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.

m6A methyltransferase METTL3 promotes oral squamous cell carcinoma progression through enhancement of IGF2BP2-mediated SLC7A11 mRNA stability

xlomafota13 shared this article with you from Inoreader m<sup>6</sup>A methyltransferase METTL3 promotes oral squamous cell carcinoma progression through enhancement of IGF2BP2-mediated SLC7A11 mRNA stability Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5282-5298. eCollection 2021. ABSTRACT As the key enzyme of the N6-methyladenosine (m6A) in eukaryotic messenger RNA, METTL3 plays an important role in tumor progression, but the exact mechanism by which METTL3 controls oral squamous cell carcinoma (OSCC) progression remains unclear. In this study, METTL3 expression in OSCC samples was analyzed by qPCR and immunohistochemistry. The effects of METTL3 suppression on OSCC cell lines were measured by CCK-8, Ki67 flow cytometry analysis, invasion transwell and wound healing assays. MeRIP-seq and RNA-seq analyses were performed to explore target gene of METTL3. RIP-qPCR and RNA stability assays were performed to explore the mechanism by which METTL3 regulated the target genes. Triptolide was used to evaluate its specific treatment effects on METTL3 in OSCC cells. BALB/c nude mice were used to establish orthotopic and subcutaneous xenograft models to verify the in vitro results. The results showed that METTL3 was upregulated in OSCC tissues compared with OSCC adjacent normal tissues, and its expression was associated with T stage, lymphatic metastasis and prognosis. METTL3 suppression impaired OSCC cells proliferation, invasion, and migration. MeRIP-seq and RNA-seq analysis identified that SLC7A11 mRNA was the m6A target of METTL3, which was verified by meRIP-qPCR, qPCR and western blot. METTL3 depletion decreased the stability of SLC7A11 mRNA, and IGF2BP2 as m6A reader was involved in this process. Moreover, METTL3 knockdown attenuated the binding between SLC7A11 mRNA and IGF2BP2, finally leading to accelerate SLC7A11 mRNA degradation. Triptolide inhibited METTL3-mediated SLC7A11 expression, thus suppressing malignancy of OSCC cells. In conclusion, the new finding of the manuscript is that METTL3 enhances the mRNA stability of SLC7A11 via m6A-mediated binding of IGF2BP2, which thus pr omotes OSCC progression, and triptolide inhibits OSCC by suppressing METTL3-SLC7A11 axis. Triptolide has a potential to be as an effective anti-OSCC drug targeted to METTL3. PMID:34873461 | PMC:PMC8640804 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.

Morphometric analysis of the lumbar vertebrae and intervertebral discs in relation to abdominal aorta: CT-based study

xlomafota13 shared this article with you from Inoreader Morphometric analysis of the lumbar vertebrae and intervertebral discs in relation to abdominal aorta: CT-based study Via radiol anat Surg Radiol Anat. 2021 Dec 7. doi: 10.1007/s00276-021-02865-9. Online ahead of print. ABSTRACT PURPOSE: Although lumbar discectomy is the most common procedure in spine surgery, reports about anatomical relations between discs and prevertebral vessels are limited. Aim of this research was to investigate morphometric of the lumbar region and the relations between intervertebral discs (IVDs) and abdominal aorta. METHODS: 557 abdominal computed tomography scans were assess ed. For each spinal column level from Th12/L1 down to L4/L5, we investigated: intervertebral disc's and vertebra's height, width, length, and distance from aorta or common iliac artery (CIA). Those arteries were also measured in two dimensions and classified based on location. RESULTS: 54.58% of patients were male. There was a significant difference in arterial-disc distances (ADDs) between genders at the levels: L1/L2 (1.32 ± 1.97 vs. 0.96 ± 1.78 mm; p = 0.0194), L2/L3 (1.97 ± 2.16 vs. 1.15 ± 2.01 mm; p < 0.0001), L3/L4 (2.54 ± 2.78 vs. 1.71 ± 2.61 mm; p = 0.0012), also for both CIAs (left CIA 3.64 ± 3.63 vs. 2.6 ± 3.06 mm; p = 0.0004 and right CIA: 7.96 ± 5.06 vs. 5.8 ± 4.57 mm; p < 0.001)-those ADDs were higher in men at all levels. The length and width of IVD increased alongside with disc level with the maximum at L4/L5. CONCLUSION: Bifurcations of the aorta in most cases occurred at the L4 level. Collected data suggest that at the highest lumbar leve ls, there is a greater possibility to cause injury of the aorta due to its close anatomical relationship with discs. Females have limited, in comparison to males, ADD at L1/L2, L2/L3, and L3/L4 levels what should be taken into consideration during preoperative planning of surgical intervention. PMID:34874459 | DOI:10.1007/s00276-021-02865-9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exoscopic visualisation with VITOM® 3D in paediatric cochlear implantation: preliminary results

xlomafota13 shared this article with you from Inoreader Exoscopic visualisation with VITOM® 3D in paediatric cochlear implantation: preliminary results Via Clinical Otolaryngology Abstract 3D exoscopy is an emerging visualisation technique designed to improve ergonomics and image quality during surgeries. We present a novel application of the VITOM® 3D exoscope in cochlear implantation (IDEAL Stage 2a prospective case series). The system enabled high-quality visualisation during both posterior tympanotomy and electrode insertion. Both the chief surgeon and the staff members rated the ergonomics of the system highly. 3D exoscopy is a useful alternative to conventional microscopy, but the two techniques remain to be directly compared in larger studies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization

xlomafota13 shared this article with you from Inoreader Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization Via Melanoma Research - Published Ahead-of-Print Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which seru m MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen deprivation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis. * Jaeseob Lee and Young-June Jin contributed equally to the writing of this article. Received 29 March 2021 Accepted 22 September 2021 Correspondence to Hansoo Lee, PhD, Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea, Tel: +82 33 250 8530; e-mail: hslee@kangwon.ac.kr Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.