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1
VERDERIO, MARIA. "Terapia adiuvante nell'adenocarcinoma dell'endometrio ad alto rischio." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/44123.
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Introduction
Endometrial cancer is the most common gynecological cancer in developed countries and is diagnosed in 75-80% of cases at FIGO stage I with a 5 years survival rate of 80-90%.
Furthermore, patients with high grade tumors, deep myometrial invasion or advanced stage disease have a poor prognosis and receive adjuvant therapy after surgery. It is not clear whether radiotherapy (RT), chemotherapy (CT) or radiochemotherapy (RT/CT) is better.
Materials and Methods
We reviewed all high risk endometrial cancer cases (Stage IB G3; IC G2-3; IIA G3 or IIA G2 with myometrial invasion > 50%; IIB; IIIA-B-C) with no residual tumors after surgery referred to S.Gerardo Hospital from Genuary 1988 to December 2011. We divided them into four groups based on the different adjuvant therapy used (RT, CT, RT/CT, none) and we have recorded, for each group, relapses and deaths. The aim of the study is to establish the best adjuvant therapy in term of overall survival and progression free survival.
Results
357 patients were eligible for the study; 141 (39,5%) have received no adjuvant therapy, 114 (53,2%) RT; 62 (28,7%) CT; 40 (18%) RT/CT. Relapses were 29 (20%), 31 (27%), 22 (35%), 6 (15%) respectively with p=0.66. Median progression free survival was similar for observation arm and CT-RT arm, while RT alone and CT alone did significantly worse; overall survival was significantly better in the CT-RT arm.
Conclusion
The arm radiochemotherapy has a better progression-free survival and a better overall-survival, despite the fact that the patients with the most severe risk factors for relapse were preferably treated with the combined therapy. The poor performance of chemotherapy deserves further analysis.
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Petryk, Alicia Ailie. "Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy." Thesis, Dartmouth College, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3634608.
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Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.
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Hill, Deirdre A. "Hormone use patterns, intrauterine device use, and endometrial cancer /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/10899.
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Moe, Maung. "Biomarkers to individualise adjuvant systemic therapy in early breast cancer patients." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/50864/.
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Background Adjuvant chemotherapy, endocrine therapy, anti-HER2 therapy and radiotherapy significantly improve recurrence free and overall survivals in early breast cancers. Indications for a particular therapy have been well defined. Examples include oestrogen receptor positivity for endocrine therapy; HER2/Neu protein overexpression for anti-HER2 therapy; young age group, lymph node positivity, nuclear grade 3 and triple negativity (ie, ER/PR/HER2 negative) etc for chemotherapy; lumpectomy, > 5 cm tumour size, > 4 lymph nodes involvement etc for radiotherapy. Compared to no chemotherapy adjuvant chemotherapy can reduce the 10 years breast cancer mortality risk by one third although the absolute benefit depends on the absolute risk before the adjuvant chemotherapy as the risk reduction is proportional. The absolute risk depends on the various clinical and histopathological risk factors such as age, nuclear grade, tumour size, lymph node involvement, oestrogen hormone and HER2 receptor expressions. Various clinical guidelines, prognostic/ predictive tools and tests have been developed to calculate the absolute breast cancer specific survival risks and chemotherapy benefits to help in making the decision of “potential benefit outweighs the potential treatment toxicities” to recommend the adjuvant chemotherapy on individual basis. This principle aims to identify patients with very good prognosis for whom the toxic chemotherapy could be safely omitted and also patients with prognosis poor enough to justify offering toxic chemotherapies. However, no studies have specifically focussed on identifying patients in whom the chemotherapy could not deliver the expected benefit. Analysing molecular biomarker proteins that are functionally important in the cancer biology and chemotherapy cell killing mechanism using readily available and relatively inexpensive immunohistochemistry (IHC) method might be able to identify this Biomarkers to individualise adjuvant systemic therapy in early breast cancer Page 5 group of patients and find the targets against which novel therapy could be developed to improve their survival outcomes.
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Wirth, Manfred, and Michael Fröhner. "A Review of Studies of Hormonal Adjuvant Therapy in Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-134738.
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There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer ProgrammeDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Wirth, Manfred, and Michael Fröhner. "A Review of Studies of Hormonal Adjuvant Therapy in Prostate Cancer." Karger, 1999. https://tud.qucosa.de/id/qucosa%3A27593.
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There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Little, Sarah Ann. "Hepatic malignancy neo-adjuvant therapy and surgical management : clinical and in vivo studies /." Available from the University of Aberdeen Library and Historic Collections Digital Resources. Restricted: no access, contains 3rd party material and therfore cannot be made available electronically, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26220.
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Thesis (M.Phil.)--Aberdeen University, 2008.Title from web page (Viewed on July 29, 2009). With: Improvement in perioperative outcome after hepatic resection : analysis of 1,803 consecutive cases over the past decade / W. R. Jarnagan ... et al Ann. Surg. 2002: 236(4), 397-407. With: Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer / Sarah A. Little ... et al. J. Gastrointest. Surg. 2002: 6, 88-94. With: Tumours of the ampulla and bile ducts / S. A. Little ... et al. in: Current diagnosis and management in gastroenterology / S. L. Friedman, K. R. McQuaid, J. H. Grendell (eds). With: Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholanagiocarcinona : implications for adjuvant therapeutic strategies / S. A. Little ... et al. Cancer: 2003: 15, 98(8) 1689-700. With: Hepatocellular carcinoma : current surgical management / S. A. Little Y. Fong. Seminars in oncology 2001: 28, 5 474-486. With: Neoadjuvant treatment of hepatic malignancy : an oncolytic herpes simplex virus expressing 1L-12 effectively treats the parent tumor and protects against recurrence after resection /W.R. Jarnagin ... et al. Cancer gene therapy. 2003: 10: 215-223. With: The neo-adjuvant combination of an oncolytic HSV-1 with external beam radiation has potent additive effects against a nude mouse model of human cholangiocarcinoma / J. S. Zagwer ... et al. Wangelsteen Surgical Forum. 2001: LII, 252-255. With: Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy / W.R. Jarnagin Cancer gene therapy. 2006: 13, 3, 326-34. Includes bibliographical references.
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Lukefahr, Ashley Leigh. "THE ROLE OF TURMERIC AS AN ADJUVANT THERAPEUTIC FOR OSTEOLYTIC BREAST CANCER BONE METASTASES." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/531833.
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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Zoledronic acid (ZA), the gold standard treatment for breast cancer‐derived osteolytic bone lesions, induces apoptosis in mature osteoclasts. Curcumin, a plant‐dervied component of turmeric (Curcuma longa), inhibits osteoclast differentiation. This study aimed to determine the in vitro and in vivo effects of ZA and curcuminoids, alone and combined, on osteoclast differentiation and survival, breast cancer cell growth, breast cancer cell‐induced osteolytic bone lesion area, and bone mineral density (BMD). Curcuminoids, but not ZA, inhibited osteoclast formation at doses that did not alter precursor viability, as assessed by osteoclastogenesis assays using murine RAW 264.7 cells. Combined curcuminoids and ZA did not differ from curcuminoids alone in their effects on osteoclast survival/formation. The half maximal inhibitory concentration (IC50) for ZA alone was 4 μM, while the IC50 for curcuminoids plus ZA was 6μM. Curcuminoids and ZA inhibit in vitro cell viability of human breast cancer‐ derived MDA‐MB‐231 cells, as assessed by MTT assays. The IC50 of ZA alone was projected to be 1.0677 x 10^4 μM, while the IC50 for curcuminoids alone (9.1 x 10^1 μM), was close to the IC50 for curcuminoids plus ZA (1.31 x 10^2 μM curcuminoids with 300 μM ZA). In vivo effects of ZA (2 μg/kg/d) and curcuminoids (25 mg/kg/d), alone and combined, on osteolytic bone lesions dervied from innoculation with MDA‐MB‐231 cells were assessed. Radiographically‐evident osteolytic bone lesion area did not differ between treatment groups, with a trend towards decreased osteolytic lesion area in mice treated with ZA. BMD In non‐responders, without bone or pericardiac tumors, assessed by dual energy x‐ray absorptiometry, was increased in mice administered ZA. Thus, for the first time, the combined in vitro effects of ZA and curcuminoids on osteclast formation and survival were demonstrated, as well as the combined effects of ZA and curcuminoids on bresat cancer‐derived osteolytic bone lesions and BMD.
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Cardoso, Louro André. "Effects of a positive emotion-based adjuvant psychological therapy in colorectal cancer patients." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/316573.
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The purpose of this study is to examine the effectiveness of a Psychological
Intervention based on the positive psychology and the cognitive behavioral therapy in
relieving “psychological problems” at the time of adjuvant chemotherapy treatment
(Folfox Protocol) in patients with colorectal cancer. This Psychological Intervention is
structured and designed to enhance positive emotions in these patients and will be called
“Enhancing Positive Emotions Procedure” (EPEP). The design of this study was of two
groups with pre-post-test and follow-up comparisons. All participants were recruited
between October of 2012 and February of 2014. 52 subjects diagnosed with colorectal
cancer were recruited at the Portuguese Institute of Oncology, Oporto, Portugal. Results
of this research suggest that some features could be modified by the EPEP procedure,
whereas some others would remain unchanged. Some dimensions of quality of life, as
well as anxiety and positive emotions could be slightly improved by the EPEP Thus,
coping skills and depression would not be affected by the EPEP. Thus, it can be stated,
with caution, that EPEP should be useful to improve well-being in CRC patients
receiving chemotherapy.
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Trabulsi, Nora. "Adherence to adjuvant endocrine therapy in seniors with breast cancer, predictors and challenges." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=117097.
