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Front Endocrinol (Lausanne) ; 12: 714909, 2021.
Article in English | MEDLINE | ID: covidwho-1497067


Background: Clinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis. Methods: The clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB. Results: The bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU). Conclusions: Based on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

COVID-19 , Carcinoma, Endometrioid , Endometrial Neoplasms , Host-Pathogen Interactions , Naphthoquinones/pharmacology , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/genetics , Calcium-Binding Proteins/drug effects , Calcium-Binding Proteins/metabolism , Carcinoma, Endometrioid/complications , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/genetics , Computational Biology , Drug Screening Assays, Antitumor/methods , Endometrial Neoplasms/complications , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Regulatory Networks/drug effects , Genetic Association Studies , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Membrane Proteins/drug effects , Membrane Proteins/metabolism , Middle Aged , Mitogen-Activated Protein Kinase 3/drug effects , Mitogen-Activated Protein Kinase 3/metabolism , Molecular Docking Simulation/methods , Naphthoquinones/therapeutic use , Prognosis , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Signal Transduction/drug effects , Signal Transduction/genetics , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism , Uterus/drug effects , Uterus/metabolism , Uterus/pathology , Uterus/virology
BMJ Open ; 11(7): e050755, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1331813


INTRODUCTION: Postmenopausal bleeding (PMB), the red flag symptom for endometrial cancer, triggers urgent investigation by transvaginal ultrasound scan, hysteroscopy and/or endometrial biopsy. These investigations are costly, invasive and often painful or distressing for women. In a pilot study, we found that voided urine and non-invasive vaginal samples from women with endometrial cancer contain malignant cells that can be identified by cytology. The aim of the DEveloping Tests for Endometrial Cancer deTection (DETECT) Study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB. METHODS AND ANALYSIS: This is a multicentre diagnostic accuracy study of women referred to secondary care with PMB. Eligible women will be asked to provide a self-collected voided urine sample and a vaginal sample collected with a Delphi screener before routine clinical procedures. Pairs of specialist cytologists, blinded to participant cancer status, will assess and classify samples independently, with differences settled by consensus review or involving a third cytologist. Results will be compared with clinical outcomes from standard diagnostic tests. A sample size of 2000 women will have 80% power to establish a sensitivity of vaginal samples for endometrial cancer detection by cytology of ≥85%±7%, assuming 5% endometrial cancer prevalence. The primary objective is to determine the diagnostic accuracy of urogenital samples for endometrial cancer detection by cytology. Secondary objectives include the acceptability of urine and vaginal sampling to women. ETHICS AND DISSEMINATION: This study has been approved by the North West-Greater Manchester West Research Ethics Committee (16/NW/0660) and the Health Research Authority. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via charity websites. TRIAL REGISTRATION NUMBER: ISRCTN58863784.

Diagnostic Tests, Routine , Endometrial Neoplasms , Endometrial Neoplasms/diagnosis , Endometrium , Female , Humans , Pilot Projects , Postmenopause , Ultrasonography , Uterine Hemorrhage/etiology
ESMO Open ; 5(Suppl 3)2020 07.
Article in English | MEDLINE | ID: covidwho-688771


The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines.

Coronavirus Infections/therapy , Genital Neoplasms, Female/therapy , Medical Oncology/methods , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Betacoronavirus/physiology , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Delivery of Health Care/statistics & numerical data , Delivery of Health Care/trends , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/therapy , Europe/epidemiology , Female , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/epidemiology , Humans , Medical Oncology/organization & administration , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/therapy , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Societies, Medical , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/therapy