| 1. |
- Sjövall, Katarina, et al.
(författare)
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To become part of the team-patient experiences of participating in decision-making for a new treatment (proton beam therapy)
- 2024
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Ingår i: Supportive Care in Cancer. - : Springer Nature. - 0941-4355 .- 1433-7339. ; 32:7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to explore patients' experience of participation in the treatment decision of proton beam therapy versus conventional radiotherapy. BACKGROUND: Proton beam therapy (PBT) has become a treatment option for some cancer patients receiving radiotherapy. The decision to give PBT instead of conventional radiotherapy (CRT) needs to be carefully planned together with the patient to ensure that the degree of participation is based on individuals' preferences. There is a knowledge gap of successful approaches to support patients' participation in the decision-making process, which is particularly important when it comes to the situation of having to choose between two treatment options such as PBT and CRT, with similar expected outcomes.METHOD: We conducted a secondary analysis of qualitative data collected from interviews with patients who received PBT for their brain tumor. Transcribed verbatims from interviews with 22 patients were analyzed regarding experiences of participation in the decision-making process leading to PBT.FINDINGS: Participants experienced their participation in the decision-making process to a varying degree, and with individual preferences. Four themes emerged from data: to be a voice that matters, to get control over what will happen, being in the hand of doctors' choice, and feeling selected for treatment.CONCLUSION: A decision for treatment with PBT can be experienced as a privilege but can also cause stress as it might entail practical issues affecting everyday life in a considerable way. For the patient to have confidence in the decision-making process, patients' preferences, expectations, and experiences must be included by the healthcare team. Including the patient in the healthcare team as an equal partner by confirming the person enables and facilitates for patients' voice to be heard and reckoned with. Person-centered care building on a partnership between patients and healthcare professionals should provide the right basis for the decision-making process.
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| 2. |
- Fessé, Per, 1973-
(författare)
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Epidermal Melanocyte Response to Radiotherapy
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cutaneous interfollicular melanocytes protect the skin from UV-radiation (UVR), and their response to UVR is well established. To date, the response activated in melanocytes by repeated genotoxic insults from radiotherapy (RT) has not been explored. Assuming that the molecular pathways involved in the melanocyte response to UVR are similar upon ionizing radiation, the aim of this work was to examine the effects of RT concerning UVR-response proteins and resistance to DNA damage to reveal mechanisms behind hyperpigmentation and depigmentation caused by RT. The results are based on immunostained tissue sections of 530 not sun-exposed skin punch biopsies. These are collected before, during, and after the end of adjuvant RT from the thoracic wall of breast cancer patients and the hip region of prostate cancer patients receiving curative RT. Fractionated RT with daily doses between 0.05 and 2.0 Gy, as well as hypofractionation and accelerated fractionation were investigated. Based on this clinical assay sterilizing the hair follicles, excluding migration of immature melanocytes from the bulge, it was ensured that interfollicular melanocytes are an autonomous self-renewing cell population with cells presenting different degrees of differentiation of which one fourth is immature; the melanocytes divide rarely and are absolute radioresistant to any dose schedule of RT applied, keeping the number of melanocytes intact. Hyperradiosensitivity to dose fractions of 0.05 to 0.3 Gy is observed for DNA double strand breaks (DSBs), differentiation and anti-apoptotic signaling. Proliferation is not stimulated and apoptosis is negligible upon exposure to RT, and also post-treatment. Melanocyte differentiation is maintained during RT, but dedifferentiation occurs after RT ends. The expected activation of the p53/p21 signaling upon RT appears in keratinocytes but is attenuated in melanocytes. A new observation is that melanocytes constitutively express BMI1, further upregulated upon irradiation, indicating that melanocytes have stem cell properties, which suggest that BMI1 prevents apoptosis, terminal differentiation and premature senescence and likely allows dedifferentiation by suppressing the p53/p21-mediated response to genotoxic damage, in addition to the repression of p16 and ARF. Melanocytes exhibit and accumulate a higher amount of DSBs during the RT period compared to keratinocytes, indicating reduced repair capacity of DSBs in melanocytes. Thus, only efficient pro-survival mechanisms can explain the melanocyte radioresistance regarding cell death. The findings in this thesis suggest that melanocytes are protected by activation of the BMI1-NF-kappa/β-CXCL8/CXCR2 pathway, in addition to upregulation of Bcl-2 by melanocyte-specific MITF (microphthalmia-associated transcription factor).
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| 3. |
- Fessé, Per, et al.
(författare)
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Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
- 2022
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 25:10
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Tidskriftsartikel (refereegranskat)abstract
- DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excluded the migration of immature melanocytes from the bulge, and highlighted interfollicular melanocytes as an autonomous self-renewing population. About thirty percent are immature. Surrounding keratinocytes induced and maintained melanocyte differentiation as long as treatment was ongoing. Concomitant with differentiation, melanocytes were protected from apoptosis by transient upregulation of Bcl-2 and CXCR2. CXCR2 upregulation also indicated the instigation of premature senescence, preventing proliferation. The stem cell factor BMI1 was constitutively expressed exclusively in interfollicular melanocytes and further upregulated upon irradiation. BMI1 prevents apoptosis, terminal differentiation, and premature senescence, allowing dedifferentiation post-treatment, by suppressing the p53/p21-and p16-mediated response and upregulating CXCR2 to genotoxic damage. The pre-treatment immature subset of interfollicular melanocytes was restored after the exposure ended.
