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1.
Inflamm Res ; 71(10-11): 1159-1167, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35941297

RESUMO

INTRODUCTION: Fenofibrate is an agonist of peroxisome proliferator activated receptor alpha (PPAR-α), that possesses anti-inflammatory, antioxidant, and anti-thrombotic properties. Fenofibrate is effective against a variety of viral infections and different inflammatory disorders. Therefore, the aim of critical review was to overview the potential role of fenofibrate in the pathogenesis of SARS-CoV-2 and related complications. RESULTS: By destabilizing SARS-CoV-2 spike protein and preventing it from binding angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 entry, fenofibrate can reduce SARS-CoV-2 entry in human cells Fenofibrate also suppresses inflammatory signaling pathways, which decreases SARS-CoV-2 infection-related inflammatory alterations. In conclusion, fenofibrate anti-inflammatory, antioxidant, and antithrombotic capabilities may help to minimize the inflammatory and thrombotic consequences associated with SARSCoV-2 infection. Through attenuating the interaction between SARS-CoV-2 and ACE2, fenofibrate can directly reduce the risk of SARS-CoV-2 infection. CONCLUSIONS: As a result, fenofibrate could be a potential treatment approach for COVID-19 control.


Assuntos
Tratamento Farmacológico da COVID-19 , Fenofibrato , Trombose , Humanos , Enzima de Conversão de Angiotensina 2 , SARS-CoV-2 , Fenofibrato/uso terapêutico , Antioxidantes/metabolismo , Peptidil Dipeptidase A/metabolismo , Ligação Proteica
2.
Sci Rep ; 9(1): 17405, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31757986

RESUMO

Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.


Assuntos
Biologia Computacional/métodos , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias/etiologia , Oncogenes , Biomarcadores Tumorais , Exoma , Ontologia Genética , Estudos de Associação Genética/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Aprendizado de Máquina , Anotação de Sequência Molecular , Mutação , Neoplasias/diagnóstico , Curva ROC
3.
PLoS One ; 14(7): e0219093, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291302

RESUMO

This cross-sectional study is aimed at assessing the quality of life in a cohort of breast cancer patients at the Oncology Department, King Abdulaziz University Hospital (KAUH), King Abdulaziz University (KAU), Jeddah, Saudi Arabia (SA), and to differentiate QoL among different groups. Mean time since diagnosis was 3.97±1.90 years. European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 and BR23 (EORTC QLQ-C30 & BR23) were used to assess QoL in breast cancer survivors. ANOVA and independent t-test (parametric tests) were used for the categorical variables and Kruskal-Wallis and Mann-Whitney tests used for non-parametric tests. Linear regression analysis was done to measure predictors' significance and to calculate the coefficient of determination. Two hundred and eighty-four patients completed the survey. Global health status and functional scales, in most of the domains, were high, while symptom scales were moderate-to-low for most items, showing better QoL. Insomnia and fatigue were the most disturbing symptoms. Patients exhibited higher scores for body image and future perspective, while the least score is for sexual functioning. Global health, physical functioning, and role functioning were better in the age group ≤50 years (p<0.05). Premenopausal and perimenopausal patients showed a better level of functioning as compared to postmenopausal patients (p = 0.001). Premenopausal patients scored higher for sexual enjoyment, as compared to peri- and post-menopausal patients (p = 0.04). Systemic therapy side effects were more evident in the breast conservative surgery group. Predictors explained 8% of the variation in Physical functioning (R-squared = 0.08). A predictor that had a remarkable influence on physical functioning, as compared to the other predictors in the model, was menopausal status (P = 0.02). So, it was concluded that the breast cancer patients visiting our institute had a better quality of life regarding overall global health status as well as functional and symptom scales. Some issues, for instance, fatigue, insomnia, hair loss, and others, warrant good supportive therapy.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Fadiga/psicologia , Qualidade de Vida/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Adulto , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/psicologia , Pré-Menopausa/psicologia , Psicometria , Análise de Regressão , Arábia Saudita , Inquéritos e Questionários , Centros de Atenção Terciária
4.
Oncotarget ; 9(29): 20282-20293, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29755651

RESUMO

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.

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