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Pilegaard posted an update 8 months, 3 weeks ago
This study provides new insights into lncRNAs in endocrine-resistant breast cancer.Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFβ, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 (SRD5A1) expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). SRD5A1 expression had the highest general predictive value for clinical benefit and positive predictive value (PPV 85.7%). selleck chemicals AR PAS had the highest negative predictive value (NPV 93.3%). The fitting of a multivariable model led to the identification of SRD5A1, TGFβ, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high SRD5A1 expression were also of prognostic importance regarding PFS and SRD5A1 expression levels for OS. AR, Notch PAS, and SRD5A1 expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients’ treatment.The diagnosis of a myeloid neoplasm relies on a combination of clinical, morphological, immunophenotypic and genetic features, and an integrated, multimodality approach is needed for precise classification. The basic diagnostics of myeloid neoplasms still rely on cell counts and morphology of peripheral blood and bone marrow aspirate, flow cytometry, cytogenetics and bone marrow trephine biopsy, but particularly in the setting of Ph- myeloproliferative neoplasms (MPN), the trephine biopsy has a crucial role. Nowadays, molecular studies are of great importance in confirming or refining a diagnosis and providing prognostic information. All myeloid neoplasms of chronic evolution included in this review, nowadays feature the presence or absence of specific genetic markers in their diagnostic criteria according to the current WHO classification, underlining the importance of molecular studies. Crucial differential diagnoses of Ph- MPN are the category of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2, and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). This review focuses on morphological, immunophenotypical and molecular features of BCR-ABL1-negative MPN and their differential diagnoses. Furthermore, areas of difficulties and open questions in their classification are addressed, and the persistent role of morphology in the area of molecular medicine is discussed.Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients’ quality of life, as well.Uveal melanoma metastases are lethal and remain incurable. A quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary uveal melanoma (pUM) was pursued for insights into UM metastasis and protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology. LC MS/MS iTRAQ technology, the Mascot search engine, and the UniProt human database were used to identify and quantify pUM proteins relative to the normal choroid excised from UM donor eyes. The determined proteomes of all 100 tumors were very similar, encompassing a total of 3935 pUM proteins. Proteins differentially expressed (DE) between metastasizing and non-metastasizing pUM (n = 402) were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. The immune proteins (n = 778) identified in this study support the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as possible candidates for immune therapy checkpoint blockade. Prediction modeling identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy, supporting the potential for protein-based prognostic methods for detecting UM metastasis.Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.