Cutaneous T-Cell Lymphoma (CTCL) Cell Line-Derived Extracellular Vesicles Contain HERV-W-Encoded Fusogenic Syncytin-1

Non peer reviewe

Expression of Syncytin-1 and its receptors ASCT1 and ASCT2 in CTCL cell lines

Cutaneous T-cell lymphomas, CTCL, are a diverse group of non-Hodgking lymphomas that are characterized by malignant T-lymphocytes migrating to the skin. This heterogenous group of diseases may vary from the slowly progressive Mycosis fungoides to the rapidly progressing and aggressive Sezary syndrome. Since the pathomecanism of CTCL is poorly understood, there is no effective treatment for CTCL so far. Human endogenous retroviruses, HERVs, are sequences in our genome, integrated by ancient viruses. Due to insertion into our germline, these gene sequences have become a permanent part of our heredity and are therefore a tempting subject of research. The aim of this study was to investigate the expression of not only the HERV encoded protein syncytin-1 itself, but also its receptors ASCT1 and ASCT2 in different cell-lines of CTCL. For comparison I used ordinary placental cells, where syncytin-1 functions as a part of the normal physiology. Besides, HERV expression has earlier been found to be involved in different pathomechanism of ours, for example the mechanisms behind T-cell leukemia and Multiple sclerosis. In this study, I used cultured CTCL cell lines Mac-1, Mac-2, MyLa and Jurkat. By using immunocytochemistry and western blot I studied the localization and relative amount of expression of the proteins of interest and found the ASCT2 receptor to be expressed in every cell line investigated while ASCT1 and syncytin-1 expression was lower. This study was the first one to show the expression of syncytin-1 receptors in CTCL. Simultaneously the results strengthens the theory of syncytin-1 being involved in the pathomechanism of CTCL and not impossibly of other malignancies as well. Hence, this study offers a new perspective to the development of CTCL treatment.Kutana T-cellslymfom är en varierande grupp av non-Hodgkings T-cellslymfom som karaktäriseras av maligna cellers ansamlande i huden. Denna heterogena grupp av sjukdomar kan variera från den stabila Mycosis fungoides till det sanbbt fortskridande och aggressiva Sezary syndromet. Eftersom mekanismen bakom sjukdomarna är bristfälligt känd, saknar vi effektiv behandling mot dessa lymfom. Endogena retrovirus, ERV, är gensekvenser som forna virus har integrerat i vårt genom. Dessa virus har ursprungligen infekterat våra könsceller och har därmed blivit en permanent del av vårt genetiska arv och ett omtalat ämne inom forskningen. Målet med denna forskning var att undersöka expressionen av ERV kodade proteinet syncytin-1 och dess receptorer i olika slag av kutana T-cellslymfom. Som jämförelse undersökte vi även expressionen i celler från en frisk placenta där syncytin-1 fungerar som en del av vår vanliga fysiologi. Man har dessutom redan tidigare fastställt att ERV kodade protein är involverade i patogenetiska mekanismerna bakom T-cellsleukemi och Multipel skleros. I denna forskning användes odlade CTCL cellinjerna Mac-1, Mac-2, MyLa och Jurkat. Med hjälp av immuncytokemi och western blot undersöktes både lokaliseringen och kvantitativa mängden av proteinerna ifråga. Det framkom att ASCT2 uttrycktes i alla undersökta cellinjerna, medan expression av ASCT1 endas syntes i Jurkat cellinjen. Med westernblot observerades syncytin-1 i alla CTCL cellinjer och även i Jurkat cellerna. Detta var första gången som expressionen av syncytin-1 receptorer påvisades i kutana T-cellslymfom. Detta fynd förstärker teorin om att syncytin-1 deltar i mekanismen bakom dessa sjukdomar och är möjligtvis involverad även i andra maligna sjukdomar. Därmed erbjuder denna forskning en ny synpunkt för utvecklandet av behandlingar mot kutana T-cellslymfo

Mouhijärven murteen konsonantismin historiaa.

Ei julkisesti säilytteillä

Validation of the BODY-Q Chest module in Finnish trans men undergoing chest wall masculinization

Background and objective:The aim of gender affirmation surgery is to ease gender dysphoria. In transgender men, chest wall masculinization is the most common gender affirmation surgery. The BODY-Q Chest module is currently the only instrument developed to measure health-related quality of life (HRQL) in men undergoing chest wall surgery. Linguistic validation and cultural adaption to Finnish were performed previously. The study aims to validate the BODY-Q Chest module in transgender men who have undergone surgical chest wall masculinization.Methods:All transgender patients who underwent chest wall masculinization at Helsinki University Hospital between 2005 and 2018 were invited to the study. The BODY-Q Chest module comprises two scales-chest and nipple. Data were obtained using the BODY-Q Chest module, the 15D questionnaire, and specifically targeted items designed by the authors. The statistical analyses were conducted to exclude selection bias, evaluate validity of the instrument, and compare it to other instruments.Results:Of the 220 patients invited, 123 participated in the survey (response rate 56%). Ceiling effects were observed with 18.9% and 20.5% scoring maximum points. Cronbach's alpha was 0.92 and 0.88 for the chest and nipple scales, respectively. In exploratory factor analysis, both scales loaded to one factor confirming unidimensionality. Correlation with the generic 15D questionnaire was low.Conclusions:The BODY-Q Chest module provides valid scores with sufficient consistency and reliability when measuring HRQL in transgender men undergoing chest wall masculinization. Moreover, it offers specificity that existing or generic instruments cannot provide. Ceiling effect was expected due to the postoperative status of participants.Peer reviewe

Preoperative breast imaging and histopathological findings in chest contouring surgery on transmen

Background: Chest contouring is the most common surgical procedure transmen receive. Only a few articles discuss the importance of preoperative imaging and post- operative histopathological analysis of excised breast tissue. We studied the findings of preoperative breast imaging and the results of postoperative histopathological analysis in a clinical setting.Materials and methods: Data from 220 patients were collected retrospectively from 2005 to 2018. Preoperative imaging modalities and their findings were recorded and classified according to the American College of Radiology Breast Imaging Reporting and Data System. The histopathological findings in breast specimens were categorized based on the World Health Organization Classification of Breast Tumors (5th edition).Results: Preoperative imaging was performed in 133 (60.5%) patients. Patients in the ultrasound-only group were younger (mean age 22.8) than the other groups (mammogram (MGR) 37 years and MGR+US 35.5 years). Preoperative imaging results were normal in 131 (98.5%) patients. Two patients needed further evaluation. Histopathological results were available on 206 (93.6%) patients. The most common histopathological findings were fibrosis (67.5%), atrophy (34.3%), and chronic mastopathy (14.5%). There were no high-risk or malignant findings.Conclusions: The need for further examinations based on routine preoperative imaging was low (1.5%). Therefore, more individualized patient selection for preoperative imaging is justified. There were no high-risk or malignant findings in histopathological analysis, and the occurrence of benign findings was similar to that reported in previous studies. Despite our findings, based on current knowledge, histopathological examination of excised breast tissue can still be recommended. Therefore, future studies are needed to define clear guidelines. (c) 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd.Peer reviewe