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BACKGROUND: Nearly one-third of breast cancers (BC) occur in women 65 years and older. Anti-estrogen therapy (AET) significantly reduces BC recurrence and death in these patients, as they more often have hormone receptor positive tumors. However, prior studies suggest that adherence to AET in older women is a challenge. OBJECTIVE: To characterize AET adherence in seniors with BC and identify factors influencing it. METHODS: Cancer registry data and administrative claims for all non-metastatic BC diagnosed in Quebec between 1998 and 2005 were accessed from the provincial health insurance program. Patients ≥ 65 years who started AET (Tamoxifen, Anastrozole, Exemestane or Letrozole) and had 5 years of follow up were studied. Five-year medication possession ratio (MPR) was calculated and multivariate linear regression was used to assess the association between patient, disease, and physician characteristics and MPR. RESULTS: 4,715 women were included. Mean age was 72.9. 66.77% had no other significant comorbidities and only 4.16% had 3 or more comorbidities. Stage distribution was: 6.43% in situ, 74.13%localized and 19.45% regional disease. Mean MPR was 83.5% (SD 26.8%). 1596 (34%) women had AET interruption at some point during the entire period of follow up. The cumulative probability of therapy interruption was 33.8% and the mean time to interrupt was 833.4 days. Among those who had therapy interruptions, 39.1% reinstituted AET (mean time to reinstitute was 185.6 days), of which, 48.2% re-interrupted AET again. 5-year MPR decreased with increasing age (p=0.05) and hospitalizations not related to BC (0.73% per each hospitalization, p-value=0.009). Compared to women with node positive disease, those with in situ disease had on average an MPR lower by 6.5%(p-value=0.0003). Having more active prescriptions at baseline increased the MPR by 0.6% for each medication, (p-value< 0.0001). However, adding further new medications after the start of AET affected the MPR negatively (0.3% decrease in MPR for each new medication added, p-value< 0.0001). Among psychotropes, antidepressants were the only group that did show a significant effect, resulting in a MPR decrease of 4.7% among those who were known to take antidepressants prior to the diagnosis and treatment of breast cancer (p-value= 0.003). Women on Tamoxifen, compared to those on Anastrozole, had on average a MPR that is lower by 6%, (p-value= 0.002). Compared to those who never switched their AET type, those who switched early in their treatment course, during the first year, had lower MPR by 5.3% (p-value=0.003). On the other hand, those who switched later had on average an MPR higher by 7.4% (p-value<0.0001). CONCLUSION: Most seniors with BC had high adherence to AET. Patients with more advanced age, less advanced disease and more non-BC related health service use, and women treated with antidepressants prior to their breast cancer were at higher risk of suboptimal adherence.CONTEXTE: Près d'un tiers des cancers du sein surviennent chez les femmesde 65 ans et plus. La thérapie anti-estrogènique (TAE) réduit de manière significative le risque de récidive tumorale et de décès chez les patientes, ayant des tumeurs à récepteurs hormonaux positifs. Cependant, des etudes antérieures suggèrent que l'adhérence à la TAE chez les patientes âgées est sous-optimale. OBJECTIF: Caractériser l'adhérence à la TAE chez les personnes âgées atteintes d'un cancer du sein et identifier les facteurs qui l'influencent. MÉTHODES: Les données du registre du cancer et de reclamations administratives pour tous les cas de cancer du sein non-métastatique diagnostiqués au Québec entre 1998 et 2005 ont été accédées à partir du programme provinciald'assurance-santé. Les patientes âgés de 65 ans ou plus qui ont commencé une TAE (tamoxifène,anastrozole, exémestane oulétrozole) et ont eu 5 ans de suivi ont été étudiées. Le ratio de possession de médicaments à cinq ans (RPM) a été calculé et l'analyse par régression linéaire multivariée a été utilisée pour évaluer l'association entre les caractéristiques des patientes,de leur maladie, les caractéristiques et des médecins traitants. RÉSULTATS: 4,715 femmes ont été inclus. L'âge moyen était de 72,9. 66,77% n'avaient pas d'autres morbidités significatives et seulement 4,16% avaient 3 ou plus des comorbidités. La distribution par stade était: 6,43% in situ, 74.13% cancer localisé et 19.45% maladie régionale. Le RPM moyen était de 83,5% (SD 26,8%). 1596 (34%) des femmes ont eu une interruption de TAE durant la période de suivi. La probabilité cumulée d'interruption était de 33,8% et le temps moyen àa l'interruption était de 833,4 jours. Parmi ceux qui ont subi des interruptions de thérapie, 39,1% ont par la suite réétabli leur TAE (temps moyen de 185,6 jours). De ceux-ci, 48,2% re-interrompu leur TAE. Le RPM avait tendance à diminuer avec l'âge (p = 0,05) et les hospitalisations non-liées au cancer du sein (0,73% pour chaque hospitalisation, p = 0,009). Comparativement aux femmes atteintes d'un cancer à ganglions positifs, celles avec une maladie in situ avaient en moyenne un RPM inférieure de 6,5% (valeur p = 0,0003). Un plus grand nombre de prescriptions actives au depart augmentait le RPM de 0,6% pour chaque médicament, (p <0,0001). Toutefois, l'ajout de nouveaux médicaments après le début de la TAE affectait négativement le RPM (0,3% de baisse en MPR pour chaque nouveau medicament ajouté, p <0,0001). Parmi les psychotropes, les antidépresseurs étaient le seul groupe qui a démontré un impact significatif, entraînant unediminution de 4,7% du RPM chez celles sur antidépresseurs avant le diagnostic et le traitement du cancer du sein (p = 0,003). Les patients sur tamoxifène, comparativement à ceux de l'anastrozole, avaient en moyenne un RPM inférieur de 6%, (p 0,002). Comparé à ceux qui n'ont jamais changé leur type de AET, ceux qui ont changé en début de traitement avaient un RPM plus faible de 5,3% (p = 0,003). D'autre part, celles ayant changé de type de TAE plus tard, avaient en moyenne un RPM supérieur de 7,4% (p <0,0001). CONCLUSION: La plupart des personnes âgées atteintes de cancer du sein hormonosensibl avaient une bonne adhérence à la TAE. Les patientes avec un âge plus avancé, une tumeur précoce, l'usage accru de services de santé, et les femmes traitées avec des antidépresseurs avant leur cancer du sein étaient plus à risque de adhérence sous-optimale.
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Strom, Meghan Brianna. "Dietary Associations with Biomarkers of Breast Cancer Risk in Women on Adjuvant Tamoxifen Therapy." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/612868.
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Dietary components potentially influence breast cancer risk factors, including breast density (BD) and estrogen metabolism (EM). Tamoxifen (TAM) is a commonly prescribed anti-estrogen adjuvant cancer treatment to reduce breast cancer risk, partially through modulation of BD and EM. Epidemiological evidence has suggested a potential protective effect from dietary intakes of fiber and vegetables in breast cancer recurrence in women on TAM as well as an independent influence on BD and EM. The relationship between dietary intake BD and EM in women prescribed TAM is not fully understood. A cross-sectional analysis using baseline data collected from 130 pre- and post-menopausal women taking TAM and enrolled in the Diindolylmethane Efficacy (DIME) Study was conducted. Participants completed the Arizona Food Frequency Questionnaire to assess dietary intake. TAM metabolites were analyzed through HPLC. BD was measured from digital mammograms and urinary EM was analyzed using LC/MS. Unadjusted linear regression between diet and four TAM metabolites indicated significant association between endoxifen and caffeine. 4-hydroxyTAM had significant inverse associations with fat intake, including monounsaturated, polyunsaturated and saturated fats. Linear regression adjusted for BMI revealed a statistically significant positive association with caffeine intake and BD, with no other dietary associations observed. The highest amount of correlations was observed between 2OHE and energy, total fat, MUFA, PUFA, protein and carbohydrate intake, though weak. Correlations were seen between 4OHE, 16αOHE and total isoflavones. Cholesterol was weakly positively correlated with 2mOHE, E1 and approached significance with E2. Dietary intake shows little association with BD or EM in women taking TAM therapy. Alternate preventive mechanisms for diet in women on TAM therapy should be investigated.
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Xu, Fang. "Practice Pattern of Adjuvant Therapy Use in Resectable Colorectal Cancer, A Population Based Study." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301597202.
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Denu, Stefanie. "Impact of Acceptance and Body Compassion in Endometrial Cancer Patients." Xavier University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=xavier1531398277520261.
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LeitÃo, Nilza Maria de Abreu. "Assessment of health-related quality of women with cancer of women with breast and ovarian cancer in adjuvant chemotherapy Life." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=11918.
