Skip directly to content

Coming theses from other universities

  • The art of ageing well - a salutogenic perspective on physical activity for older adults Author: Helena Ericson Link: Publication date: 2022-05-25 08:38
  • Human iPSC-based models of theCNS: attaining cellular biofidelitythrough conventional and advancedculture systems Author: Dimitrios Voulgaris Link: Publication date: 2022-05-24 14:41

    Brain development is a highly orchestrated process that entails changes in microenvironmental cues and growth factor gradients, which set the tempo for proper development of the rudimentary structures of the brain and the generation of neurons,astrocytes, and oligodendrocytes. Another intricate feature of the brain is the bloodbrain barrier (BBB). The BBB consists of specialized endothelial cells that form asemipermeable barrier between the blood and the brain; hence, the BBB plays animportant part in protecting the brain from blood-borne pathogens. In vitro modeling is inherently limiting, an artificial microenvironment that is usually not in tunewith in vivo conditions. Thus, understanding these cues and growth factor conditions is pivotal for proper in vitro modeling and achieving cell biomimicry in vitro.Stem cell differentiation is highly amenable to growth factors and microenvironmental cues that can alter the expression of proteins. Advanced in vitro culturingconsiders microenvironmental cues and applies a more holistic aspect to in vitromodeling. This thesis evaluates microenvironmental cues in neural stem cell generation and astrocyte generation by employing induced pluripotent stem cells (iPSC).This thesis introduces a new protocol for generating human iPSC-derived astrocytesin under 28 days. By creating an astrocytogenic milieu, neural stem cells give riseto star-shaped astrocytes that encompass many traits previously unmet in iPSC-derived astrocytes, namely, ICAM-1 expression under inflammatory stimulation, glutathione synthesis and secretion. A follow-up study in this thesis presents a proteomic analysis between primary fetal astrocytes and iPSC-derived astrocytes. Microphysiological systems impart a more appropriate culturing microenvironment andinfluence cell fate and functionality. Another study of this thesis focuses on thedifferences between conventional and microphysiological culture systems in iPSCreprogramming and the generation of neural stem cells. Lastly, in vitro modeling ofthe blood-brain barrier (BBB) is also investigated. Specifically, 1) a human iPSCBBB-like model is used to evaluate the permeability of a drug delivery system basedon nanostructured lipid carriers and 2) a vessel-like structure with a 3D gliomamodel.

  • Complementary and alternative medicine in cancer : from utilization to a randomized controlled trial Author: Kathrin Wode Link: Publication date: 2022-05-24 07:00

    Background: Complementary and alternative medicine (CAM) are non-conventional health care approaches used in parallel with or instead of conventional medicine. Little is known about Swedish patients’ patterns of complementary CAM use in the context of cancer. Patient-provider communication concerning CAM is crucial and research about communication in situations when patients decline recommended cancer treatment and consider CAM as an alternative is scarce. One commonly used CAM approach is an herbal medicinal product from mistletoe. An open-label trial on mistletoe extract for patients with advanced pancreatic cancer reported promising results on overall survival and quality of life. Due to limited treatment options for this group of patients, this approach needs to be investigated further. 

    Aim: The overall aim of this thesis is to explore CAM use from patients’ and physicians’ perspectives and to design a placebo-controlled randomized clinical trial to assess mistletoe extract as a complement to standard treatment in patients with advanced pancreatic cancer. 

    Methods: A cross-sectional design with quantitative and qualitative mixed methods was used in Study I including 755 patients with solid tumors. In Study II a qualitative design with face-to-face interviews with seven patients with cancer and ten physicians from cancer care was used. In Study III, a study protocol for a multicenter, parallel group, double-blind, randomized, placebo-controlled clinical trial (RCT) was developed. Mixed methods were used by two nested ancillary studies on sub-sets of participants with a translational and a qualitative design respectively. Patients with advanced pancreatic cancer (n=290) were included; mistletoe extract/placebo was added to treatment of choice for the duration of nine months. The trial is currently being conducted. 

    Results: One of four patients with solid tumors used CAM parallel with conventional treatment. Main reasons motivations were the hope for improvement of physical, general, and emotional wellbeing and the body’s ability to fight cancer. Satisfaction with CAM usage was generally high; reported adverse effects few and mild. One third had discussed their CAM use with cancer care providers. More than half of the patients thought that cancer care providers should be able to discuss and/or consider use of CAM modalities in cancer care. 

    Patients declining conventional cancer treatment while using CAM had a variety of reasons for their choices: many of them valued CAM for a broader perspective on health and illness in the context of mind, body and spirit. The wish to take an active stance in relation to treatment decisions and previous negative experiences from conventional care were also cited as motives. Some patients felt a lack of respect for their choices and indicated lack of knowledge and interest on their physicians’ part. Some physicians felt a need for better expertise in CAM while others did not. Patients’ choice to decline cancer treatment was an ethical dilemma to most of the interviewed physicians. Even though communication in these situations tended to push some patients and physicians to take an extreme position, both parties wished for an open dialogue with mutual trust and understanding.

    The study protocol of Study III was designed and published according to the Standard Protocol Items for Clinical Trials (SPIRIT) guidelines. The trial started inclusion in 2016 and has been running at nine participating oncological departments. Inclusion was completed in December 2021 and expected end-of-study is September 2022. Thirty-one interviews have been conducted within the ancillary qualitative study and 100 patients were included in the biomarker study.

    Conclusions: Many patients with cancer use CAM, mainly as a complement to conventional treatment to improve wellbeing. Most have realistic expectations, express high satisfaction and awareness of side effects. In rare cases, patients decline conventional cancer treatment and use CAM as an alternative for complex reasons that are worthwhile to explore in concrete situations. Patients generally wish to stay in contact with cancer care but demand interest in and respect for their choices. The majority of CAM-using patients perceive a lack of knowledge about CAM among cancer care providers and do often not reveal their CAM use; however, patients want providers to be knowledgeable and able to give advice. Shared decision-making appears extra difficult in the clinically demanding situations when patients’ and physicians’ views on treatment choices profoundly diverge. Knowledge about CAM and competency in giving nuanced advice to interested patients seem crucial for an initiated patient-provider dialogue for safety reasons, patient satisfaction and mutual trust. 

    Both design and conduct of the RCT are an example of research filling an identified gap of knowledge and will provide cancer care with much-needed information. The design and conduct of this trial as well as its future results may serve as a model for CAM knowledge capacity building. 

    Evidence-based medicine is the practice of integrating individual clinical expertise and patient values with the best available external clinical evidence from systematic research. This thesis pays attention to patients’ values, builds professional competency and experience within CAM and acknowledges and contributes to systematic research.