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Current Oncology (Toronto, Ont.) Oct 2022Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast... (Review)
Review
Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast cancer is of primary urgency, as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor involved in the regulation of neuronal functions through the binding of the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). In addition, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin, or by binding to TrkA receptors with low affinity. Several examples of in vitro and in vivo evidence show that NGF is both synthesized and released by breast cancer cells, and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. In this paper, we comprehensively summarize and systematically review the current experimental evidence on this topic. INPLASY ID: INPLASY2022100017.
Topics: Female; Humans; Nerve Growth Factor; Receptor, trkA; Breast Neoplasms; Receptor, Nerve Growth Factor; Signal Transduction
PubMed: 36354700
DOI: 10.3390/curroncol29110640 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Journal of Neural Transmission (Vienna,... Apr 2022The serotonergic system is implicated in ADHD, but the impact of serotonin's precursor molecule, tryptophan, on ADHD symptomology remains unclear. Systematic searches of... (Review)
Review
The serotonergic system is implicated in ADHD, but the impact of serotonin's precursor molecule, tryptophan, on ADHD symptomology remains unclear. Systematic searches of randomised controlled trials with an experimental tryptophan intervention in children and adults with ADHD identified 14 studies measuring core and related symptoms of the condition. Risk of bias was assessed using the Cochrane Risk of Bias tool. The 14 studies all used acute tryptophan depletion procedures, and most did not investigate core ADHD symptoms (inattention, impulsivity, hyperactivity) as primary outcome measures. Only two studies examined attention and revealed mixed effects of tryptophan. Similar effects were found for impulsivity in a small number of studies. No studies investigated hyperactivity. Most studies focused on reactive aggression, but samples were heterogenous and small, rendering potential meta-analyses inconclusive or misleading. However, the narrative analysis indicates tryptophan interventions may impact reactive aggression. More research is needed on the effect of tryptophan modulation on core ADHD symptoms, especially in adults, using more diverse samples to determine potential as an intervention. From current data, tryptophan modulation appears to alter aggressive behaviour in ADHD; however, the available studies were insufficient for the planned meta-analysis.
Topics: Adult; Aggression; Attention Deficit Disorder with Hyperactivity; Child; Humans; Impulsive Behavior; Tryptophan
PubMed: 35286460
DOI: 10.1007/s00702-022-02478-5 -
PloS One 2022There are on-going debates about what is and is not 'mindfulness'. These debates are stifling rigorous academic research as scientific precision is a precursor to shared... (Meta-Analysis)
Meta-Analysis Review
There are on-going debates about what is and is not 'mindfulness'. These debates are stifling rigorous academic research as scientific precision is a precursor to shared meaning. While mindfulness is a growing field of research, these divergent and conflated meanings are limiting deeper interdisciplinary research. Interventions designed in one practice context may not be useful in other contexts because meaning is not transferred between settings. This review clarifies the various research domains that study mindfulness and the conceptual and operational definitions in each domain. This two-stage study comprises a scoping review of mindfulness classifications and a comparative content mapping of mindfulness studies from 2015 to 2021. The initial comprehensive search strategy followed the preferred reporting items for scoping reviews and meta-analysis (PRISMA) method. The comparative analysis was conducted using Leximancer. Findings illustrate a complex growing research corpus on mindfulness that is somewhat confused. The results from the scoping review show three shared domains in mindfulness classifications: short-term effects of mindfulness, long-term effects of mindfulness, and mindfulness practices. The results from the content mapping show four domains of mindfulness research: mental health, behavioural change, cognitive neuroscience, and ethical mindfulness. Operational definitions of mindfulness are not articulated clearly in these domains. Conceptual and operational definitions in the 'ethical mindfulness' domain are not yet developed. To enhance scientific progress in mindfulness research, further investigations of mindfulness classifications need to be developed. Content mapping and semantic typology is a potential candidate for future classification. More attention should be paid to developing operational definitions according to specific research domains. Scholars in the ethical mindfulness domain will need solid conceptual and operational definitions to support their research efforts.
Topics: Mindfulness; Research Design
PubMed: 35507587
DOI: 10.1371/journal.pone.0264924 -
Antioxidants (Basel, Switzerland) Nov 2022Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH)... (Review)
Review
Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH) neutralizes ROS, although it is consumed. NAC is a precursor of GSH synthesis, and administering an appropriate dose of NAC to patients with respiratory conditions may enhance lung recovery and replenish GSH. The present review searched for articles reporting on the effects of NAC in TB treatment from 1960 to 31 May 2022. The PICO search strategy was used in Google Scholar, PubMed, SciFinder, and Wiley online library databases. The COVIDENCE tool was used to delete inappropriate content. We eventually discovered five clinical trials, one case report, seven reviews, in vitro research, and four experimental animal studies from the twenty-four accepted articles. The use of NAC resulted in increased GSH levels, decreased treatment time, and was safe with minimal adverse events. However, the evidence is currently insufficient to estimate the overall effects of NAC, thus the study warrants more NAC clinical trials to demonstrate its effects in TB treatment.
