Publications by authors named "Doris Mayr"

Introduction: Homologous recombination deficiency (HRD) is a key biomarker in the management of high-grade serous ovarian cancer (HGSOC), guiding treatment decisions, particularly regarding the use of poly(ADP-ribose) polymerase inhibitors (PARPi). As multiple HRD assays are available, each with distinct methodologies and cutoff values, the interpretation and clinical application of HRD testing remain complex. This intergroup statement, endorsed by the German Ovarian Cancer Commission, NOGGO, AGO Austria, and AGO Swiss, aims to provide guidance on the indications, appropriate use, and limitations of HRD testing in ovarian cancer.

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Childhood-onset mitochondrial disorders are rare genetic diseases that often manifest with neurological impairment due to altered mitochondrial structure or function. To date, pathogenic variants in 373 genes across the nuclear and mitochondrial genomes have been linked to mitochondrial disease, but the ensuing genetic and clinical complexity of these disorders poses considerable challenges to their diagnosis and management. Nevertheless, despite the current lack of curative treatment, recent advances in next generation sequencing and -omics technologies have laid the foundation for precision mitochondrial medicine through enhanced diagnostic accuracy and greater insight into pathomechanisms.

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Melanoma arising from pigment-producing melanocytes is the deadliest form of skin cancer. Extensive ultraviolet light exposure is a major cause of melanoma and individuals with low levels of melanin are at particular risk. Humans carrying gain-of-function polymorphisms in the melanosomal/endolysosomal two-pore cation channel TPC2 present with hypopigmentation, blond hair, and albinism.

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Article Synopsis
  • - Two siblings showed high levels of galactose-related substances in newborn tests, but standard enzyme tests for galactose metabolism came back normal.
  • - Whole-exome sequencing revealed a significant genetic variant in the PPA1 gene, affecting the enzyme’s function and stability, leading to reduced enzyme activity in patient skin cells.
  • - The findings suggest a potential mild deficiency in PPA1 that could explain abnormal galactose metabolism; this may represent a newly recognized metabolic disorder that could be detected in broader newborn screenings.
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Background: Histopathological examination is still the backbone for the diagnosis and treatment decision making in endometrial carcinoma (EC). The binary classification of EC into type 1 (mostly endometrioid) and type 2 (mostly serous), although still helpful, showed overlapping clinical, morphological and molecular features and was not very prognostic discriminatory for all subtypes of EC.

Methods: Analysing the most recent studies dealing with the molecular classification of EC and the recommendations of the German S3-guidelines for EC.

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The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020.

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Article Synopsis
  • - The S3-guideline for endometrial cancer, initially released in April 2018, underwent a comprehensive review and update from April 2020 to January 2022, as requested by German Cancer Aid and coordinated by prominent gynecological and oncology organizations in Germany.
  • - The update focused on integrating new evidence and refining recommendations to enhance treatment approaches, emphasizing personalized therapies to minimize unnecessary radical surgeries and non-beneficial adjuvant treatments for low-risk patients.
  • - The revised guideline aims to optimize care for high-risk patients by clarifying the roles of radical surgery and additional treatments, ultimately improving survival rates and quality of life, while serving as a foundation for certified gynecological cancer centers.
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Background: Breast implant-associated squamous cell carcinoma (BIA-SCC) is being discussed as a distinct malignant tumour entity originating from the implant capsule. The FDA and the ASPS published a safety communication on BIA-SCC in 2022, with a first case report of BIA-SCC having been published in the 1990s. This manuscript summarises the current scientific data on this rare tumour entity.

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Introduction: The association between human papilloma virus (HPV) and the pathogenesis of prostate cancer (PCa) is still controversial. Existing studies often lack information about clinical risk factors, are limited by their retrospective design or only use a single detection method for HPV.

Material And Methods: A total of 140 patients undergoing radical prostatectomy (RP) for PCa at the Department of Urology, Ludwig Maximilian University of Munich, Germany, were prospectively enrolled.

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Primary sclerosing cholangitis (PSC) represents a chronic liver disease characterized by poor prognosis and lacking causal treatment options. Yes-associated protein (YAP) functions as a critical mediator of fibrogenesis; however, its therapeutic potential in chronic biliary diseases such as PSC remains unestablished. The objective of this study is to elucidate the possible significance of YAP inhibition in biliary fibrosis by examining the pathophysiology of hepatic stellate cells (HSC) and biliary epithelial cells (BEC).

