La voie de signalisation mTOR (mammalian Target Of Rapamycin) joue un rôle central dans la croissance cellulaire, le métabolisme, et l'homéostasie des lymphocytes T (LT). Lors de la transplantation d'organes, l'administration de rapamycine, un inhibiteur de mTOR (mTORi), bloque l'activation des LT et promeut la polarisation des lymphocytes T CD4 régulateur (Treg). En cancérologie, des mTORi sont utilisés pour leur action inhibitrice sur la prolifération et l'angiogenèse tumorales. Cependant l'immunosuppression via l'induction de Treg nécessaire à la prévention du rejet de greffe pourrait être délétère pour la réponse anti-tumorale. Notre hypothèse est que l'efficacité clinique des mTORi serait également dépendante de la modulation de l'immunité adaptative T induite par ces traitements chez les patients atteints de cancer.Au cours de cette thèse, nous avons abordé cette question immunologique dans une cohorte prospective de patients atteints de cancer rénal métastatique (mRCC) traités par évérolimus. L'analyse du taux de Treg et de la réponse spontanée T CD4 Thl anti-tumorale (anti-télomérase TERT) par Elispot-IFN-y a été effectuée au moment de l'inclusion des patients et tous les deux mois après le début du traitement. Nous avons observé chez la majorité des patients une augmentation du taux de Treg après traitement par évérolimus. Ces Treg expriment Hélios, suggérant un phénotype Treg naturel. La fréquence et la qualité de la réponse Thl anti-TERT sont également augmentées suite au traitement. Nous avons montré que conjointement ces deux paramètres immunologiques corrèlent avec l'efficacité clinique du traitement. Les patients présentant précocement une diminution des Treg associée à une augmentation des Thl anti-TERT ont une meilleure survie par rapport aux patients dont les paramètres immunitaires ne variaient pas, ou variaient dans une même direction (13,2 mois vs 8 et 4 mois). De plus, au moment de la progression la plupart des patients perdaient leur réponse Thl anti-TERT, et cet effet était associé à une augmentation des Treg. Les Treg traités par mTORi in vitro inhibent plus fortement la prolifération de LT allogéniques, par un mécanisme contact dépendant. Par l'utilisation d'anticorps monoclonaux déplétant les LT chez la souris et par l'utilisation de souris DEREG, nous avons montré que la présence de Treg in vivo altère l'efficacité anti-tumorale des mTORi, par un mécanisme impliquant l'inhibition des réponses T CD8 anti-tumorales. En conséquence, l'efficacité des mTORi a pu être augmentée par sa combinaison avec des agents bloquant les Treg. En addition, l'administration de temsirolimus améliore l'efficacité anti-tumorale d'un vaccin thérapeutique, en favorisant la différenciation des LT CD8 anti-tumoraux centraux mémoires (CD62L+CD127+) et précurseurs mémoires (CD127+KLRGl'°) induits par la vaccination.En conclusion, ces études ont montré pour la première fois le rôle de l'immunité T anti-tumorale sur l'efficacité clinique des mTORi et soulignent ainsi l'intérêt potentiel de combiner les mTORi avec des immunothérapies anti-tumorales / The mammalian Target of Rapamycin (mTOR) pathway plays a central role in the regulation of cell growth andmetabolism, and is involved in oncogenesis. Everolimus and temsirolimus are two mTOR inhibitors (mTORi) approvedfor renal and breast carcinoma treatments. However, accumulating evidence highlights a central role for mTOR pathwayin T cell immunity. We showed that 21 out of 23 metastatic renal cell carcinoma patients under everolimus treatmenthad an increase of Tregs atter everolimus treatment. Paradoxically, strong antitumor Th 1 responses were detected andthen greatly decreased at the time of disease progression when high expansion of Tregs occurred. Furthermore, weidentified three immune groups based on the early modulation of both Treg and anti-tumor Thl cells and found thatpatients with {low Tregs plus high anti-tumor Thl cells} showed the best survival. In vitro, mTORi-exposed Tregs highlysuppressed T cell proliferation and Thl-associated cytokines production. We showed in vivo that T cells depletiondifferentially modulated the antitumor efficacy of mTORi. Although anti-mTOR effect was loss in B16-OVA-bearingmice lacking CD8 T cells, CD4 T depletion increased mTORi efficacy. The studies conducted in mice demonstratedthat the presence of Tregs in vivo altered the responses to mTORi via a mechanism involving the inhibition of antitumorCD8 T cell responses. Finally the efficacy of mTORi was improved by combination with Tregs depleting agents andvaccines. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T cell immunity onthe clinical effectiveness of mTQRi and prompt their association with immunotherapies.