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This research work aimed to assess the Health-Related Quality of Life of women with breast and gynecological cancer undergoing adjuvant antineoplastic chemotherapy. A descriptive study with cross-sectional design and quantitative approach. The research took place at the chemotherapy ward of a nonprofit tertiary referral hospital for cancer surgery in Fortaleza-CE, Brazil. The study sample consisted of 72 women. Data collection happened from April to May 2012. After given informed consent, all women participated in individual interviews and completed the research protocol consisting of a questionnaire of socio-demographic data and the scale of the European Organization for Research and Treatment of Cancer: Quality of Life Evaluation in cancer patients (QLQ-C30 version 3.0). From the analytical study, we highlight the following results: most patients considered the overall QOL measure as âgreatâ with predominant scores 06 and 07. The sub-scale of the item for Social Functioning had the best score with 54.2. On the other hand, we observed the worst performances of women in the Role Performance, Emotional, Physical, and Cognitive Functioning. Regarding the most frequent or intense symptoms, the most reported were pain, fatigue, insomnia, and loss of appetite. At the opposite extreme were dyspnea, nausea and vomiting, with a mean score of 81.9 and 86.1, respectively. The item relating to Financial Difficulty represented a factor that negatively influences the Quality of Life with representation of 44.4 on the average score. Thus, we conclude that the interaction between clinical situation and treatments for the coexisting disease have cumulative and deleterious effects on Quality of Life, emphasizing the specific concerns related to cancer. It is worth mentioning that the predictive factors for Health-Related Quality of Life identified in this study should receive more attention in the health care practice, they may represent also starting points for future studies that address in depth the different aspects involving the QOL of cancer patients.Este trabalho de investigaÃÃo teve como objetivo avaliar a Qualidade de Vida Relacionada à SaÃde de mulheres com cÃnceres de mama e ginecolÃgico submetidas à quimioterapia antineoplÃsica adjuvante. Estudo de natureza descritiva com delineamento transversal e abordagem quantitativa. O local da pesquisa foi o setor de quimioterapia de uma instituiÃÃo hospitalar filantrÃpica de nÃvel terciÃrio e referÃncia em cirurgia oncolÃgica na cidade de Fortaleza-Ce. A amostra do estudo foi composta por 72 mulheres. A coleta de dados foi realizada no perÃodo de abril a maio de 2012. ApÃs dado o consentimento informado, todas as mulheres participaram de uma entrevista individual e preencheram o protocolo de investigaÃÃo constituÃdo por um questionÃrio de dados sÃcio demogrÃficos e pela escala da European Organization for Research and Treatment of Cancer: AvaliaÃÃo da Qualidade de Vida do doente oncolÃgico (QLQ-C30 versÃo 3.0). Do estudo analÃtico realizado, destacam-se os seguintes resultados: A medida global de QV foi considerado pela maioria como âÃtimaâ com predomÃnio das notas 6 e 7. A sub-escala no item Funcionamento social obteve melhor escore com 54,2. Em contrapartida, os piores desempenhos das mulheres foram observados no nÃvel do Desempenho de PapÃis, Funcionamento Emocional, FÃsico e Cognitivo. Quanto aos sintomas mais frequentes ou intensos foram relatados a dor, fadiga, insÃnia e perda de apetite. No extremo oposto, estavam a dispnÃia, nÃuseas e vÃmitos, com um escore mÃdio de 81,9 e 86,1, respectivamente. O item referente à Dificuldade Financeira mostrou-se como fator que influencia negativamente na Qualidade de Vida com representaÃÃo de 44,4 na mÃdia de escore. Conclui-se que a interaÃÃo entre os quadros clÃnicos e os tratamentos da doenÃa coexistente tem efeitos cumulativos e deletÃrios sobre a Qualidade de Vida, acentuando as preocupaÃÃes especÃficas relacionadas ao cÃncer. Ressalta-se que os fatores preditivos de Qualidade de Vida Relacionada à SaÃde identificados neste estudo devem ser foco de maior atenÃÃo na prÃtica assistencial e podem representar pontos de partida para estudos futuros que abordem, em profundidade, os diferentes aspectos que envolvem a QV de pacientes com cÃncer.
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McAllister, Lauren. "A qualitative investigation of the experiences of women with breast cancer between surgery and adjuvant therapy." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6690/.
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Objectives: The aim of this paper was to explore the experiences of women with breast cancer in the period between surgery and adjuvant chemotherapy or radiotherapy. It also aimed to explore their perceptions of communicating with the professionals involved in their care, and their expectations of adjuvant treatment. Design: Qualitative data were collected through in-depth semi-structured interviews. Methods: Five women were interviewed following surgery and prior to starting adjuvant treatment. Two women were scheduled to receive chemotherapy and three to receive radiotherapy. Interviews were audio-recorded, transcribed verbatim and analysed using Interpretative Phenomenological Analysis. Results: Four themes were identified: uncertainty about adjuvant treatment, adjustment to cancer, knowing enough, and relationships with healthcare professionals. Conclusion: The period between surgery and adjuvant treatment was characterised by uncertainty. This may be adaptive at this point, as it allowed women to maintain hope in the face of potentially unpleasant treatments. Women also continued to adjust to their diagnosis. They wanted to know enough about treatment to prepare themselves, but did not want to be overwhelmed. Women emphasised their own agency in managing information. Healthcare professionals were viewed as a trustworthy source of information, and these relationships supported women's coping in this time period. This study underscores the importance of responding flexibly to women's information and communication needs during treatment.
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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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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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Hanaoka, Nobuharu. "Prognostic Significance of p53 Status in Non-Small Cell Lung Cancer in Correlation with Postoperative Adjuvant Therapy." Kyoto University, 2004. http://hdl.handle.net/2433/148264.
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Maeda, Ryo. "Circulating CD14+CD204+ Cells Predict Postoperative Recurrence in Non-Small-Cell Lung Cancer Patients." Kyoto University, 2016. http://hdl.handle.net/2433/215213.
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Salazar, Marcela d'Alincourt. "Genomic Effects of Hormonal Adjuvant Therapies that Could Support the Emergence of Drug Resistance in Breast Cancer." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1280929084.
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Vexler, Liisa. "Effects of a 12-week walking program on cardiovascular fitness and quality of life in breast cancer patients receiving adjuvant chemotherapy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0003/MQ45254.pdf.
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Sengal, Asmerom Tesfamariam. "Prognostic, predictive, and therapeutic role of FGFR2 isoforms and cognate FGF ligands in endometrial cancer." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/205851/1/Asmerom%20Tesfamariam_Sengal_Thesis.pdf.
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This project investigated the role of FGFR2 isoforms (FGFR2b/FGFR2c) and their cognate FGF ligands in endometrial cancer development, prognosis, and treatment response via designing and validating an innovative BaseScope RNA in-situ hybridization assay and generating patient tumour-derived organoids. FGFR2c and high FGF18 expression were significantly associated with aggressive tumour characteristics and poor survival outcome. It was also noted FGFR2c expression is associated with progestin treatment failure in atypical hyperplasia and well-differentiated endometrial cancers. Overall, FGFR2c and FGF18 are independent prognostic biomarkers that could improve our ability to predict patient prognosis and predict response to FGFR inhibitor treatment in endometrial cancer.
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Bhosle, Monali Jaysing. "Outcomes associated with adjuvant hormonal therapy are there any differences between black and white women with primary breast cancer? /." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1189093998.
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Bhosle, Monali Jaysing. "Outcomes associated with adjuvant hormonal therapy: are they any differences between black and white women with primary breast cancer?" The Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1189093998.
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He, Ru, and 何茹. "Effectiveness and toxicity of aromatase inhabitors [i.e. inhibitors] in adjuvant therapy for hormone receptor positive postmenopausalbreast cancer: a meta-analysis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46936026.
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Enzo, Maria Vittoria. "Analysis of blood-based markers as predicting tools of pathologic tumour response in rectal cancer patients receiving neo-adjuvant chemoradiotherapy." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423392.
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Neo-adjuvant chemo-radio therapy (pCRT) has been accepted as a standard care in the treatment of patients with locally advanced rectal cancer. The multimodality treatment has been established to improve tumour downstaging, pathological complete response, and local disease control. However, the response of individual tumors to the treament is not uniform and ranges from complete response to complete resistance. The discovery of new molecular markers that predict the tumour response is surely of wide interest for personalizing the therapy and reducing time, costs and side effects in the patients with resistant tumours. Many potential biomarkers have been evaluated in order to predict the response to pCRT, and to implement targeted therapeutics. However, single-marker or multi-markers analyses, based on pre-treatment tissue biopsies, often obtained conflicting results demonstrating the heterogeneity of the individual tumour response. Moreover, the prediction of histopathological response to neo-adjuvant treatment is complicated by the interaction and the involvement of the microenvironment in modulating the sensitivity to pCRT. In this study, we developed blood-based methods of biomarker analysis in order to evaluate the histopathological response to treatment in a broad contest that can take into account not only the signalling pathway of tumour cells but also the microenvironment as a part of a unique system. Indeed, the non-invasive nature and the dynamism for which different molecules could be detected according with physiological and pathological states has given us the possibility to monitor the response along the administration of the treatment. In particular, we focused on two different kind of circulating molecules: the cell-free DNA (cfDNA) and the circulating low molecular weight (LMW) peptides. In particular, we investigated the presence, the quantity of cfDNA and its integrity (cfDNA integrity = non apototic cfDNA / total cfDNA) along the chemo-radio treatment. For this purpose we measured the cfDNA concentration and cfDNA integrity in a prospective study of locally advanced rectal cancer patients plasma collected before the pCRT, after two weeks from initiation of the pCRT and after the pCRT. We evaluated the association of these markers with the histological response to the chemo-radio therapy, demonstrating a different kinetic of cfDNA integrity in association with the tumour response.
