RESUMEN
Pharmacogenomics (PGx) is the hope for the full optimization of drug therapy while minimizing the accompanying adverse drug events that cost billions of dollars annually. Since years before the century, it has been known that inter-individual variations contribute to differences in specific drug responses. It is the bridge to what is well-known today as "personalized medicine". Addressing the drug's pharmacokinetics and pharmacodynamics is one of the features of this science, owing to patient characteristics that vary on so many occasions. Mainly in the liver parenchymal cells, intricate interactions between the drug molecules and enzymes family of so-called "Cytochrome P450" occur which hugely affects how the body will react to the drug in terms of metabolism, efficacy, and safety. Single nucleotide polymorphisms, once validated for a transparent and credible clinical utility, can be used to guide and ensure the succession of the pharmacotherapy plan. Novel tools of pharmacoeconomics science are utilized extensively to assess cost-effective pharmacogenes preceding the translation to the bedside. Drug development and discovery incorporate a drug-gene perspective and save more resources. Regulations and laws shaping the clinical PGx practice can be misconceived; however, these pre-/post approval processes ensure the product's safety and efficacy. National and international regulatory agencies seek guidance on maintaining conduct in PGx practice. In this patient-centric era, social and legal considerations manifest in a way that makes them unavoidable, involving patients and other stakeholders in a deliberate journey toward utmost patient well-being. In this comprehensive review, we contemporarily addressed the scientific leaps in PGx, along with various challenges that face the proper implementation of personalized medicine in Egypt. These informative insights were drawn to serve what the Egyptian population, in particular, would benefit from in terms of knowledge and know-how while maintaining the latest global trends. Moreover, this review is the first to discuss various modalities and challenges faced in Egypt regarding PGx, which we believe could be used as a pilot piece of literature for future studies locally, regionally, and internationally.
RESUMEN
Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.
[Box: see text].
Asunto(s)
Antibacterianos , Monitoreo de Drogas , Vancomicina , Humanos , Vancomicina/uso terapéutico , Monitoreo de Drogas/métodos , Niño , Femenino , Masculino , Antibacterianos/uso terapéutico , Preescolar , Medicina de Precisión/métodos , Adolescente , Neoplasias/tratamiento farmacológico , Egipto , Lactante , Oncología Médica/métodos , Administración del Tratamiento FarmacológicoRESUMEN
Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.
RESUMEN
Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long intergenic non-coding RNA (lncRNA) located on chr11q13. It is overexpressed in several cancers and controls gene expression through chromatin modification, transcriptional regulation, and post-transcriptional regulation. Importantly, MALAT-1 stimulates cell proliferation, migration, and metastasis and serves a vital role in driving the epithelial-to-mesenchymal transition (EMT), subsequently acquiring cancer stem cell-like properties and developing drug resistance. MALAT-1 modulates EMT by interacting with various intracellular signaling pathways, notably the phosphoinositide 3-kinase (PI3K)/Akt and Wnt/ß-catenin pathways. It also behaves like a sponge for microRNAs, preventing their interaction with target genes and promoting EMT. In addition, we have used bioinformatics online tools to highlight the disparities in the expression of MALAT-1 between normal and cancer samples using data from The Cancer Genome Atlas (TCGA). Furthermore, the intricate interplay of MALAT-1 with several essential targets of cancer progression and metastasis renders it a good candidate for therapeutic interventions. Several innovative approaches have been exploited to target MALAT-1, such as short hairpin RNAs (shRNAs), antisense oligonucleotides (ASOs), and natural products. This review emphasizes the interplay between MALAT-1 and EMT in modulating cancer metastasis, stemness, and chemoresistance in different cancers.
RESUMEN
Prostate cancer (PCa) is the most prevalent cancer among men and is the second leading cause of cancer-related death in the United States [...].
RESUMEN
Prostate cancer (PCa) constitutes a significant cause of mortality, with over 37,000 new deaths each year [...].
RESUMEN
Cancer resistance to treatment is very common, represents one of the most significant challenges in the last few decades, and continues to impede all efforts to cure cancer [...].
RESUMEN
PURPOSE: Prostate cancer (PCa) is the second leading cause of cancer death among men in the USA. The emergence of resistance to androgen deprivation therapy gives rise to metastatic castration-resistant prostate cancer. Eprinomectin (EP) is a member of a family of drugs called avermectins with parasiticide and anticancer properties. The pupose of this study was to evaluate the anticancer effects of EP against metastatic PCa using cellular models. METHODS: In this study, we have investigated the effect of EP's anticancer properties and delineated the underlying mechanisms in the DU145 cellular model using several assays such as cell viability assay, colony formation assay, wound-healing assay, immunofluorescence, apoptosis assay, cell cycle analysis, and immunoblotting. RESULTS: Our results indicate that EP significantly inhibits the cell viability, colony formation, and migration capacities of DU145 cells. EP induces cell cycle arrest at the G0/G1 phase, apoptosis via the activation of different caspases, and autophagy through the increase in the generation of reactive oxygen species and endoplasmic reticulum stress. In addition, EP downregulates the expression of cancer stem cell markers and mediates the translocation of ß-catenin from the nucleus to the cytoplasm, indicating its role in inhibiting downstream target genes such as c-Myc and cyclin D1. CONCLUSION: Our study shows that EP has tremendous potential to target metastatic PCa cells and provides new avenues for therapeutic approaches for advanced PCa.
