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Tumor antigen-specific redirection of cytotoxic T cells (CTLs) or natural killer (NK) cells including chimeric antigen receptor (CAR-) and T cell receptor (TCR-) cell therapy is currently being evaluated in different tumor entities including melanoma. Expression of melanoma-specific antigen recognized by the respective CAR or TCR directly or presented by HLA molecules is an indispensable prerequisite for this innovative therapy. In this study, we investigated in 168 FFPE tumor specimens of patients with stage I-IV melanoma the protein expression of HER2, TRP2, ABCB5, gp100, p53, and GD2 by immunohistochemistry (IHC). These results were correlated with clinical parameters. Membrane expression of HER2 and GD2 was also investigated in ten melanoma cell lines by flow cytometry for which corresponding tumors were analyzed by IHC. Our results demonstrated that gp100 was the most frequently overexpressed protein (61%), followed by TRP2 (50%), GD2 (38%), p53 (37%), ABCB5 (17%), and HER2 (3%). TRP2 expression was higher in primary tumors compared to metastases (p = 0.005). Accordingly, TRP2 and ABCB5 expression was significantly associated with lower tumor thickness of the primary (p = 0.013 and p = 0.025). There was no association between protein expression levels and survival in advanced melanoma patients. Flow cytometric analysis revealed abundant surface expression of GD2 and HER2 in all melanoma cell lines. The discordant HER2 expression in situ and in vitro suggests a tissue culture associated induction. In summary, our data support the use of gp100 and GD2 as a potential target for developing engineered TCR- or CAR-cell therapies, respectively, against melanoma.
Das prämenstruelle Syndrom (PMS) ist ein häufiges Krankheitsbild, das bei 20–30 % der gebärfähigen Frauen auftritt. Es wird durch zyklusabhängige psychische und somatische Symptome definiert.
Die prämenstruelle dysphorische Störung (PMDS) ist eine schwere Form des PMS mit vor allem psychischen Auffälligkeiten, die bei 2–8 % der gebärfähigen Frauen vorkommt. Die Ätiologie von PMS und PMDS bleibt unklar. Eine PMDS geht oft mit anderen psychischen Erkrankungen einher.
Die Symptome treten in der zweiten Zyklushälfte auf und lassen mit Beginn der Periode nach. Zur Diagnosestellung hilft die Führung eines Zykluskalenders.
Ein gesunder Lebensstil (Sport, ausgeglichene Ernährung etc.) stellt die Basis für alle Therapieoptionen dar. Zahlreiche Studien konnten die Effektivität der Behandlung mit Antidepressiva (aus der SSRI- oder SNRI-Gruppe) sowie Ovulationshemmern darlegen.
Beide Medikamentengruppen werden in Deutschland im „off label use“ zur Behandlung von PMS/PMDS-Beschwerden angewendet. Für die Therapieempfehlung sind die Grunderkrankungen der Patientin zu berücksichtigen.
Der rätselhafte Fall
(2022)
Purpose: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. Despite the existence of a detailed, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE), it remains unclear to what extent healthcare providers adhere to this guideline. Our aim is to evaluate the gynaecological medical care provided in women with PCOS, particularly in terms of mental health, from the patients' perspective.
Methods: For this cross-sectional online cohort study in women with PCOS, we designed a standardized, non-validated questionnaire covering aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic non-communicable diseases.
Results: Among 1879 participants, various mental health aspects were reported: body image (n = 1879), eating patterns/habits (n = 1878), and emotional well-being (n = 1874). Although nearly all women (99.7%) reported complaints on at least one session of mental health, consultation rates were low (body image 9.7%, eating patterns/habits 16.6%, emotional well-being 4.4%). Mean satisfaction with counselling on the different domains varied from moderate to fairly satisfying, with scores of 56.0 points (SD 31.7), 53.5 points (SD 32.0), and 63.7 points (SD 30.2), respectively. More complaints were associated with lower satisfaction. The overall satisfaction with the management provided by the healthcare practitioner (HCP) was low, averaging 36.5 points (SD 29.7). Consequently, most women wished for more counselling (58.9%).
Conclusion: Women affected by PCOS are not properly managed according to ESHRE guideline in regard to mental health issues. Overall consultation rates and corresponding satisfaction with management were poor, highlighting the need for significant improvements in healthcare provision.