PubMed: 36421484
DOI: 10.3390/antiox11112298 -
Blood Jun 2023The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear,... (Meta-Analysis)
Meta-Analysis
The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing the frequency of vincristine-steroid pulses during maintenance for pediatric patients newly diagnosed with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from 25 publications (12 513 patients), and assessed the risk of bias. We created historical and contemporary subgroups; the latter included trials providing both a version of Protocol III from the early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.85-1.09), which differed significantly from historical trials (HR, 0.79; 95% CI, 0.68-0.91; P = .04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however increased odds of grade 3+ nonhepatic toxicity in the high-pulse frequency group (odds ratio, 1.31; 95% CI, 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide the development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance among patients not in clinical trials, particularly those experiencing toxicity.
Topics: Humans; Child; Vincristine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adrenal Cortex Hormones; Steroids; Progression-Free Survival; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36821772
DOI: 10.1182/blood.2022018899 -
PloS One 2022The COVID-19 pandemic has prompted governments around the globe to implement various restriction policies, including lockdown, social distancing, and school closures....
AIM
The COVID-19 pandemic has prompted governments around the globe to implement various restriction policies, including lockdown, social distancing, and school closures. Subsequently, there has been a surge in sedentary behaviour particularly screen time (ST) together with a significant decline in physical activity that was more marked amongst children and adolescents. Excessive screen exposure in adolescents has been correlated with cardio-metabolic risk factors including obesity, hypertension, high cholesterol, and glucose intolerance that may have adverse morbidity and mortality implications in adulthood. Thus, the current study aimed to synthesize the literature on the relationship between ST of various types and the risk of metabolic syndrome (MetS) in adolescents in the context of the COVID-19 pandemic.
METHODS
In August 2021, a systematic search of the literature was undertaken using electronic databases: PubMed, PsycINFO, and the Cochran library. Studies were considered if they met the following key eligibility criteria: (i) Measure of ST as an exposure (TV, computer, videogames, internet, smartphone, tablet), using quantified duration/frequency either self-reported or observed; (ii) Measure of MetS as an outcome with standard definition and/or criteria required to establish MetS diagnosis. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the risk of bias.
RESULTS
A total of ten studies met the inclusion criteria, and the majority were cross sectional studies. Most studies met fair bias scoring. Overall, the review revealed considerable evidence that suggests a significant negative association between ST and components of MetS among adolescents with dose-response association.
CONCLUSION
During the pandemic, screen usage may become more prevalent through periods of school closures, lockdowns, social isolation, and online learning classes. Public health policies and health promotion strategies targeting parents are needed to raise awareness of the adverse health effects associated with screen-based sedentary behaviour as a precursor of NCDs. Parent or home focused interventions might be effective in limiting adolescents' screen exposure, alternatively substituted with an appropriate level of physical activity.
PROSPERO REGISTRATION NUMBER
PROSPERO 2021 CRD42021272436.
Topics: Adolescent; COVID-19; Communicable Disease Control; Exercise; Female; Humans; Male; Metabolic Syndrome; Screen Time; Sedentary Behavior
PubMed: 35312701
DOI: 10.1371/journal.pone.0265560 -
Scientific Reports Jan 2024Cardiac magnetic resonance (CMR) is the gold standard for the diagnostic classification and risk stratification in most patients with cardiac disorders. The aim of the... (Meta-Analysis)
Meta-Analysis
Cardiac magnetic resonance (CMR) is the gold standard for the diagnostic classification and risk stratification in most patients with cardiac disorders. The aim of the present study was to investigate the ability of Strain-encoded MR (SENC) for the prediction of major adverse cardiovascular events (MACE). A systematic review and meta-analysis was performed according to the PRISMA Guidelines, including patients with or without cardiovascular disease and asymptomatic individuals. Myocardial strain by HARP were used as pulse sequences in 1.5 T scanners. Published literature in MEDLINE (PubMed) and Cochrane's databases were explored before February 2023 for studies assessing the clinical utility of myocardial strain by Harmonic Phase Magnetic Resonance Imaging (HARP), Strain-encoded MR (SENC) or fast-SENC. In total, 8 clinical trials (4 studies conducted in asymptomatic individuals and 4 in patients with suspected or known cardiac disease) were included in this systematic review, while 3 studies were used for our meta-analysis, based on individual patient level data. Kaplan-Meier analysis and Cox proportional hazard models were used, testing the ability of myocardial strain by HARP and SENC/fast-SENC for the prediction of MACE. Strain enabled risk stratification in asymptomatic individuals, predicting MACE and the development of incident heart failure. Of 1332 patients who underwent clinically indicated CMR, including SENC or fast-SENC acquisitions, 19 patients died, 28 experienced non-fatal infarctions, 52 underwent coronary revascularization and 86 were hospitalized due to heart failure during median 22.4 (17.2-28.5) months of follow-up. SENC/fast-SENC, predicted both all-cause mortality and MACE with high accuracy (HR = 3.0, 95% CI = 1.2-7.6, p = 0.02 and HR = 4.1, 95% CI = 3.0-5.5, respectively, p < 0.001). Using hierarchical Cox-proportional hazard regression models, SENC/fast-SENC exhibited incremental value to clinical data and conventional CMR parameters. Reduced myocardial strain predicts of all-cause mortality and cardiac outcomes in symptomatic patients with a wide range of ischemic or non-ischemic cardiac diseases, whereas in asymptomatic individuals, reduced strain was a precursor of incident heart failure.
