New insights into the functions of progesterone receptor (PR) isoforms and progesterone signaling

xlomafota13 shared this article with you from Inoreader New insights into the functions of progesterone receptor (PR) isoforms and progesterone signaling Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5214-5232. eCollection 2021. ABSTRACT Progesterone, the ovarian steroid hormone, regulates a plentitude of biological processes in tissues ranging from the brain to bones. Recognizing the role of progesterone and its receptors in physiological processes and maladies can prevent and treat various diseases. Apart from its physiological functions, its role in developing diseases, especially breast cancer, is a recent topic of deliberation. There exists conflicting experimental and epidemiological evidence linking progesterone to breast cancer. This review tries to describe the physiological functions of progesterone and its receptors, genomic and non-genomic signaling, splice variants, and a different aspect of progesterone signaling. Furthermore, we seek to address or attempt to discuss the following pertinent questions on steroid hormone signaling; How does progesterone influence breast cancer progres sion? How does it change the molecular pathways in breast cancer with different receptor statuses, the specific role of each isoform, and how does the ER/and PR ratio affect progesterone signaling? PMID:34873457 | PMC:PMC8640821 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment

xlomafota13 shared this article with you from Inoreader DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5644-5658. eCollection 2021. ABSTRACT Esophageal carcinoma (EC) is one of the most pervasive cancers in the world, with upwards of 500,000 new diagnoses, annually. Despite its prominence, advancements in the detection and treatment of EC have been marginal over the past 30 years and the survival rate continues to stay below 20%. This is due to the uncommonly heterogeneous presentation of EC which presents unprecedented challenges in improving patient survival and quality of care. However, distinct epigenetic alterations to the DNA methylome may provide an avenue to drastically improve the detection and treatment of EC. Specifically, the creation of novel biomarker panels that consist of EC-specific methylation markers have shown promise as a potential alternative to the more invasive, contemporary diagnostic methods. Additionally, growing insight into the biological and clinical properties of EC-spec ific methylation patterns have opened a window of opportunity for enhanced treatment; of growing interest is the application of "DNMT inhibitors" - a class of drugs which inhibit excessive methylation and have been shown to re-sensitize chemoresistant tumors. Here we provide a comprehensive review of the current advancements in EC DNA methylation to underscore a potential approach to its detection and treatment. PMID:34873485 | PMC:PMC8640794 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Development of KAM score to predict metastasis and worse survival in breast cancer

xlomafota13 shared this article with you from Inoreader Development of KAM score to predict metastasis and worse survival in breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5388-5401. eCollection 2021. ABSTRACT Some may think that prediction of metastasis is meaningless since metastatic breast cancer is currently incurable. We argue that effective identification of developing metastasis will enable us to design and conduct clinical trials specifically targeting those patients at high risk. The current study sought to generate the KAM score by 4 genes (BRSK2, EYA1, SIGLEC15, and AGTR1) overexpressed in primary breast cancer that developed metastasis to bone compared with matched controls without metastasis longer than 10 years. A high KAM score was prognostic of poor overall (OS), disease free survival (DFS), and disease specific survival (DSS) in the METABRIC, and OS in the GSE96058 cohorts. A high KAM score was significantly associated with clinical aggressiveness, such as high American Joint Committee Cancer (AJCC) stage, lymph node metastasis, Nottingha m pathological grade, and triple negative breast cancer (TNBC). Subgroup analysis revealed that a high KAM score was associated with worse OS in ER-positive/HER2-negative breast cancer in both cohorts. A high KAM breast cancer enriched all 5 cell proliferation-related gene sets of the Hallmark collection and interferon (IFN)-γ response gene sets. Furthermore, a high KAM breast cancer was significantly infiltrated with a high fraction of not only anti-cancer but also pro-cancer immune cells and associated with high level of cytolytic activity. Finally, a high KAM breast cancer was significantly associated with lung metastasis. In conclusion, we developed KAM score using 4 gene expressions that predict lung metastasis and patient survival in breast cancer. PMID:34873467 | PMC:PMC8640803 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.