scholarly journals An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target

2018 ◽  
Vol 25 (12) ◽  
pp. R647-R662 ◽  
Author(s):  
A Coopes ◽  
C E Henry ◽  
E Llamosas ◽  
C E Ford

Endometrial cancer is the most common gynaecological malignancy in developed nations, and its prevalence is rising as women defer or decide not to have children and as obesity rises, both key risk factors. Despite this, treatment options remain limited, particularly for advanced or refractory disease. New genomic analyses have revealed distinct mutational profiles with therapeutic and prognostic potential. Wnt signalling, which is pivotal in embryogenesis, healing and homeostasis, is of importance in the endometrium and has been linked to carcinogenesis. This review aims to update and discuss the current evidence for the role of β-catenin dependent and independent Wnt signalling, including the ROR receptors in the endometrium and its potential as a therapeutic target, in light of recent trials of Wnt-targeted therapy in multiple tumour types.

2014 ◽  
Vol 40 (2) ◽  
pp. 301-311 ◽  
Author(s):  
Giorgio Bogani ◽  
Sean C. Dowdy ◽  
William A. Cliby ◽  
Fabio Ghezzi ◽  
Diego Rossetti ◽  
...  

2011 ◽  
Vol 13 (6) ◽  
pp. 472-478 ◽  
Author(s):  
Carien L. Creutzberg ◽  
Remi A. Nout

2021 ◽  
Vol 22 (17) ◽  
pp. 9136
Author(s):  
Amanda Kornel ◽  
Danja J. Den Hartogh ◽  
Panagiota Klentrou ◽  
Evangelia Tsiani

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.


2020 ◽  
Vol 26 (4) ◽  
pp. 586-602 ◽  
Author(s):  
J Maia ◽  
BM Fonseca ◽  
N Teixeira ◽  
G Correia-da-Silva

Abstract BACKGROUND The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation. OBJECTIVE AND RATIONALE In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment. SEARCH METHODS Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia; endocannabinoid system and endometrial cancer; endocannabinoid system and reproduction; endocannabinoid, endometrium; placenta; N-acylethanolamines; anandamide; 2-arachidonoylglycerol; and cannabinoids. OUTCOMES This review demonstrates relevant information concerning ECS alterations in endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. We highlight the importance of the endocannabinoids in endometrial and placental physiology and pathophysiology, from studies in vitro and in vivo and in clinical observations. The most studied of the endogenous cannabinoids is AEA. The levels of AEA were increased in plasma of patients with endometriosis and miscarriage, as well as in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial cancer. Changes in the pattern of expression of the cannabinoid receptor CB1 were also observed in endometrial biopsies of endometriosis, fallopian tube and decidua of patients with ectopic pregnancy and pre-eclamptic placenta. Moreover, alterations in CB2 expression have been reported in association with endometrial cancer. In general, studies on the cannabinoid signalling through CB2 and on the biological activities of the other major endocannabinoid, namely 2-AG, as well as its metabolic enzymes are scarce and avidly required. WIDER IMPLICATIONS The pathophysiological mechanisms involved in the described endometrial and placental pathologies are still unclear and lack the means for an early diagnosis. Based on current evidence, though alterations in ECS are demonstrated at tissue level, it is difficult to associate plasmatic changes in AEA with specific endometrial and placental diseases. Thus, pairing alterations in AEA levels with 2-AG and/or other endocannabinoid-like molecules may provide more accurate and early diagnoses. In addition, patients may benefit from new therapies that target the ECS and endocannabinoid signalling.


2021 ◽  
Vol 22 (5) ◽  
pp. 2305
Author(s):  
Futaba Inoue ◽  
Kenbun Sone ◽  
Yusuke Toyohara ◽  
Yu Takahashi ◽  
Asako Kukita ◽  
...  

Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.


2021 ◽  
Vol 8 ◽  
Author(s):  
Kavya L. Singampalli ◽  
Elysa Jui ◽  
Kevin Shani ◽  
Yao Ning ◽  
Jennifer P. Connell ◽  
...  

Congenital heart disease (CHD) poses a significant global health and economic burden—despite advances in treating CHD reducing the mortality risk, globally CHD accounts for approximately 300,000 deaths yearly. Children with CHD experience both acute and chronic cardiac complications, and though treatment options have improved, some remain extremely invasive. A challenge in addressing these morbidity and mortality risks is that little is known regarding the cause of many CHDs and current evidence suggests a multifactorial etiology. Some studies implicate an immune contribution to CHD development; however, the role of the immune system is not well-understood. Defining the role of the immune and inflammatory responses in CHD therefore holds promise in elucidating mechanisms underlying these disorders and improving upon current diagnostic and treatment options. In this review, we address the current knowledge coinciding CHDs with immune and inflammatory associations, emphasizing conditions where this understanding would provide clinical benefit, and challenges in studying these mechanisms.


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
K Pufal ◽  
A Lawson ◽  
J Hodson ◽  
M Bangash ◽  
J Patel ◽  
...  

Abstract Aim Post hepatectomy liver failure (PHLF) is a rare but serious complication following liver resection. PHLF is associated with high mortality of up to 50% in severe cases. With limited treatment options available, there is a need to evaluate the role of systems that support the function of the liver as treatment modalities following PHLF development. Method The aim of this study was to review the literature and summarise the role of liver support systems (LSS) in the management of PHLF. Publications of interest were identified using systematically designed searches. Following screening, data from the relevant publications were extracted, pooled where possible, and analysed. Results Systematic review identified ten studies, which used either Plasma Exchange (PE) or Molecular Adsorbent Recirculating System (MARS) as LSS after PHLF development. The sample sizes of included studies were small, ranging from N = 2 to N = 13. Across all studies, the pooled 90-day mortality rate was 40% (95% CI: 15% - 68%). However, there was substantial heterogeneity (I2=64%), likely since the studies used a variety of definitions for PHLF and had different selection criteria for patient eligibility for LSS treatment. Conclusions Despite potential benefits, the current evidence is insufficient to recommend LSS for the routine management of severe PHLF, with the current literature consisting of only a limited number of studies. There is a definite need for larger, multicentre, prospective studies evaluating the conventional and newer modalities of support systems with a view to improve the outcomes in this group of patients.


2021 ◽  
Vol 23 (9) ◽  
pp. 823-833
Author(s):  
Mirja C Nolff

Practical relevance: Open wounds and their treatment present a common challenge in veterinary practice. Approaching 15 years ago negative pressure wound therapy (NPWT) started to be incorporated into clinical veterinary medicine, and its availability is becoming more widespread in Europe and the USA. Use of this therapy has the potential to significantly increase the healing rate of open wounds as well as free skin grafts in small animals, and it has been occasionally described for the management of feline wounds. Aim: This review describes the mechanisms of action of, and indications for, NPWT, and offers recommendations for NPWT specific to feline patients. Evidence base: The information presented is based on the current evidence and the author’s clinical experience of the technique gained over the past 12 years. Comparative studies of different treatment options are lacking and, since wound healing in cats and dogs differs, cat-specific studies are especially needed. Well-designed wound healing studies comparing different advanced techniques will improve open wound healing in cats in the future, and potentially allow better understanding of the role of NPWT in this setting.


Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 107 ◽  
Author(s):  
Maria Scherma ◽  
Paolo Masia ◽  
Matteo Deidda ◽  
Walter Fratta ◽  
Gianluigi Tanda ◽  
...  

Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated.


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