travaux de développement de formulations injectables capables de se solidifier in situ, formant ainsi un implant piégeant des microparticules magnétiques en vue du traitement de tumeurs par induction magnétique d'une hyperthermie locale modérée. Nous exposons tout d'abord le contexte physique, biologique et clinique de l'hyperthermie comme traitement anticancéreux, particulièrement des modalités électromagnétiques. Les performances in vitro et in vivo des matériaux et formulations sont alors présentées. L'objet du chapitre suivant est la caractérisation des propriétés physicochimiques, magnétiques, et chauffantes, dans un champ magnétique alternatif (115 kHz, 9 - 12 mT), des microparticules de silice renfermant des nanoparticules d'oxyde de fer superparamagnétiques (SPIONs) et de deux de leurs formulations: un hydrogel d'alginate de sodium et un organogel de poly(éthylène-co-alcool vinylique) dans le diméthylsulfoxide. Finalement, nous présentons le potentiel thérapeutique de 20 minutes d'hyperthermie locale induite après injection de l'organogel superparamagnétique dans un modèle murin sous-cutané de tumeurs nécrosantes de colocarcinome humain.