Asunto(s)
Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Ivermectina/farmacología , Ivermectina/uso terapéutico , beta Catenina/metabolismo , Antagonistas de Andrógenos/uso terapéutico , Línea Celular Tumoral , Transducción de Señal , Proliferación Celular , Apoptosis , FenotipoRESUMEN
Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Surgery, radiation therapy, chemotherapy, and androgen deprivation therapy are currently the standard treatment options for PCa. These have poor outcomes and result in the development of castration-resistant prostate cancer (CRPC), which is the foremost underlying cause of mortality associated with PCa. Taxanes, diterpene compounds approved to treat hormonal refractory PCa, show poor outcomes in CRPC. Polygodial (PG) is a natural sesquiterpene isolated from water pepper (Persicaria hydropiper), Dorrigo pepper (Tasmannia stipitata), and mountain pepper (Tasmannia lanceolata). Previous reports show that PG has an anticancer effect. Our results show that PG robustly inhibits the cell viability, colony formation, and migration of taxane-resistant CRPC cell lines and induces cell cycle arrest at the G0 phase. A toxicity investigation shows that PG is not toxic to primary human hepatocytes, 3T3-J2 fibroblast co-cultures, and non-cancerous BPH-1 cells, implicating that PG is innocuous to healthy cells. In addition, PG induces oxidative stress and activates apoptosis in drug-resistant PCa cell lines. Our mechanistic evaluation by a proteome profiler-human apoptotic array in PC3-TXR cells shows that PG induces upregulation of cytochrome c and caspase-3 and downregulation of antiapoptotic markers. Western blot analysis reveals that PG activates apoptotic and DNA damage markers in PCa cells. Our results suggest that PG exhibits its anticancer effect by promoting reactive oxygen species generation and induction of apoptosis in CRPC cells.
RESUMEN
Licorice (Glycyrrhiza glabra) is a well-known natural herb used to treat different ailments since ancient times. Glycyrrhizin (GL), which is the primary triterpenoid compound of licorice extract, has been known to have broad-spectrum pharmacological effects. GL is cleaved into glucuronide and the aglycone, glycyrrhetinic acid (GA), which exists in two stereoisomeric forms: 18α- and 18ß-GA. It is well documented that GL and GA have great potential as anti-inflammatory, anticancer, antiviral, anti-diabetic, antioxidant, and hepatoprotective agents. Studies undertaken during the coronavirus disease 2019 pandemic suggest that GL is effective at inhibiting the viral replication of severe acute respiratory syndrome coronavirus 2. The anticancer effects of GL and GA involve modulating various signaling pathways, such as the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B pathway, the mitogen-activated protein kinase, and the mammalian target of rapamycin/signal transducer and activator of transcription 3, which are mainly involved in regulating cancer cell death, oxidative stress, and inflammation. The potential of GL and GA in preventing cancer development and suppressing the growth and invasion of different cancer types has been reviewed in this paper. This review also provides molecular insights on the mechanism of action for the oncopreventive and oncotherapeutic effects of GL and its derivative, GA, which could help develop more specific forms of these agents for clinical use.
Asunto(s)
Antineoplásicos , COVID-19 , Glycyrrhiza , Triterpenos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/uso terapéutico , Humanos , Fitoquímicos , Extractos Vegetales , Triterpenos/farmacología , Triterpenos/uso terapéuticoRESUMEN
BACKGROUND: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. OBJECTIVE: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. OUR APPROACH: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. ONGOING ACTIVITIES: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. CONCLUSION: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.
RESUMEN
PURPOSE: Worldwide, in the last decade, the numbers of new HIV infections and AIDS-related deaths have drastically decreased. Despite that, around 18 million infected individuals receive antiretroviral therapy and thus tend to live longer. This cross-sectional study was conducted to assess the level of HIV-related knowledge among undergraduate dental students at Ain Shams University (ASU) in Cairo, Egypt and to determine their attitudes toward treating HIV-positive patients. METHODS: The study sample included 247 undergraduate dental students of third, fourth, and fifth academic years at the Faculty of Dentistry, ASU who were randomly selected to participate in this survey. Data were collected using a self-administrated anonymous questionnaire. Chi square and ANOVA tests were used to measure differences in the level of knowledge and attitudes among students of the 3 years. Multiple linear regression analysis was performed with 95% confidence interval. RESULTS: Within the students' population, around 94% incorrectly considered dentists to be at high risk of acquiring HIV infection and 47% believed that saliva is a vehicle for its transmission. Moreover, the majority of students were unaware of the association between HIV and common oral manifestations such as oral candida, Kaposi sarcoma, and leukoplakia. Although 69% of the students were willing to deliver oral care to people living with HIV (PLHIV), only 33% perceived themselves knowledgeable enough to do so. CONCLUSION: Dental students were not adequately prepared to recognize and manage HIV-positive individuals. Thus, better education and training are required to raise their levels of HIV-related knowledge and enhance their capabilities to treat PLHIV.
RESUMEN
Women's relative lack of decision-making power and their unequal access to employment, finances, education, basic health care, and other resources are considered to be the root causes of their ill-health and that of their children. The main purpose of this paper is to examine the interactive relation between women's empowerment and the use of maternal health care. Two model specifications are tested. One assumes no correlation between empowerment and antenatal care while the second specification allows for correlation. Both the univariate and the recursive bivariate probit models are tested. The data used in this study is EDHS 2008. Factor Analysis Technique is also used to construct some of the explanatory variables such as the availability and quality of health services indicators. The findings show that women's empowerment and receiving regular antenatal care are simultaneously determined and the recursive bivariate probit is a better approximation to the relationship between them. Women's empowerment has significant and positive impact on receiving regular antenatal care. The availability and quality of health services do significantly increase the likelihood of receiving regular antenatal care.