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- Lindström, Annika, 1953-
(författare)
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Prognostic factors for squamous cell cervical cancer : tumor markers, hormones, smoking, and S-phase fraction
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cervical cancer is the second most common malignancy in women worldwide and one of the leading causes of cancer mortality globally. In patients with invasive cervical cancer prognostic factors are of value for the choice of treatment, monitoring of treatment and follow-up. The most important clinical prognostic factors are stage, tumor volume, parametrial infiltration, vascular invasion, lymph node metastases, and distant metastases. An improved estimation of the prognosis of cervical cancer is desirable, especially in early cancer stages.The aim of this research was to study possible associations between tumor markers, female sex steroids, smoking, S-phase fraction (SPF), and prognosis in invasive squamous cell cervical cancer (SCC). The study comprised 190 patients with SCC, stages IB-IV, admitted to the Department of Gynecologic Oncology at Norrland University Hospital in Umeå between September 1984 and October1990. Ten year mortality was estimated.In study I, of a total of 103 patients, it was found that increased tumor growth, measured by the DNA SPF, was associated with elevated serum progesterone and smoking in the premenopasual patients and with aneuploidy in the whole group.In study II, comprising 128 patients, survival length related to hormone levels and SPF was evaluated in women who died of cervical cancer. In both pre- and postmenopausal women, who died of cervical cancer, SPF at or above 12% was correlated with reduced survival. There was significant positive correlation between a low serum estradiol/progesterone ratio and short survival in those premenopausal women who died of cancer (p=0.02).In study III, ten-year follow-up results in 128 women were compared with the expression of ten relevant tumor markers, assessed by immunohistochemistry. The overall ten-year survival rate in patients with low COX-2 and high CD4+ expression was 76%, versus 53% in the remaining women. The survival rate with absent p53 and high COX-2 expression in the tumors was 42%, versus 71%, while the corresponding figure for the combination of high COX-2 intensity and expression of c-myc was 27%, versus 62%. None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did.Study IV addressed possible associations between selected tumor markers and cofactors in SCC. Ten tumor markers were examined in 128 patients. Smoking habits and previous oral contraceptive use were recorded. Serum estradiol and progesterone levels were evaluated in 80 women. Highly significant associations were found between strong c-myc staining and increased progesterone, low EGFR staining and high serum estradiol, and absence of p53 staining and smoking. There was an association between absence of p53 and high serum progesterone.In study V, LRIG1 expression was studied in 128 patients and was compared with expression of nine other tumor markers, smoking history, hormone levels, and prognosis. LRIG1 appears to be a significant prognostic predictor in early stage SCC, independent of the other tumor markers that were studied. Diminished expression in advanced cancer stages and the inverse correlation to serum progesterone and smoking indicate that LRIG1 is a tumor suppressor in squamous cell cervical cancer.Conclusion: The results of these studies support a role of progesterone as a promoter of cervical cancer and indicate that smoking is associated with tumor progression. A combination of tumor markers might be of help in prognostic prediction. LRIG1 acts as a tumor suppressor. These findings might contribute towards greater understanding of prognostic prediction of squamous cell cervical cancer.