Then we studied the LMW peptidome circulating in plasma, in order to find evidences of possible differences in the peptide profile that could reflect the tumour response. To overcome the technical difficulties in harvesting LMW species, we have employed the mesoporous chip-based technology, developed by the Nanomedicine Department of The Methodist Hospital Research Institute in Houston, Texas. This mesoporous device, in combination with matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS), allows the isolation and the detection of small peptides from the large proteins. We analyzed plasma of rectal cancer patients, with positive or negative response to the therapy, at the same time points as the cfDNA: before, during, after the chemo-radio therapy. Multivariate analyses of the LMW peptide profile at different time points identified combinations of peptides that revealed high discriminating capacity of the different tumour responses. In particular, before the pCRT, a pattern of five ionic species showed a sensitivity and a specificity of 80% and after the pCRT, a pattern of other five specific ionic species showed a sensitivity of 80% and a specificity of 85% to cluster patients on the basis of histopathologic response to pCRT. Moreover the identification of the amino acids sequences of the response-specific ionic species revealed the presence of protein fragments that could be directly or indirectly valuable for further investigation on the resistance mechanisms of the rectal tumour to the neo-adjuvant chemo-radio therapyLa radiochemioterapia neoadiuvante (pCRT) è un protocollo standard accettato per il trattamento di pazienti con cancro rettale localmente avanzato. Il trattamento preoperatorio multimodale è stato introdotto per la riduzione dello stadio del tumore, per l’aumento della risposta completa patologica e per il controllo locale della malattia. Tuttavia la risposta patologica al trattamento non è uniforme e varia da una risposta completa alla resistenza totale. La scoperta di nuovi marcatori molecolari in grado di predire la risposta del tumore è sicuramente di grande interesse al fine di personalizzare la terapia, riducendo così i tempi, i costi e gli effetti collaterali nei pazienti con tumori resistenti. Molti potenziali biomarcatori sono stati valutati con l’obiettivo di prevedere la risposta alla pCRT, e di attuare terapie mirate. Finora molti studi su singolo o multi-marcatore sono stati eseguiti prevalentemente su biopsie di tessuto pre-trattamento. I risultati ottenuti, tuttavia, erano spesso contrastanti dimostrando l'eterogeneità individuale della risposta tumorale al trattamento. Inoltre, la predizione della risposta istopatologica alla pCRT è complicata dall’interazione e dal coinvolgimento del microambiente che può modulare la sensibilità del tumore al trattamento. In questo studio, abbiamo sviluppato metodi di analisi di biomarcatori su sangue, al fine di valutare la risposta del tumore al trattamento in un contesto più ampio, che rende conto non solo dell’ambiente strettamente tumorale, ma che prende in considerazione anche il microambiente come parte di un sistema unico. Infatti, la natura non invasiva del materiale biologico analizzato e il dinamismo per cui molecole differenti possono essere rilevate secondo lo stato fisiologico e patologico dell’organismo, ci hanno permesso di monitorare la risposta lungo il tempo di somministrazione del trattamento. In particolare, ci siamo concentrati su due diversi tipi di molecole circolanti: il DNA libero da cellule (cfDNA) e i peptidi a basso peso molecolare (Low Molecular Weight, LMW). In particolare, abbiamo studiato la presenza, la quantità e l’integrità del cfDNA durante il trattamento radio-chemioterapico. A questo scopo abbiamo misurato la concentrazione e l'integrità del cfDNA (cfDNA integrity=cfDNA apoptotico/cfDNA totale) in uno studio prospettico di plasma di pazienti con carcinoma rettale localmente avanzato, raccolto prima della pCRT, dopo due settimane dall'inizio del trattamento e dopo la pCRT. Abbiamo valutato l'associazione di questi marcatori con la risposta istologica alla chemio-radio terapia, dimostrando la presenza di diversa cinetica nell’integrità del cfDNA, in associazione con la risposta tumorale. Nel plasma, abbiamo quindi studiato il peptidoma circolante a basso peso molecolare, al fine di trovare potenziali differenze nel profilo peptidico che potessero riflettere la risposta tumorale. Per superare le difficoltà tecniche nella rilevazione dei peptidi circolanti a basso peso molecolare, abbiamo utilizzato una strategia basata sull’esclusione dimensionale di un chip di silice mesoporosa (MSC), sviluppato dal Dipartimento Nanomedicina del The Methodist Hospital Research Institute di Houston, Texas. Questo dispositivo mesoporoso, in combinazione con l’utilizzo dello spettrometro di massa MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry), consente l'efficiente rimozione di grandi proteine e l'isolamento del peptidoma circolante da campioni di fluidi corporei. Abbiamo analizzato il plasma di pazienti con cancro rettale, prelevato in diversi tempi (prima, durante, dopo la chemio-radio terapia) e stratificati secondo la risposta positiva o negativa alla pCRT. L'analisi multivariata del profilo peptidico nei diversi tempi di analisi ha identificato combinazioni di peptidi che evidenziavano un’elevata capacità discriminante della risposta tumorale. In particolare, il modello di regressione logistica ha evidenziato, prima della pCRT, una combinazione di cinque specie ioniche capace di identificare i pazienti che non rispondono al trattamento, con una sensibilità e una specificità del 80%; mentre la stessa analisi con i campioni raccolti dopo la pCRT, ha identificato un'altra combinazione di cinque specie ioniche che evidenziano una sensibilità del 80% e una specificità del 85%. Inoltre, l'identificazione delle sequenze amminoacidiche di alcune tra le specie ioniche discriminanti la risposta alla pCRT, hanno rivelato la presenza di frammenti proteici che possono essere direttamente o indirettamente utili per ulteriori indagini sui meccanismi di resistenza del tumore rettale alla radio-chemio terapia neo-adiuvante
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Patel, Rikesh. "An observational pilot study to assess the potential of a microfluidic tissue culture model to predict rectal cancer response to neo-adjuvant therapy." Thesis, University of Hull, 2016. http://hydra.hull.ac.uk/resources/hull:14518.
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Radiotherapy has been reported to induce apoptosis and prevent the proliferation of malignant cells. Complete clinical response to neo-adjuvant long course chemoradiotherapy has been identified in up to 30% of patients with locally advanced rectal cancer. The aim of this study was firstly to maintain rectal cancer biopsies in a viable state within a microfluidic device and subsequently interrogate this ex vivo rectal cancer tissue with radiation and measure changes in morphology and induction of cell death through apoptosis. Murine colorectal tissue was used for initial optimisation, followed by biopsies from patients with locally advanced rectal cancer taken prior to neo- adjuvant therapy. This tissue was maintained in a biomimetic environment within a bespoke, glass microfluidic device. Subsequently, murine tissue was interrogated with single fractions of radiation (2Gy, 10Gy or 30Gy) to identify suitable doses for delivery to human tissue. Morphology was assessed using H&E staining of the tissue. Effluent from the tissue was collected for subsequent analysis of cell death using a lactate dehydrogenase (LDH) assay and metabolite release using a mass spectrometry-metabolomics approach. Apoptosis was evaluated using the M30 CytoDeath™ monoclonal antibody and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay to identify DNA fragmentation. Tissue was successfully maintained for over 70 hours with evidence of viability, as determined by preservation of morphology and increased LDH release after lysis. Rectal cancer biopsies (n = 11 patients) were subsequently interrogated with radiation. Only high doses of radiation (30Gy) delivered to murine colorectal tissue reproducibly induced high levels of LDH release, however architectural losses were seen in all tissue after irradiation regardless of dose. Human tissue was therefore irradiated with 2Gy as an approximation of the dose delivered clinically. Levels of apoptosis using M30 CytoDeath™ ELISA were not significantly increased in the irradiated groups when compared to control groups. However, using immunohistochemical assessment with M30 CytoDeath™ and TUNEL, significant increases in the irradiated groups were seen (p < 0.05). Evaluation of individual patients using these markers identified several patients with significant rises (p < 0.05) in levels of apoptosis, however there was no correlation with clinical response. Metabolomic analysis identified 28 differentially expressed (p < 0.0001) compounds in effluents collected prior to and after irradiation, however this appeared to be a time-dependent effect, rather than due to irradiation. This work has demonstrated that the microfluidic device can be used to reliably maintain both ex vivo healthy murine colorectal and human rectal cancer tissue for a sufficient period of time to permit interrogation with radiation. Findings demonstrated that apoptosis and morphological changes are induced by irradiation. Further work is required to correlate findings with clinical outcome, but important progress has been made to allow use of this platform as a predictive tool of response to neo-adjuvant therapy to deliver personalised therapy.
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Waeber, Martin Andreas. "Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence : definitive results of a phase III randomized trial comparing tamofixen with observation /." Bern : [s.n.], 2003. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Heinen, Tiago Elias. "Potencial terepêutico de inibidores de TRK no tratamento de sarcoma de Ewing : um estudo celular e molecular." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/150631.
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O sarcoma de Ewing (SE) é um dos mais agressivos tipos de câncer pediátrico. Apesar dos significativos avanços no tratamento dessa doença, ainda há uma grande necessidade no aumento das taxas de cura, redução da toxicidade quimioterápica e redução da resistência ao tratamento. Tem sido proposto que SE provém de precursores neuronais, podendo ter sua fisiologia afetada, pois, por neurotrofinas (NTs). Examinamos a influência de receptores de NTs (Trks) em SE. Foram avaliadas a expressão proteica de NTs (NGF e BDNF) e seus receptores (TrkA e TrkB, respectivamente) em amostras de tumores de pacientes com SE, e a expressão de mRNA nas linhagens celulares RD-ES e SK-ES-1. O tratamento das linhagens com o pan-inibidor de Trks (K252a) modificou a morfologia celular e diminuiu a expressão de mRNA de NGF, TrkA, BDNF e TrkB. Ainda, a inibição de Trks diminuiu drasticamente a proliferação e capacidade clonogênica celular. Efeitos sinérgicos foram observados quando as células foram tratadas em conjunto com baixas doses de quimioterápicos, tanto em células selvagens de SE, quanto nas quais induzimos quimiorresistência. Esse estudo sugere, pela primeira vez, que a inibição de Trks reduz a proliferação e sobrevivência celular em SE, além de aumentar a sensibilidade ao tratamento quimioterápico.Ewing's sarcoma (ES) is one of the most aggressive types of pediatric cancer. Despite significant advances in the treatment of this disease, there is still a great need in increasing cure rates, reducing chemotherapy toxicity and treatment resistance. It has been proposed that ES might derive from neuronal precursors and may be influenced, therefore, by neurotrophins (NTs). We have examined the influence of Trk neurotrophin receptors in ES. Protein expression of NTs (NGF and BDNF) and their receptors (TrkA, and TrkB, respectively) was detected in tumor samples from patients with ES, and mRNA expression was analyzed in the RD-ES, SK-ES-1 cell lines. Treating cells with a Trk Pan-inhibitor (K252a) altered cell morphology and decreased the mRNA expression of NGF, TrkA, BDNF, and TrkB. In addition, Trk inhibition dramatically decreased cell proliferation and clonogenic capacity. Synergistic effects were observed when cells were treated in combination with low doses of cytotoxic chemotherapeutics, both in normal ES cells and cells in which chemoresistance was induced. The results suggest for the first time that Trk inhibition can reduce the proliferation and survival of ES cells and sensitize them to cytotoxic chemotherapy.
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Van, Jaarsveld Albert. "The role of adjuvant radiotherapy for breast cancer patients with axillary node negative or limited nodal disease after total mastectomy, axillary nodal clearance and systemic therapy." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/5931.
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Wirth, Manfred. "Delaying/Reducing the Risk of Clinical Tumour Progression after Primary Curative Procedures." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-134720.
