Identification of Potent EGFR Inhibitors from TCM Database@Taiwan

Overexpression of epidermal growth factor receptor (EGFR) has been associated with cancer. Targeted inhibition of the EGFR pathway has been shown to limit proliferation of cancerous cells. Hence, we employed Traditional Chinese Medicine Database (TCM Database@Taiwan) (http://tcm.cmu.edu.tw) to identify potential EGFR inhibitor. Multiple Linear Regression (MLR), Support Vector Machine (SVM), Comparative Molecular Field Analysis (CoMFA), and Comparative Molecular Similarities Indices Analysis (CoMSIA) models were generated using a training set of EGFR ligands of known inhibitory activities. The top four TCM candidates based on DockScore were 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid, and all had higher binding affinities than the control Iressa®. The TCM candidates had interactions with Asp855, Lys716, and Lys728, all which are residues of the protein kinase binding site. Validated MLR (r² = 0.7858) and SVM (r² = 0.8754) models predicted good bioactivity for the TCM candidates. In addition, the TCM candidates contoured well to the 3D-Quantitative Structure-Activity Relationship (3D-QSAR) map derived from the CoMFA (q² = 0.721, r² = 0.986) and CoMSIA (q² = 0.662, r² = 0.988) models. The steric field, hydrophobic field, and H-bond of the 3D-QSAR map were well matched by each TCM candidate. Molecular docking indicated that all TCM candidates formed H-bonds within the EGFR protein kinase domain. Based on the different structures, H-bonds were formed at either Asp855 or Lys716/Lys728. The compounds remained stable throughout molecular dynamics (MD) simulation. Based on the results of this study, 2-O-caffeoyl tartaric acid, Emitine, Rosmaricine, and 2-O-feruloyl tartaric acid are suggested to be potential EGFR inhibitors.National Science Council of Taiwan (NSC 99-2221-E-039-013-)Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030)China Medical University (CMU98-TCM)China Medical University (CMU99-TCM)China Medical University (CMU99-S-02)China Medical University (CMU99-ASIA-25)China Medical University (CMU99-ASIA-26)China Medical University (CMU99-ASIA-27)China Medical University (CMU99-ASIA-28)Asia UniversityTaiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Arabic validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)

Introduction and hypothesis: Our aim was to translate then assess the reliability of the culturally adapted Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire, International Urogynecological Association (IUGA)-Revised (PISQ-IR) to assess sexual health among Arabic-speaking women with pelvic floor disorders. Methods: PISQ-IR was modified to consider cultural characteristics of the Middle East. The final reliability study included 172 women with urinary incontinence (UI) and/or pelvic organ prolapse (POP). Participants completed the questionnaire twice: at enrollment and 2 weeks later. Results: Among sexually active women, good internal consistency was observed for five of the six scales in the adapted instrument: Global Quality (Cronbach’s coefficient α = 0.86), Condition Impact (α = 0.87), Desire (α = 0.82), Condition Specific (α = 0.74), and Partner Related (α = 0.75). Internal consistency was acceptable for the Arousal Orgasm subscale (α = 0.66). However, among not sexually active women, internal consistency was poor (α <0.6) for all four scales. Lin’s concordance correlation coefficient measuring agreement between test and retest measurements [Lin’s concordance correlation coefficient (CCC); a value of 1 represents perfect agreement] ranged from 0.81 to 0.87 for the not sexually active scales, except for condition impact (CCC = 0.63.) For sexually active women, CCC was typically stronger, ranging from 0.85 to 0.96. Conclusions: PISQ-IR questionnaire is easy to administer and reliable for assessing sexual function in sexually active Arabic women with POP and UI, but internal consistency is poor for Arabic women not sexually active

Arabic validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)

Introduction and hypothesis: Our aim was to translate then assess the reliability of the culturally adapted Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire, International Urogynecological Association (IUGA)-Revised (PISQ-IR) to assess sexual health among Arabic-speaking women with pelvic floor disorders. Methods: PISQ-IR was modified to consider cultural characteristics of the Middle East. The final reliability study included 172 women with urinary incontinence (UI) and/or pelvic organ prolapse (POP). Participants completed the questionnaire twice: at enrollment and 2 weeks later. Results: Among sexually active women, good internal consistency was observed for five of the six scales in the adapted instrument: Global Quality (Cronbach’s coefficient α = 0.86), Condition Impact (α = 0.87), Desire (α = 0.82), Condition Specific (α = 0.74), and Partner Related (α = 0.75). Internal consistency was acceptable for the Arousal Orgasm subscale (α = 0.66). However, among not sexually active women, internal consistency was poor (α <0.6) for all four scales. Lin’s concordance correlation coefficient measuring agreement between test and retest measurements [Lin’s concordance correlation coefficient (CCC); a value of 1 represents perfect agreement] ranged from 0.81 to 0.87 for the not sexually active scales, except for condition impact (CCC = 0.63.) For sexually active women, CCC was typically stronger, ranging from 0.85 to 0.96. Conclusions: PISQ-IR questionnaire is easy to administer and reliable for assessing sexual function in sexually active Arabic women with POP and UI, but internal consistency is poor for Arabic women not sexually active

Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: Molecular docking studyDesign, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: Molecular docking study

: Novel derivatives of quinazoline (1-27) have been synthesized and tested for their antitumor activity against three tumor cell lines among these cell lines the human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. All tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC50 range of 3.35-6.81 mu g/ml. With regarding broad-spectrum activity compounds 5, 9, 15, 18 and 20 exploited potent antitumor against human liver cell line (HEPG2), human breast cell line (MCF-7) and human cervix cell line (HELA) with IC50 range of 3.35-5.59 mu g/ml. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors. (C) 2010 Elsevier Masson SAS. All rights reserved