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| 2. |
- Randell, Eva, 1960-
(författare)
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Adolescent boys’ health : managing emotions, masculinities and subjective social status
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The health of adolescent boys is complex and surprisingly little is known about how adolescent boys perceive, conceptualise and experience their health. Thus, the overall aim of this thesis was to explore adolescent boys’ perceptions and experiences of health, emotions, masculinity and subjective social status (SSS).This thesis consists of a qualitative, a quantitative and a mixed methods study. The qualitative study aimed to explore how adolescent boys understand the concept of health and what they find important for its achievement. Furthermore, the adolescent boys’ views of masculinity, emotion management and their potential effects on wellbeing were explored. For this purpose, individual interviews were conducted with 33 adolescent boys aged 16-17 years. The quantitative study aimed to investigate the associations between pride, shame and health in adolescence. Data were collected through a cross-sectional postal survey with 705 adolescents. The purpose of the mixed methods study was to investigate associations between SSS in school, socioeconomic status (SES) and self-rated health (SRH), and to explore the concept of SSS in school. Cross-sectional data were combined with interview data in which the meaning of SSS was further explored. Individual interviews with 35 adolescents aged 17-18 years were conducted.In the qualitative study, data were analysed using Grounded Theory. In the quantitative study, statistical analyses (e.g., chi-square test and uni- and multivariable logistic regression analyses) were performed. In the mixed method study, a combination of statistical analyses and thematic network analysis was applied.The results showed that there was a complexity in how the adolescent boys viewed, experienced, dealt with and valued health. On a conceptual level, they perceived health as holistic but when dealing with difficult emotions, they were prone to separate the body from the mind. Thus, the adolescent boys experienced a difference between health as a concept and health as an experience (paper I). Concerning emotional orientation in masculinity, two main categories of masculine conceptions were identified: a gender-normative masculinity and a non-gender-normative masculinity (paper II). Gender-normative masculinity comprised two seemingly opposite emotional masculinity orientations, one towards toughness and the other towards sensitivity, both of which were highly influenced by contextual and situational group norms and demands, despite that their expressions are in contrast to each other. Non-gender-normative masculinity included an orientation towards sincerity, emphasising the personal values of the boys. Emotions were expressed more independently of peer group norms. The findings suggest that different masculinities and the expression of emotions are intricately intertwined and that managing emotions is vital for wellbeing. The present findings also showed that both shame and pride were significantly associated with SRH, and furthermore, that there seems to be a protective effect of experiencing pride for health (paper III). The results also demonstrated that SSS is strongly related to SRH, and high SRH is related to high SSS, and further that the positioning was done in a gendered space (paper IV).Results from all studies suggest that the emotional and relational aspects, as well as perceived SSS, were strongly related to SRH. Positive emotions, trustful relationships and having a sense of belonging were important factors for health and pride was an important emotion protecting health. Physical health, on the other hand, had a more subordinated value, but the body was experienced as an important tool to achieve health. Even though health was mainly perceived in a holistic manner by the boys, there were boys who were prone to dichotomise the health experience into a mind-body dualism when having to deal with difficult emotions.In conclusion, this thesis demonstrates that young, masculine health is largely experienced through emotions and relationships between individuals and their contexts affected by gendered practices. Health is to feel and function well in mind and body and to have trusting relationships. The results support theories on health as a social construction of interconnected processes. Having confidence in self-esteem, access to trustful relationships and the courage to resist traditional masculine norms while still reinforcing and maintaining social status are all conducive to good health. Researchers as well as professionals need to consider the complexity of adolescent boys’ health in which norms, values, relationships and gender form its social determinants. Those working with young boys should encourage them to integrate physical, social and emotional aspects of health into an interconnected and holistic experience.
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| 3. |
- Sellin, Mikael E, 1979-
(författare)
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Cytoskeletal filament systems : assembly, regulation, and interplay in mammalian cells
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cell represents the basic unit of structure and function for all life. The interior of a eukaryotic cell is organized by an extensive array of protein filaments – collectively referred to as the cytoskeleton. These filaments serve diverse essential functions, e.g. to provide mechanical resilience, facilitate intracellular transport, and enable cell polarization, locomotion and division. Here I have explored the mechanisms that regulate synthesis and assembly of two cytoskeletal filament systems – microtubules and septins – and how these interact in human cells. The present thesis is based on three principal discoveries. Firstly, we have found that the microtubule-destabilizing protein Op18/Stathmin also regulates synthesis of tubulin heterodimers, which are the building blocks for microtubules. Secondly, we have unraveled the general rules that govern assembly of mammalian septins into native polymerization-competent heterooligomers. Finally, our combined results point to a non-reciprocal interplay whereby interphase microtubules support a disc-like arrangement of septin filaments, which delineate static plasma membrane regions. I here discuss the physiological significance and implications of these findings.
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