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The advent of prostate-specific antigen (PSA) testing and increased patient awareness has led to patients being diagnosed with prostate cancer at an earlier stage and a younger age than previously. Adjuvant hormonal therapy to radiotherapy or prostatectomy has been shown to reduce the risk of tumour progression, and in some studies survival benefits have been demonstrated. The non-steroidal antiandrogen bicalutamide (‘Casodex’) has undergone extensive evaluation and is currently undergoing clinical trials as immediate therapy, either alone or as adjuvant to treatment of curative intent in patients with localized or locally advanced disease. Data from the first analysis of one of the studies in the Early Prostate Cancer (EPC) programme involving 3,603 patients have shown that, after a median follow-up of 2.6 years, the risk of prostate cancer progression was significantly reduced (by 43%) in patients receiving bicalutamide 150 mg compared with those receiving standard care alone (HR 0.57; 95% CI 0.48, 0.69; p ≪ 0.0001). The risk of PSA progression was also significantly reduced (by 63%). At this stage the survival data are still immature. Side effects of bicalutamide were mostly gynaecomastia and breast pain, which is consistent with its pharmacology. Overall withdrawal rates were similar in the bicalutamide 150 mg and standard care alone groups. In the bicalutamide 150 mg group, withdrawals were mainly due to side effects, whereas in the group receiving standard care alone, withdrawals were mainly due to disease progression. The programme is ongoing, and survival data are awaitedDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Reddy, Bhiskar. "Dosimetric comparison of volumetric modulated arc therapy and three dimensional conformal radiotherapy in the adjuvant setting for the management of gastric cancer : target volume coverage and normal tissue sparing." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/12943.
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Includes bibliographical references.Whilst the benefit of adjuvant radiotherapy in gastric cancer is known, the optimal means of delivery, including two dimensional conventional, three dimensional conformal radiotherapy, intensity modulated radiotherapy and volumetric modulated arc therapy is less certain. The purpose of this study is to assess and compare volumetric modulated arc therapy (VMAT) and three dimensional conformal radiotherapy (3DCRT) plans in adjuvant radiation of gastric cancer.
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Mercatali, Laura <1977>. "Evaluation of Antitumoral activity of bone targeted drugs/conventional chemotherapies and identification of biomarkers for the selection of patients with breast cancer for the bone targeted therapy in adjuvant setting." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6394/1/Mercatali_Laura_tesi.pdf.
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Bone metastases are responsible for different clinical complications defined as skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, hypercalcaemia, bone marrow infiltration and severe bone pain requiring palliative radiotherapy. The general aim of these three years research period was to improve the management of patients with bone metastases through two different approaches of translational research. Firstly in vitro preclinical tests were conducted on breast cancer cells and on indirect co-colture of cancer cells and osteoclasts to evaluate bone targeted therapy singly and in combination with conventional chemotherapy. The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Furthermore the combination Zoledronic Acid + Cisplatin induced a high antitumoral activity in the two triple-negative lines MDA-MB-231 and BRC-230. The p21, pMAPK and m-TOR pathways were regulated by this combined treatment, particularly at lower Cisplatin doses. A co-colture system to test the activity of bone-targeted molecules on monocytes-breast conditioned by breast cancer cells was also developed.
Another important criticism of the treatment of breast cancer patients, is the selection of patients who will benefit of bone targeted therapy in the adjuvant setting. A retrospective case-control study on breast cancer patients to find new predictive markers of bone metastases in the primary tumors was performed. Eight markers were evaluated and TFF1 and CXCR4 were found to discriminate between patients with relapse to bone respect to patients with no evidence of disease. In particular TFF1 was the most accurate marker reaching a sensitivity of 63% and a specificity of 79%. This marker could be a useful tool for clinicians to select patients who could benefit for bone targeted therapy in adjuvant setting.
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Mercatali, Laura <1977>. "Evaluation of Antitumoral activity of bone targeted drugs/conventional chemotherapies and identification of biomarkers for the selection of patients with breast cancer for the bone targeted therapy in adjuvant setting." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6394/.
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Bone metastases are responsible for different clinical complications defined as skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, hypercalcaemia, bone marrow infiltration and severe bone pain requiring palliative radiotherapy. The general aim of these three years research period was to improve the management of patients with bone metastases through two different approaches of translational research. Firstly in vitro preclinical tests were conducted on breast cancer cells and on indirect co-colture of cancer cells and osteoclasts to evaluate bone targeted therapy singly and in combination with conventional chemotherapy. The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Furthermore the combination Zoledronic Acid + Cisplatin induced a high antitumoral activity in the two triple-negative lines MDA-MB-231 and BRC-230. The p21, pMAPK and m-TOR pathways were regulated by this combined treatment, particularly at lower Cisplatin doses. A co-colture system to test the activity of bone-targeted molecules on monocytes-breast conditioned by breast cancer cells was also developed.
Another important criticism of the treatment of breast cancer patients, is the selection of patients who will benefit of bone targeted therapy in the adjuvant setting. A retrospective case-control study on breast cancer patients to find new predictive markers of bone metastases in the primary tumors was performed. Eight markers were evaluated and TFF1 and CXCR4 were found to discriminate between patients with relapse to bone respect to patients with no evidence of disease. In particular TFF1 was the most accurate marker reaching a sensitivity of 63% and a specificity of 79%. This marker could be a useful tool for clinicians to select patients who could benefit for bone targeted therapy in adjuvant setting.
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Wirth, Manfred. "Delaying/Reducing the Risk of Clinical Tumour Progression after Primary Curative Procedures." Karger, 2001. https://tud.qucosa.de/id/qucosa%3A27591.
Full textAbstract:
The advent of prostate-specific antigen (PSA) testing and increased patient awareness has led to patients being diagnosed with prostate cancer at an earlier stage and a younger age than previously. Adjuvant hormonal therapy to radiotherapy or prostatectomy has been shown to reduce the risk of tumour progression, and in some studies survival benefits have been demonstrated. The non-steroidal antiandrogen bicalutamide (‘Casodex’) has undergone extensive evaluation and is currently undergoing clinical trials as immediate therapy, either alone or as adjuvant to treatment of curative intent in patients with localized or locally advanced disease. Data from the first analysis of one of the studies in the Early Prostate Cancer (EPC) programme involving 3,603 patients have shown that, after a median follow-up of 2.6 years, the risk of prostate cancer progression was significantly reduced (by 43%) in patients receiving bicalutamide 150 mg compared with those receiving standard care alone (HR 0.57; 95% CI 0.48, 0.69; p ≪ 0.0001). The risk of PSA progression was also significantly reduced (by 63%). At this stage the survival data are still immature. Side effects of bicalutamide were mostly gynaecomastia and breast pain, which is consistent with its pharmacology. Overall withdrawal rates were similar in the bicalutamide 150 mg and standard care alone groups. In the bicalutamide 150 mg group, withdrawals were mainly due to side effects, whereas in the group receiving standard care alone, withdrawals were mainly due to disease progression. The programme is ongoing, and survival data are awaited.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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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
Made available in DSpace on 2018-08-27T13:13:47Z (GMT). No. of bitstreams: 1 Duarte_IgorLemos_M.pdf: 729678 bytes, checksum: 3da7b8934fdc3f3c7776ad13bc0dbd2b (MD5) Previous issue date: 2015
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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Oettle, Helmut. "Entwicklung von neuen Behandlungskonzepten zur Therapie des Pankreaskarzinoms." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2002. http://dx.doi.org/10.18452/13797.
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Jährlich erkranken in Deutschland über 11.000 Patienten an Pankreaskarzinomen. Für die ganz überwiegende Mehrzahl dieser Patienten ist die Diagnosestellung gleichbedeutend mit einem Todesurteil innerhalb von wenigen Wochen, hauptsächlich bedingt durch das meist fortgeschrittene Krankheitsstadium bei Diagnosestellung sowie die relative Therapieresistenz des Tumors. Die vorliegende Arbeit faßt wissenschaftliche Untersuchungen zusammen, die in den zurückliegenden vier Jahren in Berlin zu dieser Thematik durchgeführt wurden. Stadienadaptiert wurden Behandlungskonzepte und klinische Studien entwickelt und durchgeführt, die von der adjuvanten Chemotherapie über ein Radiochemo-therapiekonzept bei lokal fortgeschrittenen Stadien hin zur Entwicklung einer neuen Zytostatika-Kombinationstherapie für die Behandlung metastasierter Pankreastumoren im Rahmen einer multinationalen Phase III Studie geführt haben. Neben diesen Schemata konnte auch eine wirksame Zweitlinientherapie geprüft werden. An Tumormaterial konnte gezeigt werden, daß sich keine Her2/neu-Überexpressionen bei Pankreastumoren nachweisen lassen, die therapeutisch nutzbar wären. Bei ca. 80 % aller Pankreaskarzinome lassen sich Mutationen des K-ras-Onkogens nachweisen. In Kooperation mit einer anderen Arbeitsgruppe wurde ein Verfahren entwickelt, mit dem sich qualitativ und semiquantitiativ schnell und zuverlässig ras-Mutationen nachweisen lassen. Diese klinischen Studienergebnisse geben Grund zur Hoffnung, die Prognose von Patienten mit Pankreaskarzinomen in den nächsten Jahren durch die hier vorgestellten Konzepte zu verbessern. Fortschritte im Verständnis der molekularen Karzinogenese, in Diagnostik und Therapie lassen in naher Zukunft Ergebnisse erwarten, die zumindest denen bei anderen soliden Tumoren nahekommen. Daher ist der vereinzelt noch verbreitete therapeutische Nihilismus bei der Behandlung des Pankreaskarzinoms als nicht länger gerechtfertigt und akzeptabel anzusehen.In Germany, more than 11,000 patients are diagnosed with pancreatic cancer each year. For the vast majority, this means a death verdict within a few weeks, primarily due to the advanced stage of the disease at diagnosis and the relative chemoresistance of the tumor. This thesis summarizes the scientific work regarding pancreatic cancer that has been done within the last four years. Several clinical treatment concepts and studies were developed and conducted that covered the different stages of the disease, including adjuvant therapy, radiochemotherapy for locally advanced disease and a multinational phase III study for the patients with metastatic disease. In addition, an effective second line regimen was developed. Using tumor material, we found no overexpression of Her2/neu which would have been a therapeutically usable target. Mutations of the K-ras oncogene can be found in approximately 80% of patients with pancreas carcinoma. A method for a rapid and reliable qualitative and semiquantitative determination detection of ras mutations was developed in cooperation with another research group. The clinical results give rise to the hope that the prognosis of patients with pancreatic carcinoma can be improved during the next years using the concepts outlined above. Recent improvements in our understanding of the molecular carcinognesis together with advances in diagnostics and therapy give rise to the expectation that clinical results will be achievable that will be at least as good as those for other solid tumors. Therefore, nihilism regarding the treatment of pancreatic cancer that still can be found is no longer justifiable or acceptable.