This PhD thesis explored the experiences of dependent children and children care-givers facing challenges with their parent s cancer. The aim was to understand children s information experience including their perception of cancer and information culture; information needs, information seeking behaviour, barriers and enablers. The research used a six-stage process. This was informed by an extensive literature review and discussions with cancer specialists, psychologists and researchers from United Kingdom, United States, Australia and Malaysia. This study used a three-cycle, eight-step process of Participative Action Research (PAR) with participation from ten Malay breast cancer patients and their dependent children. Three bilingual (English and Bahasa Malaysia) instruments were developed; 1) An Inquiry to Participate Form to select participants who had dependent children, 2) Three opened-ended questions to obtain children s cancer experience and information needs where drawing was used to encourage children s responses and, 3) A 15-question questionnaire to understand children s experience and information preference. Cancer affected parenting abilities and challenging experiences identified the lack of culturally relevant information and the shift in caregiving responsibilities to dependent children. Children s understanding of cancer was influenced by their experiences and observations, many of which resulted in misconceptions about cancer, its causes, treatment and preventative measures. Children participant s reaction to a health situation triggered their information behaviour. The burden of caregiving and the consequences of a lack of information were greater than anticipated; children had many dimensions of concern and experienced many challenges. This advocated for a more assessable, attractive and sensitive information system. Data synthesis contributed to the development of a Children s Reactive Information Seeking Behaviour An Integrated Model that seeks to explain the relationship between children participants reaction to a health situation and the subsequent processes they undergo to resolve their state of information need.

The thesis discusses the methods of determination of tumor markers and their clinical importance in medical diagnostics. The theoretical part describes clinically important tumor markers and also the chemiluminescent immunoassay methods used for their determination. The practical part of the thesis describes the introduction of new chemiluminescent methods for the determination of tumor markers in routine operation, evaluates its basic analytical parameters and compares it with the existing immunoturbidimetric method. The practical part also presents results of monitoring of cancer patients with various tumors, which is performed by evaluation of the values of tumor markers. Comparison of our method with other methods within the context of System of external quality control is also documented.

MCur / Department of Advanced Nursing Science / See the attached abstract below

In der vorliegenden Arbeit wurde der zelluläre Immunstatus von 17 Patienten mit Erstdiagnose eines soliden gastrointestinalen Tumors vor und nach intravenöser Applikation von drei Zyklen einer konventionellen Polychemotherapie untersucht. Verglichen wurde zu Beginn der Therapie mit einer Kontrollgruppe, bestehend aus 21 nicht onkologisch vorerkrankten Probanden. Zur Messung der individuellen T-Zellvermittelten Immunantwort auf Einzelzellebene wird auf die Methode des IFN-γ-ELISPOT-Assays zurückgegriffen. Die zentrale Frage war, ob die Applikation einer Polychemotherapie einen messbaren Effekt auf die Immunantwort des einzelnen Individuums hat. Zudem sollte untersucht werden, ob generelle Unterschiede zwischen Patienten mit einer unbehandelten Tumorerkrankung und gesunden Probanden bzw. allgemein internistisch erkrankten Patienten zu erkennen sind. In Zusammenschau der Ergebnisse sind trotz überwiegend unveränderter T-Zell-Antwort auf die meisten der eingesetzten Antigene einige statistisch signifikante Unterschiede festzuhalten. So zeigte die Gruppe der Tumorpatienten vor Applikation der Chemotherapie im Vergleich zur Kontrollgruppe eine signifikant erhöhte Spotintensität und einen höheren Stimulationsindex [A] in Bezug auf das Tuberkulose-Antigen CFP-10. Diese Veränderungen waren nach Applikation der Chemotherapie nicht mehr nachzuweisen. Des Weiteren ergaben sich bei den Tumorpatienten vor und nach Chemotherapie signifikante Veränderungen der T-Zell-Antwort bezüglich des Antigens Tetanus-Toxoid. Nach Applikation von 3 Zyklen Chemotherapie kam es zu einer Verminderung des Stimulationsindex [A]. Es wird daher die Vermutung nahe gelegt, dass sich gerade in Bezug auf bakterielle Infektionen die T-Zell-Antwort der Tumorpatienten signifikant ändert. Die klinische Relevanz müsste jedoch anhand gezielter Messung auf spezifische bakterielle Antigene in größer angelegten Studien überprüft werden.

