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- Boraka, Öykü
(författare)
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Breast Cancer Prevention – lifestyle modifications or targeted interventions?
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is now the most frequently diagnosed cancer in the world. Breast cancer prevention has gained increasing attention due to increasing breast cancer incidence rates in the West and can be actualized through lifestyle modifications or targeted interventions. Mammographic breast density (MBD) is a well-established independent breast cancer risk factor that is not well-understood on a molecular level. The aim of this thesis work was to offer further insight to breast cancer prevention with a special focus on mammographic breast density.We first investigated physical activity as a lifestyle modification in studies I and II. In study I, we found that physical activity of at least 1 hour walking per day was associated with an overall breast cancer risk reduction by 23%. The risk reduction was predominantly observed for women who exercised during or after menopause and women who had lower-middle and upper-middle values of body composition. Study II examined physical activity in relation to MBD, mammographic appearances, and mode of breast cancer detection in breast cancer patients; we found no association for any of the mammographic features.We also investigated FGF/FGFR1 system and tamoxifen responses as potential targets for intervention in studies III and IV. In study III, we showed that FGFR1 expression was upregulated in almost 60% of tumor tissues versus tumor-adjacent tissues from the same patients. We further showed that FGFR1 expression was associated with less favorable tumor characteristics. We noted associations between FGF ligand expression and MBD. Study IV showed that tamoxifen inhibited the proliferation, disrupted the cell cycle progression, and inhibited the ECM adhesion capacity of healthy breast epithelial cells.In conclusion, we offer further evidence on physical activity as a breast cancer preventive measure with details on life stage and body composition. We studied mammographic appearances and mode of breast cancer detection in relation to physical activity for the first time and also proposed novel findings supporting a role for the FGF/FGFR1 system in MBD-driven breast carcinogenesis. Mechanistic insight for tamoxifen as a breast cancer preventive drug was also elucidated.
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| 3. |
- Heyward, Clare, et al.
(författare)
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A free movement passport for the territorially dispossessed
- 2016
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Ingår i: Climate justice in a non-ideal world. - Oxford : Oxford University Press. - 9780198744047 - 9780191804038 ; , s. 208-226
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Clare Heyward and Jörgen Ödalen focus on the need for institutional reform to address climate-related injustice for a particular group of victims. They are concerned with the potential lacuna in international law concerning those citizens of states whose entire territories could be submerged by rising sea levels. Heyward and Ödalen refer to these as the the ‘territorially dispossessed’ and argue that they should be provided with a ‘Passport for the Territorially Dispossessed’ which gives its holder a right to choose their new nationality. They compare their proposal with competing ‘quota’ schemes and argue that the PTD is less unjust because its principle of free choice allows the territorially dispossessed to retain a larger measure of control over their destiny.
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| 4. |
- Mathus-Vliegen, Elisabeth, et al.
(författare)
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Weight loss with or without intragastric balloon causes divergent effects on ghrelin cell expression
- 2021
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Ingår i: Obesity Science & Practice. - : Wiley-Blackwell Publishing Inc.. - 2055-2238. ; 7:2, s. 199-207
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The mechanism of action of intragastric balloons in the treatment of obesity is not fully understood. One of the hypotheses is that balloons might have an effect on the fundus, the area of ghrelin production. Methods: Participants were randomized to a 13-week period of sham or balloon treatment followed by a 13-week period of balloon therapy in everyone. Blood samples for ghrelin levels were taken in the fasting state and after a breakfast at the start, after 13 and 26 weeks. Biopsies for ghrelin cell immunohistochemistry were taken from the fundus at endoscopy. Results: Seven participants entered the balloon-balloon (BB) group and 11 the sham-balloon (SB) group. Despite a considerable weight loss, a median -17.9 kg (interquartile ranges -23.8 to -0.5) in the BB group and -18.3 kg (-22.7 to -14.7) in the SB group, fasting ghrelin and meal-induced ghrelin response did not change. In the SB group, the number of ghrelin cells increased significantly (p 0.001) from 110.6 (83.6-118.9) to 160.2 (128.5-223.0) while on sham treatment and returned to initial levels, 116.3 (91.7-146.9) (p 0.001), when they received their first balloon. No significant changes in ghrelin cell numbers were observed in the BB group. Conclusion: In participants without a balloon, weight loss induced an increase in ghrelin cell numbers in the fundus, which was annulled by the subsequent placement of a balloon. The effect of a balloon might be explained by effects on ghrelin cell numbers or ghrelin cell activity.
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| 5. |
- Satapathy, Shakti Ranjan, et al.
(författare)
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The tumor promoter cysteinyl leukotriene receptor 1 regulates PD-L1 expression in colon cancer cells via the Wnt/β-catenin signaling axis
- 2023
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Ingår i: Cell Communication and Signaling. - 1478-811X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy targeting programmed death-ligand 1 (PD-L1) or PD-1 in solid tumors has been shown to be clinically beneficial. However, in colorectal cancer (CRC), only a subset of patients benefit from PD-1/PD-L1 treatment. Previously, we showed that high cysteinyl leukotriene receptor 1 (CysLT1R) levels are associated with poor prognosis in CRC patients. Recently, we have revealed the role of the tumor promoter CysLT1R in drug resistance and stemness in colon cancer (CC) cells. Here, we show the role of the CysLT1R/Wnt/β-catenin signaling axis in the regulation of PD-L1 using both in vitro and in vivo preclinical model systems. Interestingly, we found that both endogenous and IFNγ-induced PD-L1 expression in CC cells is mediated through upregulation of CysLT1R, which enhances Wnt/β-catenin signaling. Therapeutic targeting of CysLT1R with its antagonist montelukast (Mo), as well as CRISPR/Cas9-mediated or doxycycline-inducible functional absence of CysLT1R, negatively regulated PD-L1 expression in CC cells. Interestingly, an anti-PD-L1 neutralizing antibody exhibited stronger effects together with the CysLT1R antagonist in cells (Apcmut or CTNNB1mut) with either endogenous or IFNγ-induced PD-L1 expression. Additionally, mice treated with Mo showed depletion of PD-L1 mRNA and protein. Moreover, in CC cells with combined treatment of a Wnt inhibitor and an anti-PD-L1 antibody was effective only in β-catenin-dependent (APCmut) context. Finally, analysis of public dataset showed positive correlations between the PD-L1 and CysLT1R mRNA levels. These results elucidate a previously underappreciated CysLT1R/Wnt/β-catenin signaling pathway in the context of PD-L1 inhibition in CC, which might be considered for improving the efficacy of anti-PD-L1 therapy in CC patients.
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