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Dehkhoda, Farhad. "Identification and validation of FGFR2 mutations providing resistance to pan-FGFR inhibitor BGJ398." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/114506/1/Farhad%20Dehkhoda%20Thesis.pdf.
Full textAbstract:
Endometrial cancer (EC) is the most commonly diagnosed gynaecological cancer, and is responsible for ~370 deaths per year in Australia and 8600 deaths annually in the USA. Fibroblast growth factor receptor 2 (FGFR2) mutations have been identified in ~ 12% of endometrial cancer patients and research confirms it is a valid therapeutic target. Tyrosine kinase inhibitors (TKIs) have been used in the last few years to treat patients with mutant receptor tyrosine kinases (RTKs). Despite patients showing an initial response to these TKIs, acquired resistance associated with cancer relapse often occurs. Acquired resistance is frequently caused by secondary mutations in the kinase domain that either directly hinder drug binding or stabilise a conformation not conducive to drug binding.
In recent years, the Ba/F3 cell line model system has been used to identify mutations causing resistance to these inhibitors and many of these mutations have subsequently been identified in patients treated with these TKIs. We sought to identify FGFR2 kinase domain mutations that confer resistance to the pan-FGFR inhibitor BGJ398. We cultured Ba/F3 cells expressing FGFR2 in high doses of BGJ398 and identified 6 resistant clones harbouring either the FGFR2E566A or FGFR2V565I mutations in the kinase domain. Ba/F3 cells carrying each mutations, together with the FGFR2N550K mutation commonly seen in patients, were used to assess if these mutations were cross-resistant to other FGFR inhibitors (PD173074, ponatinib, AZD4547 and LY2874455). Only LY2874455 inhibited all the resistant FGFR2 mutations. In addition, lentiviral transduction of the endometrial cancer cell line JHUEM2 with the same FGFR2 resistance mutations resulted in heterozygous expression of the resistance alleles confirmed by sequencing cDNA. Transduced JHUEM2 cell lines were tested against the panel of FGFR inhibitors, however, the same level of resistance that was seen in Ba/F3 cells was not always observed in the JHUEM2 cell lines. We also used the myeloma cell line KMS11-R, which harbours a heterozygous FGFR3V565I mutation, and showed these cells conferred resistance to all inhibitors except LY2874455. From these data we propose that tumours harbouring FGFR mutations should be treated with LY2874455, as it effectively inhibits all identified FGFR mutations that cause resistance to other FGFR inhibitors.
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Lux, Michael P., Achim Wöckel, Agnes Benedict, Stefan Buchholz, Noémi Kreif, Nadia Harbeck, Rolf Kreienberg, et al. "Cost-Effectiveness Analysis of Anastrozole versus Tamoxifen in Adjuvant Therapy for Early-Stage Breast Cancer – a Health-Economic Analysis Based on the 100-Month Analysis of the ATAC Trial and the German Health System." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-134902.
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Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifenHintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Lux, Michael P., Achim Wöckel, Agnes Benedict, Stefan Buchholz, Noémi Kreif, Nadia Harbeck, Rolf Kreienberg, et al. "Cost-Effectiveness Analysis of Anastrozole versus Tamoxifen in Adjuvant Therapy for Early-Stage Breast Cancer – a Health-Economic Analysis Based on the 100-Month Analysis of the ATAC Trial and the German Health System." Karger, 2010. https://tud.qucosa.de/id/qucosa%3A27603.
Full textAbstract:
Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen.Hintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Skírnisdóttir, Ingirídur. "Prognostic Factors in Early Stages (FIGO I-II) of Epithelial Ovarian Carcinoma." Doctoral thesis, Uppsala University, Department of Women's and Children's Health, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1729.
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From January, 1988, to December, 1993, 113 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. The median follow-up period was 74 months. Tumor recurrences were recorded in 33 cases (30%). The cancer-specific survival rate was 72%. Tumor grade was a significant (P = 0.007) and independent prognostic factor in the multivariate analysis. In a smaller series of 106 patients, a number of prognostic factors (age, FIGO stage, histopathological type, and tumor grade) were studied in relation to regulators of apoptosis (p53, bcl-2, and bax) and growth factor receptors (HER-2/neu and EGFR). Immunohistochemical techniques were used. In a separate series of 103 patients, the DNA content (flow cytometry) and p53 status of the tumors were also studied and related to the same clinicopathological factors. P53 was associated with tumor grade (P = 0.007) and survival status (P = 0.046). In a Cox multivariate analysis, tumor grade (P = 0.0006), bax status (P = 0.020), and EGFR status (P = 0.018) were significant and independent prognostic factors. DNA ploidy of the tumors was strongly associated with tumor grade.
From January, 1994, to December, 1998, a series of 109 patients with ovarian carcinomas (FIGO IA-IIC) were treated with postoperative adjuvant chemotherapy. The same prognostic factors were studied in this series. The median follow-up was 48 months and the cancer-specific survival rate was 75%. Twenty-five (25%) tumor recurrences were recorded. The most favorable survival rate was seen in patients with tumors negative for p53 and positive for bcl-2 or bax. In a multivariate analysis, tumor grade (P = 0.014) and p53 status (P = 0.020) were independent prognostic factors.
Clinical, histopathological and biological prognostic factors should be combined in prognostic models to render patient-tailored therapy possible and to define different prognostic groups for future clinical studies of adjuvant therapy in early stage ovarian carcinomas.
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Ping, Chen Chun, and 陳君萍. "Weight change associated with adjuvant tamoxifen therapy in breast cancer." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/40055772257823152856.
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CHENG, WEN-HSUEN, and 鄭文雪. "The Experience of Adjuvant Hormonal Therapy in Women with Breast Cancer." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/49832653497228692742.
Full textAbstract:
碩士國立台北護理學院
護理研究所
98
This study was conducted by the method of qualitative analysis of the data collected by in-depth interviews of the women with breast cancer who were taking adjuvant hormonal therapy. The qualitative analysis used constant comparative method for data collection and subsequent data analysis. The target population of this study were women with confirmed pathological diagnosis of breast cancer, regardless of whether she had received chemotherapy in the past; who’s currently receiving adjuvant oral hormonal therapy for at least six months, and was willing to share their experience by participating in this study. This study collected data from a total of 11 cases. The researcher was the data collector. The research tools involved the general information of each case and the open-ended interview guide. Participants decided where and when the interview took place. Data was collected by in-depth face to face interview and the content was recorded by a voice recorder. The average time for each interview was about 65 minutes. For insuring the validity of this study, the method developed by Lincoln and Guba (1985) was used to evaluate and confirm the credibility, transferability, dependability, and confirmability of the study. The results of this study covered three aspects of the experience of the breast cancer patients who received adjuvant hormonal therapy, which includes: the experience of coexistence with the medication, life style adjustment after taking the medication, and restructuring for the meaning of life. Hopefully, this study will raise the cognition of the medical staff for the the experience of adjuvant hormonal therapy in women with breast cancer and provide a comprehensive and holistic patient care.
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Huang, Chiung-Hsuan, and 黃瓊萱. "The Health Needs among Breast Cancer Women Receiving Adjuvant Hormonal Therapy." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/10191090706627615785.
Full textAbstract:
碩士國立台北護理學院
護理研究所
95
Breast cancer patients undergoing adjuvant hormone therapy is increasing recently. The health needs of these patients have their specific health concerns, such as the management of their menopausal symptoms. However, little studies were conducted in Taiwan. The purposes of this study were to explore the health needs and related factors such as demographic data, health status and menopausal disturbance symptoms among breast cancer patients undergoing adjuvant hormone therapy in Taiwan. Sixty-five women were recruited. The collected data were analyzed through the statistical software, SPSS 14.0. The findings of this study were as follows: 1.The mean age of the women was 48.40. The average time of post-operation was 2.40 years. All women were undergoing the adjuvant hormone therapy. Average duration of using adjuvant hormone therapy was 1.89 years. 75% of the women have received chemotherapy and 47.69% of women have been treated by radiotherapy. 2.The satisfaction level of the holistic health needs was at the level of moderate to good. The order of satisfaction level of the health needs was: psychosocial support needs, information needs and physical needs. The top five issues of un-meted health needs were: “how to prevent from menopausal heart diseases”, “how to manage menopausal symptoms such as bone and joint, mental and vasomotor symptoms” and “How to use complimentary and alterative therapy to prevent from breast cancer recurrence”. Women expressed that they needed the knowledge of prevent from breast cancer recurrence and body discomforts such as insomnia, hot flash and joint pain during receiving hormone therapy. 3.Women reported that their health status were worse than before. Self-perceived health status was at moderate good level. The women perceived occasionally negative feelings. There is little influences on daily activity except the exertion of cleaning, wiping the floor, carrying heavy bag. The women expressed that their menopausal disturbance symptoms were at ‘mild’ disturbcance level. The rank of menopausal disturbances symptoms was: sleep disturbance, difficulty in falling asleep, forgetfulness, insufficient sleep and irregular menses. 4.The satisfactions of the holistic health needs were positively related with the time of using hormone therapy, self-perceived mental health status and menopausal disturbance symptoms and negatively related with menopausal disturbance symptoms. 5.The mental health status, reproductive menopausal symptoms and time of using adjuvant hormone therapy explained 47.5% of the variance of the satisfaction of holistic health needs. This study suggests health providers to provide active support and information to breast cancer women about possible menopausal symptoms and how to prevent from the recurrence of breast cancer including self-examination of recurrence symptoms, complimentary and alterative therapy.