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Background: The therapy concepts that target several members of krüppel like factor (KLF) family have been achieved in breast cancer (BC). However, the role of KLF11 in BC remains unclear. This study explored the prognostic significance of KLF11 in BC patients and investigated its functional roles in this malignancy.

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Introduction: The enzymes Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) und 3 (RIPK3) as well as the protein Mixed lineage kinase domain like pseudokinase (pMLKL) play a role in the signaling cascade of necroptosis. This is a form of programmed cell death which is caspase-independent. High-risk human papilloma virus infection can inhibit necroptosis.

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Article Synopsis
  • The study investigates the role of the nuclear co-repressor NCOR2 in the G-protein-coupled estrogen receptor (GPER) signaling and its potential impact on ovarian cancer survival rates.
  • Researchers analyzed NCOR2 expression in 156 epithelial ovarian cancer samples and found a significant correlation with both NCOR2 and GPER expression, particularly in specific histologic subtypes.
  • The results indicate that high levels of both NCOR2 and GPER expression are associated with significantly improved overall survival in ovarian cancer patients, suggesting that nuclear co-repressors like NCOR2 may play a crucial role in cancer prognosis.
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Purpose: The human endometrium consists of different layers (basalis and functionalis) and undergoes different phases throughout the menstrual cycle. In a former paper, our research group was able to describe MSX1 as a positive prognosticator in endometrial carcinomas. The aim of this study was to examine the MSX1 expression in healthy endometrial tissue throughout the different phases to gain more insight on the mechanics of MSX-regulation in the female reproductive system.

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Background: Malignant sex cord-stromal cell tumours (SCST) account for only 7% of ovarian malignancies. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) study group has established a clinicopathological database to provide an overview of the current treatment strategies and survival of SCST patients and to identify research needs.

Methods: Twenty centres provided mixed retro- and prospective data of patients with tumour specimens and second-opinion pathology review treated between 2000 and 2014.

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Mucinous ovarian carcinoma (MOC) is a rare histotype of primary ovarian carcinoma. Frequent pathogenic molecular alterations include mutations in KRAS , TP53 , and overexpression of human epidermal growth factor receptor 2, but without having prognostic relevance. As L1-CAM (cell adhesion molecule) has previously shown prognostic relevance in other epithelial tumors of the female genital tract, we analyzed whether L1-CAM expression affected MOC prognosis.

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The role of progesterone receptor A (PRA) for the survival outcome of cervical cancer patients is ambiguous. In mouse models, it has been shown that PRA plays a rather protective role in cancer development. The aim of this study was to assess its expression by immunohistochemistry in 250 cervical cancer tissue samples and to correlate the results with clinicopathological parameters including patient survival.

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Introduction: This project aimed to identify the frequency of a switch of hormone receptor (HR) and/or HER2 status after neoadjuvant chemotherapy (NAC) for early breast cancer.

Methods: Tumor samples from patients without pathological complete response (non-pCR) were evaluated. Pathological complete response (pCR) was defined as no invasive tumor in breast and lymph nodes (ypT0/is ypN0).

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Article Synopsis
  • * Researchers found that BRCA1 mutant cancer tissues had higher levels of nuclear PAF-AH compared to BRCA1 wild-type (WT) samples, suggesting that PAF-AH may have a protective role in this type of cancer.
  • * Silencing PAF-AH increased cell growth and moved β-catenin to the nucleus, activating the Wnt signaling pathway, indicating that PAF-AH negatively regulates Wnt signaling to potentially protect against tumorigenesis in
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Objective: By loading transfer RNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARS) are essential for protein translation. Both cytosolic ARS1-deficiencies and mitochondrial ARS2 deficiencies can cause severe diseases. Amino acid supplementation has shown to positively influence the clinical course of four individuals with cytosolic ARS1 deficiencies.

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In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping.

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Targeting the tumor-associated carbonic anhydrase XII (CA XII) is considered a promising strategy to improve cancer treatment. As such progress is highly demanded for ovarian carcinomas, the present study aimed to provide deeper information about their CA XII expression profile. A large collection of tissue specimens was stained immunohistochemically with a specific anti-CA XII antibody to evaluate the expression in neoplastic and non-neoplastic epithelial ovarian cells.

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