Indiana University-Purdue University Indianapolis (IUPUI) / Greater levels of loneliness have shown consistent associations with poorer mental and physical health; however, the reason for these relationships is unknown. Engagement in poorer health behaviors among individuals with higher levels of loneliness is one potential explanation for this relationship. Self-regulation theory suggests that coping with feelings of loneliness may impair attempts to control health behaviors. Caregivers of cancer patients have been found to have poor health behaviors (e.g., inadequate exercise) and high levels of loneliness. Thus, the aim of the study is to examine whether health behaviors mediate the relationships between loneliness and mental and physical health outcomes among caregivers of cancer patients. Methods: A secondary data analysis was conducted using data from a longitudinal study of cancer patients and their family caregivers who were staying at the American Cancer Society’s Hope Lodge. Participants completed self-report questionnaires measuring levels of loneliness, engagement in health behaviors (i.e., exercise and fruit and vegetable consumption), mental and physical health, and demographic and medical characteristics at three time points over a 4-month period. A bootstrapping macro was used to examine the indirect effect of loneliness on mental and physical health via health behaviors. Results: Contrary to hypotheses, exercise and fruit and vegetable consumption did not mediate the relationships between loneliness and physical and mental health among cancer patients’ caregivers. Additional research is needed to determine whether health behaviors partially account for the relationships between loneliness and health outcomes or whether alternate explanations for these relationships should be considered.

Bakgrund: Cancer drabbar många människor och en vanlig behandlingsmetod är cytostatika. Cytostatika kan administreras intravenöst via en venport och med hjälp av en elastomerisk infusionspump. Idag sker oftast avvecklingen av infusionspump och venportsnål på olika mottagningar. Dock kan många sjukvårdsåtgärder utföras i hemmet av patienterna själva, så kallad egenvård. Motiv: För patienter med cancersjukdom som undergår cytostatikabehandling kan tillvaron till stora delar bestå av provtagningar, cytostatikabehandlingar, läkarmöten, och olika undersökningar. Genom att patienterna självständigt avvecklar infusionspump och venportsnål kan eventuellt deras delaktighet och kontroll öka och en känsla av förbättrad livskvalité möjligen uppnås. Syfte: Denna studie undersökte patienters förmåga att självständigt avveckla infusionspump och venportsnål efter avslutad cytostatikainfusion. Delsyften var att undersöka om det var någon skillnad beroende på vilken typ av miljö avvecklingen utfördes i, samt att belysa patienternas upplevelse av att självständigt utföra momenten. Metod: En observationsstudie med mixad metod genomfördes. Fem patienter genomförde självständig avveckling i två miljöer: på hälsocentral/sjukhus samt i det egna hemmet. Kvantitativ data från observationsprotokoll analyserades genom deskriptiv statistik. Kvalitativ data, deltagarnas kommentarer, analyserades genom tematisk analys. Resultat: Resultatet av den kvantitativa delen visade att det fanns förmåga hos patienterna som deltog i studien att självständigt avveckla infusionspump och venportsnål i hemmet. Vid jämförelse mellan resultaten i de olika miljöerna ses skillnader. Den kvalitativa delen resulterade i 3 olika teman: Förväntansfull tro på sin förmåga, Känsla av något spännande och Känsla av frihet och kontroll. Konklusion: Deltagarna hade förmåga att självständigt avveckla infusionspump och venportsnål i hemmet. De hade även viljan att utföra proceduren och såg flera fördelar med att självständigt utföra avvecklingen i hemmet. / Background: A common treatment method for cancer is chemotherapy administrated intravenously through subcutaneous venous port and elastomeric infusion pump. Today, disconnection of infusion pump and needle is usually done by nurses, however many healthcare tasks can be performed at home by patients themselves, so-called self-care. Motive: Cancer patients undergoing chemotherapy spend a lot of time on receiving treatments and treatment-related activities. By independently disconnecting infusion pump and needle, patients’ participation and quality of life may increase. Other possible benefits are reduced travel costs for patients’ and improved efficiency for healthcare organisations along with the fact that patients would receive their entire chemotherapy treatment. Aim: This study investigated patients’ ability to independently disconnect infusion pump and venous port needle after completing chemotherapy treatment. Sub-aims were to investigate whether there were differences depending on type of environment in which the disconnection took place, as well as to shed light on patients’ experiences of performing the procedure independently. Methods: A mixed method observational study was conducted. Five patients’ performed independent disconnection in two environments: at health center/hospital and in their own homes. Quantitative observation protocols data were analyzed through descriptive statistics. Qualitative data, the participants’ comments, were analyzed through thematic analysis. Result: The quantitative part showed that participants’ had the ability to independently disconnect the infusion pump and venous port needle. When comparing between the two environments, participants’ performed better in their own homes. The qualitative part revealed three themes: Anticipation and belief in one's ability, Feelings of something exciting and Feelings of freedom and control. Conclusion: Participants’ were able to independently disconnect infusion pump and needle at home. They also had the desire to perform the procedure and saw several advantages in independently performing the procedure at home.