Topics: Humans; Magnetic Resonance Imaging, Cine; Heart; Magnetic Resonance Imaging; Heart Diseases; Heart Failure; Magnetic Resonance Spectroscopy; Predictive Value of Tests; Prognosis
PubMed: 38212323
DOI: 10.1038/s41598-023-50835-5 -
Dermatology (Basel, Switzerland) 2021Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology...
BACKGROUND
Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology and pathogenesis of HS are unclear and gene mutations might play a role.
SUMMARY
The primary focus of the review is on aggregating the gene mutations reported, summarizing the structure of γ-secretase and analyzing and speculating about the mechanism and the underlying relations between gene mutation and functional changes of protein. The systematic literature review was done by searching the PubMed, Embase, and Web of Science databases. γ-Secretase is an intramembrane protease complex responsible for the intramembranous cleavage of more than 30 type-1 transmembrane proteins including amyloid precursor protein and Notch receptors. The protein complex consists of four hydrophobic proteins: presenilin, presenilin enhancer-2 (PSENEN), nicastrin, and anterior pharynx defective 1 (APH1). To date, 57 mutations of γ-secretase genes have been reported in 70 patients or families worldwide, including 39 in NCSTN, 14 in PSENEN, and 4 in PSEN1, of which 17 are frameshifts, 15 result in nonsense mutations, 13 in missense mutations, and 12 are splice site mutations. Given the structure of γ-secretase and analysis of related mutation loci of NCSTN, PSENEN, and PSEN1, mutations in γ-secretase genes could affect activation of presenilin, prevent substrate binding, and hinder intramembrane cleavage of select proteins.
Topics: Amyloid Precursor Protein Secretases; Hidradenitis Suppurativa; Humans; Mutation
PubMed: 33333507
DOI: 10.1159/000512455 -
Technology in Cancer Research &... 2023Gastric cancer is the fourth deadliest cancer worldwide. Due to the lack of specific early symptoms and noninvasive methods for early detection, the prognosis of... (Review)
Review
Gastric cancer is the fourth deadliest cancer worldwide. Due to the lack of specific early symptoms and noninvasive methods for early detection, the prognosis of gastric cancer patients is poor. Gastric cancer has a well-recognized infectious etiology, with and Epstein-Barr Virus being the main associated infectious agents. Although other Epstein-Barr Virus-associated malignancies often manifest with abnormal levels of anti-Epstein-Barr Virus antibodies, it is not clear whether this is also true for gastric cancer. Potentially, these antibodies could serve as a noninvasive tool for gastric cancer screening or as markers for gastric cancer risk and provide a better understanding of the participation of Epstein-Barr Virus in the development of this neoplasm. We conducted a systematic review of articles analyzing anti-Epstein-Barr Virus serology in gastric cancer and precursor lesions following PRISMA guidelines. Patients were classified according to the Correa cascade of gastric lesions and whether they were positive or negative by EBER- hybridization (Epstein-Barr Virus-associated gastric cancer and Epstein-Barr Virus-nonassociated gastric cancer, respectively). We retrieved 16 articles involving 9735 subjects from 12 different countries and 4 databases, PubMed, SciELO, Scopus, and Google Scholar. Higher antibody titers were observed not only in Epstein-Barr Virus-associated gastric cancer than in Epstein-Barr Virus-nonassociated gastric cancer but also in Epstein-Barr Virus-nonassociated gastric cancer and gastric cancer-precursor lesions when compared with patients with mild dyspepsia or healthy controls. In all cases, the associations were predominantly with antibodies directed against lytic cycle antigens. Data support the role of Epstein-Barr Virus lytic reactivation in the development of advanced gastric lesions. However, more studies are needed to confirm these associations, particularly the association with lesions considered negative by EBER- hybridization, and to establish a set of antibodies and thresholds indicative of enhanced risk to develop these lesions.
Topics: Humans; Herpesvirus 4, Human; Stomach Neoplasms; Risk
PubMed: 37078150
DOI: 10.1177/15330338231169875