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| 4. |
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| 5. |
- Fessé, Per, et al.
(författare)
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UV-Radiation Response Proteins Reveal Undifferentiated Cutaneous Interfollicular Melanocytes with Hyperradiosensitivity to Differentiation at 0.05 Gy Radiotherapy Dose Fractions.
- 2019
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Ingår i: Radiation research. - 1938-5404 .- 0033-7587. ; 191:1, s. 93-106
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Tidskriftsartikel (refereegranskat)abstract
- To date, the response activated in melanocytes by repeated genotoxic insults from radiotherapy has not been explored. We hypothesized that the molecular pathways involved in the response of melanocytes to ionizing radiation and ultraviolet radiation (UVR) are similar. Skin punch biopsies, not sun-exposed, were collected from prostate cancer patients before, as well as at 1 and 6.5 weeks after daily doses of 0.05-1.1 Gy. Interfollicular melanocytes were identified by ΔNp63- and eosin-periodic acid Schiff staining. Immunohistochemistry and immunofluorescence were performed to detect molecular markers of the melanocyte lineage. Melanocytes were negative for ΔNp63, and the number remained unchanged over the treatment period. At radiation doses as low as 0.05 Gy, melanocytes express higher protein levels of microphthalmia-associated transcription factor (MITF) and Bcl-2. Subsets of MITF- and Bcl-2-negative melanocytes were identified among interfollicular melanocytes in unexposed skin; the cell number in both subsets was reduced after irradiation in a way that indicates low-dose hyperradiosensitivity. A corresponding increase in MITF- and Bcl-2-positive cells was observed. PAX3 and SOX10 co-localized to some extent with MITF in unexposed skin, more so than after radiotherapy. Low doses of ionizing radiation also intensified c-KIT and DCT staining. Nuclear p53 and p21 were undetectable in melanocytes. Apoptosis and proliferation could not be observed. In conclusion, undifferentiated interfollicular melanocytes were identified, and responded with differentiation in a hypersensitive manner at 0.05 Gy doses. Radioresistance regarding cell death was maintained up to fractionated doses of 1.1 Gy, applied for 7 weeks. The results suggest that the initial steps of melanin synthesis are common to ionizing radiation and UVR, and underline the importance of keratinocyte-melanocyte interaction behind hyperpigmentation and depigmentation to radiotherapy.
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| 6. |
- Turesson, Ingela, et al.
(författare)
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Epidermal Keratinocyte Depletion during Five Weeks of Radiotherapy is Associated with DNA Double-Strand Break Foci, Cell Growth Arrest and Apoptosis: Evidence of Increasing Radioresponsiveness and Lack of Repopulation; The Number of Melanocytes Remains Unchanged
- 2020
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 193:5, s. 481-496
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Tidskriftsartikel (refereegranskat)abstract
- During fractionated radiotherapy, epithelial cell populations are thought to decrease initially, followed by accelerated repopulation to compensate cell loss. However, previous findings in skin with daily 1.1 Gy dose fractions indicate continued and increasing cell depletion. Here we investigated epidermal keratinocyte response with daily 2 Gy fractions as well as accelerated and hypofractionation. Epidermal interfollicular melanocytes were also assessed. Skin-punch biopsies were collected from breast cancer patients before, during and after mastectomy radiotherapy to the thoracic wall with daily 2 Gy fractions for 5 weeks. In addition, 2.4 Gy radiotherapy four times per week and 4 Gy fractions twice per week for 5 weeks, and two times 2 Gy daily for 2.5 weeks, were used. Basal keratinocyte density of the interfollicular epidermis was determined and immunostainings of keratinocytes for DNA double-strand break (DSB) foci, growth arrest, apoptosis and mitosis were quantified. In addition, interfollicular melanocytes were counted. Initially minimal keratinocyte loss was observed followed by pronounced depletion during the second half of treatment and full recovery at 2 weeks post treatment. DSB foci per cell peaked towards the end of treatment. p21-stained cell counts increased during radiotherapy, especially the second half. Apoptotic frequency was low throughout radiotherapy but increased at treatment end. Mitotic cell count was significantly suppressed throughout radiotherapy and did not recover during weekend treatment gaps, but increased more than threefold compared to unexposed skin 2 weeks post-radiotherapy. The number of melanocytes remained constant over the study period. Germinal keratinocyte loss rate increased gradually during daily 2 Gy fractions for 5 weeks, and similarly for hypofractionation. DSB foci number after 2 Gy irradiation revealed an initial radioresistance followed by increasing radiosensitivity. Growth arrest mediated by p21 strongly suggests that cells within or recruited into the cell cycle during treatment are at high risk of loss and do not contribute significantly to repopulation. It is possible that quiescent (G0) cells at treatment completion accounted for the accelerated post-treatment repopulation. Recent knowledge of epidermal tissue regeneration and cell cycle progression during genotoxic and mitogen stress allows for a credible explanation of the current finding. Melanocytes were radioresistant regarding cell depletion. © 2020 by Radiation Research Society. All rights of reproduction in any form reserved.
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