This research project examines an array of art prompts and projects that have been used in program-based art making workshops to facilitate creative expression amongst those who have been impacted by a cancer diagnosis. The review of literature emphasizes the value of this research, as the field of healing arts programs/expressive arts workshops in cancer care is varied and sparse. While there is substantial research that indicates art therapy to be a highly valued and accepted clinical intervention used in cancer care, there is little research that focuses on the specific role of art making with cancer patients/survivors and even less research on program-based art making workshops. As an artist and cancer survivor, this research incorporates my lived experiences to inform the cataloging, evaluation, and analysis of five art projects completed and used as inspiration for a program-based art-making workshop. The artworks included are an altered book, a cloth doll, a paper mask, a wooden box, and a Styrofoam head. The five central themes that arose from these five particular projects include that they were fun/engaging, encouraged play/experimentation, increased self-understanding, fostered the need to creatively express unexpressed emotions, and offered a sense of pride/accomplishment. This preliminary research project suggests that a broader investigation is needed in order to gather a deeper understanding of the impact of program-based expressive arts workshops as a healing modality with this patient population.

Objective: Recent evidence suggests that illness perceptions in paediatric patients and their parents may differ, with parents holding more negative views compared to their children. Little is known about illness perceptions of very young patients and their parents. This study investigates illness perceptions in paediatric cancer patients aged 4–18 years and their parents in acute treatment or follow‐up care, distinguishing patients by age (4–11, 12–18) and stage of medical treatment. - Methods: N = 45 patient–parent dyads in acute treatment and n = 95 dyads in follow‐up care were examined. Parents and older children aged 12–18 years completed the Illness Perception Questionnaire—Revised (IPQ‐R) and younger children aged 4–11 years were examined using an age‐adapted hand puppet interview containing the IPQ‐R questions. Difference scores of illness perceptions (symptoms, timeline‐acute/chronic, timeline‐cyclical, personal control, illness coherence, consequences, emotional representations) between children and parents were tested for significance using Wilcoxon signed‐rank tests. - Results: Overall, parents perceived more symptoms associated with their child's illness/treatment than the children themselves. In acute treatment, younger children indicated more negative and older children more positive views regarding chronicity than parents. Younger children held less negative views on consequences, and all children reported less negative emotional representations than parents. In follow‐up care, all children held less negative views on consequences and emotional representations. Older children reported less negative views on chronicity, cyclicity and illness coherence. - Conclusion: Differences in illness perceptions of paediatric patients and their parents should be considered during and after treatment/medication and psychosocial care to support illness coping in person‐ and family‐centred interventions.

This research was aimed at listening to the care stories of people living with cancer in remission. The participants spoke about relationships with their families, medical professionals and their spirituality, thereby giving a voice to personal experiences of cancer as part of family life. Postmodern social construction discourse guided the explaining of how cancer invades and affects people's Jives and relationships. This participatory action research was situated in a contextual practical theology. Narrative conversations with the participants spoke about experiences of both care and communication by medical professionals, their struggles in communicating with their partners and families, their spiritual search and longing for pastoral care to sustain and guide them. / Practical Theology / M.Th. (Pastoral Therapy)