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Chao, Yu-Fen, and 趙雨芬. "Urinary Incontinence among Women with Adjuvant Endocrine Therapy after Breast Cancer." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/02530570697035464190.
Full textAbstract:
碩士國立臺灣大學
物理治療學研究所
103
Background: Hormone therapy is a postoperative adjuvant treatment of breast cancer, side effects may occur due to estrogen deprivation. Various studies have documented the prevalence and severity of menopausal symptoms, such as: vaginal dryness, discharge and dyspareunia, in breast cancer patients with adjuvant endocrine therapy. However, urinary incontinence as a part of menopausal symptoms has received little attention. Purpose: This study aims to investigate the prevalence and severity of urinary incontinence symptoms and its impact on quality of life (QoL) in breast cancer patients with adjuvant endocrine therapy and non- users; and to compare the differences between the groups. Methods: A cross-sectional survey study was conducted using a structured validated questionnaires, including the Urinary Distress Inventory-6 (UDI-6), Incontinence Impact Questionaire-7 (IIQ-7) and King''s Health Questionnaire (KHQ) to investigate the prevalence, severity of urinary incontinence (UI) and QoL in breast cancer patients with adjuvant endocrine therapy and age-matched non- users. Descriptive statistics was computed for subject demographics. Independent t- tests or Mann-Whitney U test were performed to compare the basic data of two groups. Frequencies were compared between groups by chi-square test. Results: A total of 140 breast cancer women were surveyed, 70 breast cancer patients taking tamoxifen and 67 controls. Tamoxifen-treated group had significantly more incontinent women than control group (42.9% vs 20.9%，p < 0.05); of these, stress UI was the most common symptom (63%). In addition, the domain of UDI-6 concerning irritative symptoms (e.g., frequency and urgency) was significantly poorer in tamoxifen- treated patients than in control group (p < 0.05). In the KHQ, the sleep/energy and gravity domains was significantly affected in tamoxifen-treated incontinent women than control group (p < 0.05). Discussion and Conclusion: This was a preliminary study using a validated questionnaire to assess the prevalence of incontinence and the impact on HRQOL in tamoxifen users. Tamoxifen was found to increase urinary incontinence compared with non-users of tamoxifen; and incontinence symptoms tend to be mild in severity. In addition, incontinence can have a negative impact on daily life. It is therefore possible that estrogen deficiency induced by tamoxifen plays an etiological role in the development of UI. Frequent monitoring of the presence and severity of incontinence symptoms and treatment of these bladder problems is required to optimize patient quality of life and to assure adherence to endocrine therapy.
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Barros, Gabriela Correia. "Photodynamic therapy as an innovative approach to Endometrial Cancer Stem Cells." Master's thesis, 2021. http://hdl.handle.net/10316/98014.
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Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e TecnologiaO cancro do endométrio (EC, do inglês Endometrial Cancer) representa cerca de 6% dos cancros no sexo feminino, sendo a doença maligna ginecológica mais frequente em países desenvolvidos. A cirurgia radical é o tratamento primário mas em mulheres jovens ou em doentes com elevado risco cirúrgico pode não ser uma opção. Além disso, métodos conservadores convencionais apresentam riscos inerentes, incluindo ineficácia e a possibilidade de recorrência. Estes factos suportam a necessidade de explorar novas abordagens conservadoras para o EC. A terapia fotodinâmica (PDT, do inglês Photodynamic Therapy) é um tratamento minimamente invasivo que pode ser considerado para a preservação da fertilidade. O nosso grupo de investigação desenvolveu recentemente umas novas clorinas muito promissoras que podem ser usadas como fotossensibilizadores em PDT. As clorinas fundidas com anel 4,5,6,7-tetra-hidropirazolo[1,5-a]piridina e as clorinas fundidas com anel 4,5,6,7-tetra-hidropirazolo[1,5-a]piridina de platina (II), Px1 e Px2, respetivamente, foram usadas neste estudo. Assim, o objetivo deste estudo foi avaliar a eficácia da PDT com base em Px1 e Px2 (Px-PDT) como uma opção terapêutica conservadora e minimamente invasiva para o EC.Primeiramente, a resposta à PDT foi avaliada em linhas celulares do EC, ECC-1 e RL95-2. Para isso, foram realizados ensaios para avaliar a atividade metabólica, a viabilidade celular e os tipos de morte celular, o ciclo celular, as espécies reativas de oxigénio, o potencial de membrana mitocondrial e a internalização do fotossensibilizador. Numa segunda etapa, foi utilizado um modelo in vitro de células estaminais do cancro (CSC, do inglês Cancer Stem Cells). Através do protocolo de formação de esferas, a resposta das CSC à PDT foi avaliada utilizando os ensaios do Azul Tripano e do Alamar Blue, a área de projeção das esferas, assim como a internalização do fotossensibilizador.Os resultados principais mostraram que ambas as clorinas estudadas são ativas contra as linhas celulares do EC, ECC-1 e RL95-2, mas Px1 apresentou uma maior suscetibilidade aos fotossensibilizadores, apresentando valores de IC50 inferiores a 50 nM em relação à PDT. Px1 apresentou atividade fotodinâmica contra ambas as células tumorais do endométrio, com uma citotoxicidade muito baixa contra essas células na ausência de ativação de luz, o que torna esta clorina num fotossensibilizador para PDT. Além disso, nos ensaios com CSC foi observada uma diminuição da viabilidade, assim como uma diminuição notável da área de projeção de esferas.Em conclusão, ambos os sensibilizadores, Px1 e Px2, apresentaram eficácia como uma opção terapêutica para o EC com base nas novas clorinas, onde o Px1 claramente se destaca. Os resultados obtidos nesta dissertação abrem novos caminhos para a investigação da PDT com base em Px1 no EC não apenas in vitro, mas também in vivo. Outra perspetiva futura é a modulação das clorinas Px para terapêutica dirigida a CSC.
Endometrial cancer (EC) represents about 6% of female cancers, being the most frequent gynaecological malignancy in developed countries. Radical surgery is the primary treatment but in young women or patients with higher surgical risk may not be an option. Moreover, conventional conservative methods have inherent dangers, including inefficiency and the possibility of recurrence. These facts support the need to explore new conservative approaches for EC. Photodynamic therapy (PDT) is a minimally invasive treatment that can be considered for fertility-sparing. Our group recently developed novel very promising chlorins that can be used as photosensitizers in PDT. The 4,5,6,7-tetrahydropyrazolo[1,5-α] pyridine-fused chlorins and Pt (II) 4,5,6,7-tetrahydropyrazolo[1,5-α] pyridine-fused chlorin, Px1 and Px2, respectively, were used in this study. Thus, the aim of this study was to evaluate the effectiveness of Px1 and Px2 based PDT as a treatment option in EC based on new chlorins (Px-PDT) as a conservative and minimally invasive treatment to EC. First, PDT outcome was evaluated in ECC-1 and RL95-2 endometrial cancer cell lines. For this, assays to evaluate metabolic activity, cell viability and types of cell death, cell cycle, reactive oxygen species, mitochondrial membrane potential, and photosensitizer’s internalization were performed. In a second step, an in vitro model of cancer stem cells was used. Through the sphere-forming protocol, CSC response to PDT was evaluated using the trypan blue and Alamar Blue assays, sphere´s projection area, as well as the photosensitizer’s internalization. The main results showed both studied chlorins are active against endometrial cancer cell lines ECC-1 and RL95-2, but Px1 has shown greater PS susceptibility, showing IC50 values below 50 nM regarding photodynamic therapy. Px1 showed PDT activity against both endometrial cancer cells, with a very low cytotoxicity against these cells in the absence of light activation, which makes this chlorin a photosensitizer of choice for PDT. Moreover, in the CSC assays was observed a decrease of viability , as well as a remarkleble decrease of sphere´s projection area. In conclusion, both Px1 and Px2 sensitizers presented effectiveness as a treatment option in EC based on new chlorins (Px-PDT), where Px1 clearly stands out. The results obtainesd in this dissertation open new avenues for the investigation of Px1 based PDT in endometrial cancer not only in vitro but also in vivo. Another future perspective is the modulation of Px chlorins for targeting CSC.
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Lin, Li-Hui, and 林莉惠. "The life experiences among young women with breast cancer receiving adjuvant therapy." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/38639989703962133514.
Full textAbstract:
碩士國立臺北護理健康大學
護理研究所
103
Younger breast cancer women are increasing. The concern issues of these women are different from the middle-aged or older breast women. Younger breast cancer women may face multidimensional impacts such as early menopause, child birth or bearing, marriage, career. However, there are few paper conduct about the subjective experiences of younger breast cancer women in Taiwan. The purpose of this study was to establish the descriptive theory about the subjective living experiences among younger breast cancer women in Taiwan. The study recruited eight breast cancer women from general surgical ward and breast medical center clinic at metropolitan hospitals in north of Taiwan by purposive sampling. The interview manuscripts were analyzed by using constant comparative method. The core category is “keeping in mind and pursuing rebirth-- filial piety for their parents, pampering and having the responsibility of taking care of their families and pets, unfordable work and economic loadings, worrying fertility issues, fear of death and prognosis of treatment.” Antecedent categories are “Finding abnormal breast by one-self” and “uneasy emotion after breast cancer diagnosis” guiding the life process. There were five interactive categories during this process such as “low self-esteem due to the change of appearance after chemotherapy”, “function limitations of the arm after surgery”, “physical and psychological discomfort during receiving adjuvant therapy”, “reproductive issues tangling in mind” and “perceiving social support”. Finally, these women experienced “the modification of their previous life style and returning their works and roles”. Nurses should be pay more attention and sensitive about individual mental and physical care needs of younger breast cancer women. How to share and relieve their concerns issues such as the worries about taking care of their families, birth, career and economics and facing the death would be the challenge for nurses to assist these women returning their life and workplace smoothly. In addition, the study suggested to establish younger breast cancer women support groups is needed in hospitals.
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Cheng, Yi-Jing, and 鄭意靜. "Plasma-activated Medium as Adjuvant Therapy on Lung Cancer Malignant Pleural Effusion." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/ks5tca.
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碩士國立交通大學
機械工程系所
107
Recent studies show that non-thermal atmospheric pressure plasma jet (NTAPPJ) can cause selective apoptosis of tumor cells, which becomes a prospective tendency in cancer treatment. The interdisciplinary research, including plasma engineering and biomedical research, is expected to provide an adjuvant therapy on lung cancer with malignant pleural effusion (MPE). Local lesion of adenocarcinoma cancerometastasis leads to inflammatory exudate infiltrating through pleura into chest. Due to lung under the compression of pleural effusion, patients developed dyspnea, chest pain, and cough. In the past, MPE associated lung adenocarcinoma was regarded as terminal cancer, meaning that there was no radical treatment and that survival rate was low. Traditionally, patients underwent palliative treatment, such as serial thoracentesis, pleural catheter, and pleurodesis. Along with ever-changing technology, new tools, like intrapleural perfusion hyperthermo-chemotherapy and photodynamic therapy (PDT), can inhibit tumor growth and improve survival rate. Nevertheless, they have an impact on surrounding healthy tissue or cause systemic side effects. As a result, another way to cure lung cancer with MPE is needed, and plasma medicine is preferred. Studies have shown that reactive oxygen/nitrogen species (RONS) of NTAPPJ and plasma-activated medium (PAM) induce tumor cells apoptosis and have short half-life. Comparing it with chemotherapy and radiation therapy, plasma medicine is harmless to patients. In the experiment, first and foremost, NTAPPJ system was set up and RPMI medium was treated with NTAPPJ. Then, RONS in PAM were detected. Last but not least, the cells were treated with PAM and their activity, proliferation and migration ability were measured. The preliminary results of the experiment showed that as the plasma application time increases, the concentration of RONS in the PAM increases with increasing plasma treatment time. Further, in the cell viability, proliferation, and migration assay, the lung adenocarcinoma cells were more sensitive to PAM than non-cancer cells. Based on the above results, the application of PAM in the treatment of lung cancer with MPE can be expected soon.
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Chen, Ching-Hung, and 陳慶鴻. "Effects of Adjuvant Endocrine Therapy on Lipid Profiles in Taiwanese Women with Breast Cancer." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/89972962364592821567.
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碩士高雄醫學大學
臨床藥學研究所
98
Background This study intended to evaluate changes in serum lipid profiles in Taiwanese women receiving anastrozole or tamoxifen for early stage breast cancer. The serum lipid profiles included total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB), TC/HDL-C ratio, LDL-C/HDL-C ratio and ApoB/ApoA-1 ratio. Methods It was a prospective cohort study between February 2009 and April 2010. All patients had completed surgery, chemotherapy, and/or radiotherapy and were initially taking 1 mg of anastrozole once daily, or tamoxifen 10 mg twice daily. Patients consenting to participate in this study had blood drawn after overnight fasting and lipid profiles evaluated at baseline, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Results Sixty-eight women were enrolled in the study. The study was analyzed by a Mixed-effects model and adjusted for differences by factors to prevent confounding effects. The factors measured at baseline included age, body-mass-index (BMI), each parameter self and BMI differential value compared with baseline. In TC and LDL-C levels, the anastrozole group increased more than the tamoxifen group, and difference in the change from baseline after 24 weeks was significant (18.5 mg/dL; 22.3 mg/dL respectively). However, the anastrozole group decreased ApoA-1 by 16.3 mg/dL more than the tamoxifen group and showed significant difference in the change from baseline after 12 weeks. TC/HDL-C, LDL-C/HDL-C and ApoB/ApoA-1 ratios increased in the anastrozole group more than the tamoxifen group (0.73; 0.70; 0.12 respectively) and difference in the change from baseline at 24 weeks was significant. Conclusion This study indicates that anastrozole significantly elevates the levels of TC, LDL-C and decreases the level of ApoA-1 in Taiwanese women with breast cancer after 24 weeks of treatments. Anastrozole had a detrimental effect on cardiovascular risk factors. Patients taking anastrozole need to check lipid profiles routinely if they have risks of cardiovascular disease.
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Oliveira, Daniela Isabel Paiva de. "Role of Metformin as co-adjuvant in anticancer therapy targeting Osteosarcoma Cancer Stem Cells." Master's thesis, 2013. http://hdl.handle.net/10316/24656.
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Dissertação de mestrado em Bioquímica, apresentada ao Departamento Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra.Background: Osteosarcoma (OS) is the most common malignant primary bone tumor that appears in childhood and adolescence. It was recently demonstrated that OS possesses a small population with stem-like features, CSCs, which are responsible for the heterogeneity and regenerative ability of tumor cells and are considered responsible for the resistance to conventional therapies, namely chemotherapy and radiotherapy. Metformin (METF) is one of the most prescribed drugs to treat type II diabetes and in the past decade METF gained special attention in cancer treatment because of its anticancer properties. In this study we propose to explore the potential role of METF as an adjuvant of doxorubicin (DOX) to target CSCs from OS, exploring the effects and signaling pathways underlying the anticancer properties of metformin on OS CSCs. Methods: CSCs were isolated from two human OS cell lines MNNG/HOS and MG-63 through the sphere–forming assay and then characterized regarding the expression of stem cell-specific transcription factors by immunofluorescence. The effects of MEFT on cell viability and proliferation was evaluated using the MTT and BrdU assays, respectively, and on sphere formation and self-renewal of CSCs. We also studied the chemosensitizing properties of METF on DOX cytotoxicity in both parental and corresponding CSCs. The metabolic state of cells following exposure to METF was assessed based on [18F]FDG uptake. The phosphorylated form of AMPK, which is the main target of METF and of mTOR were analysed by Western blot. Results: Both human OS cell lines MNNG/HOS and MG-63 contain sphere-forming cell subsets with stem-like properties expressing Oct4 and Nanog pluripotency markers, which are relatively more resistant to DOX than their differentiated counterparts. METF reduced the proliferation rate and viability of both cell types but was preferentially cytotoxic to CSCs relative to parental cells in a dose-dependent manner, and decreased the sphere-forming and self-renewal ability of both CSCs populations. Moreover, METF potentiate the cytotoxic effects of DOX in both cell populations, although the chemosensitizing effect has been more pronounced against CSCs. METF stimulates [18F]FDG uptake in parental differentiated cells but not in CSCs. Exposure to METF induced dose-dependent increase in AMPK activation, with a more pronounced effect in CSCs. Conclusion: MEFT demonstrated a preferential cytotoxicity against CSCs relatively to corresponding parental cells and inhibit the sphere-forming and self-renewal of CSCs. METF induce activation of AMPK and potentiates the cytotoxic effects of DOX mainly in CSCs. Collectively our results suggest that METF combined with DOX may be an effective treatment strategy for targeting CSCs in OS.
Introdução: Osteossarcoma (OS) representa o tumor ósseo primário mais comum aparecendo frequentemente na infância e adolescência. Recentemente foi demonstrada a presença de uma população com características de células estaminais em OS, as células estaminais cancerígenas (CSCs), que são consideradas responsáveis pela heterogeneidade e capacidade regenerativa das células tumorais. Para além disso, são também responsáveis pela resistência a terapias convencionais, como quimioterapia e radioterapia. Metformina (METF) é um dos fármacos mais prescritos no tratamento da diabetes tipo II. Na última década tem ganho especial atenção no tratamento contra o cancro devido às suas propriedades anticancerígenas. Neste estudo foi proposto explorar o papel da METF como adjuvante da doxorrubicina (DOX) tendo como alvo as CSCs de OS, para tal analisámos os efeitos e as vias de sinalização subjacentes às propriedades anticancerígenas da METF nestas CSCs. Métodos: As CSCs foram isoladas a partir das linhas humanas de OS MNNG/HOS e MG-63 pelo método de formação de esferas e posteriormente caracterizadas tendo em conta a expressão de fatores de transcrição específicos de células estaminais, por imunofluorescência. Os efeitos da METF na viabilidade e proliferação celulares foi avaliada através dos ensaios de MTT e BrdU, respetivamente, e na formação de esferas e auto-renovação das CSCs. Também foi analisado o efeito “chemosensitizing” da METF na citotoxicidade da DOX em CSCs assim como em ambas as linhas parentais. O estado metabólico das células após tratamento com METF parentais foi permitido pela análise de captação de [18F]FDG. A forma fosforilada de AMPK, que representa o principal alvo da METF e o mTOR foram analisados por Western Blot. Resultados: Ambas as linhas celulares de OS MNNG/HOS e MG-63 contém uma subpopulação de células com características de células estaminais que expressam marcadores de pluripotência, Oct4 e Nanog. METF, as quais sais são relativamente mais resistentes à DOX do que as células parentais. A METF reduziu a taxa de proliferação e viabilidade em ambos os tipos celulares mas foi preferencialmente citotóxico para as CSCs, sendo este efeito dependente da dose. Também diminuiu a capacidade de formação de esferas e a sua capacidade de auto-renovação. Para além disso, a METF potenciou o efeito citotóxico da DOX em ambas as populações celulares, embora esse efeito tenha sido mais pronunciado nas CSCs. METF aumentou a captação de [18F]FDG nas células parentais diferenciadas mas não nas CSCs. Exposição à METF induziu um aumento dependente da dose na ativação de AMPK, com um efeito mais pronunciado nas CSCs. Conclusão: A METF demonstrou uma citotoxicidade preferencial para as CSCs relativamente às células parentais para além de que diminuiu a formação de esferas e a sua capacidade de autorenovação. METF induziu a ativação de AMPK e potenciou os efeitos citotóxicos de DOX, principalmente nas CSCs. Em conjunto, os nossos resultados sugerem que o tratamento combinado de METF e DOX, pode ser uma abordagem eficaz na eliminação de CSCs no OS.