scholarly journals Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives

2018 ◽  
Vol 7 (4) ◽  
pp. 40 ◽  
Author(s):  
Mariamena Arbitrio ◽  
Maria Teresa Di Martino ◽  
Francesca Scionti ◽  
Vito Barbieri ◽  
Licia Pensabene ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Predictive Biomarkers ◽  
Daily Practice ◽  
Metabolizing Enzymes ◽  
Medical Treatments ◽  
Genes Encoding ◽  
Robust Tests ◽  
The Individual ◽  
Drug Receptors ◽  
Drug Pharmacokinetics

In the past decades, many efforts have been made to individualize medical treatments, taking into account molecular profiles and the individual genetic background. The development of molecularly targeted drugs and immunotherapy have revolutionized medical treatments but the inter-patient variability in the anti-tumor drug pharmacokinetics (PK) and pharmacodynamics can be explained, at least in part, by genetic variations in genes encoding drug metabolizing enzymes and transporters (ADME) or in genes encoding drug receptors. Here, we focus on high-throughput technologies applied for PK screening for the identification of predictive biomarkers of efficacy or toxicity in cancer treatment, whose application in clinical practice could promote personalized treatments tailored on individual’s genetic make-up. Pharmacogenomic tools have been implemented and the clinical utility of pharmacogenetic screening could increase safety in patients for the identification of drug metabolism-related biomarkers for a personalized medicine. Although pharmacogenomic studies were performed in adult cohorts, pharmacogenetic pediatric research has yielded promising results. Additionally, we discuss the current challenges and theoretical bases for the implementation of pharmacogenetic tests for translation in the clinical practice taking into account that pharmacogenomics platforms are discovery oriented and must open the way for the setting of robust tests suitable for daily practice.

ABCB1, CYP3A5*3, and CYP3A4*1B SNPs and risk of toxicity with sunitinib treatment for mRCC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 485-485
Author(s):  
Maria Bassanelli ◽  
Alessandra Felici ◽  
Michele Milella ◽  
Diana Giannarelli ◽  
Silvana Giacinti ◽  
...  
Keyword(s):  
Nucleotide Polymorphisms ◽  
Test Results ◽  
Chi Square ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Genes Encoding ◽  
Hand Foot Syndrome ◽  
Chi Square Test ◽  
Grade 3 ◽  
The Individual

485 Background: Currently there are no biomarkers to predict either toxicity or activity of targeted therapy in mRCC. The aim of this study was to correlate single nucleotide polymorphisms (SNPs) of genes encoding for efflux transporters and metabolizing enzymes with sunitinib toxicity in metastatic renal cell carcinoma (mRCC) patients (pts). Methods: We conducted an observational, retrospective analysis of 60 Caucasian pts who received sunitinib for mRCC from 2 Italian institutions. Correlation between adverse events (AE, according to CTCAE v.4.0) and 4 polymorphisms in 3 genes (ABCB1 [1236C>T, 3435C>T], CYP3A5*3 6986A>G, CYP3A4*1B-392A>G) was analyzed. SNPs were detected in blood samples using pyrosequencing technique. Association between SNPs and toxicities was evaluated using the Chi Square test. Results: 60pts (median age: 61 years; male: 63.3%) with mRCC (clear cell: 85%, other histologies: 15%) were treated with sunitinib (83.3% as first-line). The most common AE (any-grade) reported were: hypertension (85%), asthenia (83.3%), hypothyroidism (65%), anemia (61.6%), nausea/vomiting (60%), stomatitis (58.3%), diarrhoea (48.3%), neutropenia (48.3%), thrombocytopenia (46.7%), leukopenia (46.7%), hypertriglyceridemia (45%), hyperglycaemia (38.4%), hypercholesterolemia (35%), and hand-foot syndrome (35%). Treatment was discontinued and sunitinib dose was reduced due to AE in 28.3% and 61.7% of pts, respectively. The G/A-variant in CYP3A5*3 was associated with thrombocytopenia (any grade, p=0.03); homozygous C/C alleles in ABCB1 1236C>T significantly correlated with leukopenia (any grade, p=0.01), while the C/C genotype in ABCB1 3435C>T was associated with hypertension (grade≥3, p=0.05); hypertriglyceridemia showed a trend towards increased prevalence in the presence of the C allele (grade≥3, p=0.08). Conclusions: Polymorphisms in ABCB1 and CYP3A5*3 are predictive of toxicity, as hypertension, leukopenia, and thrombocytopenia in pts with mRCC treated with sunitinib. This analysis could support the selection of the more appropriate drug to the individual patient.

scholarly journals Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

2021 ◽  
Vol 14 (3) ◽  
pp. 204
Author(s):  
Teresa Iannaccone ◽  
Carmine Sellitto ◽  
Valentina Manzo ◽  
Francesca Colucci ◽  
Valentina Giudice ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Drug Response ◽  
Current Knowledge ◽  
Individual Variability ◽  
Mood Stabilizers ◽  
Drug Metabolizing Enzymes ◽  
Efficacy And Safety ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Drug Pharmacokinetics

Pharmacogenomics can identify polymorphisms in genes involved in drug pharmacokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagnosis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, because their benefit in clinical practice is still controversial. In this review, we summarize the current knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.

scholarly journals POS1391 MEASURING SUBCLINICAL INFLAMMATION IN HAND AND FOREFOOT IN PATIENTS WITH ARTHRALGIA USING 1.5T OR 3.0T MRI: DOES FIELD STRENGTH MATTER?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 978.1-978
Author(s):  
D. Krijbolder ◽  
M. Verstappen ◽  
F. Wouters ◽  
L. R. Lard ◽  
P. D. De Buck ◽  
...  
Keyword(s):  
Field Strength ◽  
Scientific Evidence ◽  
Correlation Coefficients ◽  
Daily Practice ◽  
Scientific Data ◽  
Imaging Features ◽  
Subclinical Inflammation ◽  
The Individual ◽  
3.0T Mri ◽  
Inflammation Score

Background:Magnetic resonance imaging (MRI) of small joints sensitively detects inflammation. MRI-detected subclinical inflammation, and tenosynovitis in particular, has been shown predictive for RA development in patients with arthralgia. These scientific data are mostly acquired on 1.0T-1.5T MRI scanners. However, 3.0T MRI is nowadays increasingly used in practice. Evidence on the comparability of these field strengths is scarce and it has never been studied in arthralgia where subclinical inflammation is subtle. Moreover, comparisons never included tenosynovitis, which is, of all imaging features, the strongest predictor for progression to RA.Objectives:To determine if there is a difference between 1.5T and 3.0T MRI in detecting subclinical inflammation in arthralgia patients.Methods:2968 locations (joints, bones or tendon sheaths) in hands and forefeet of 28 arthralgia patients were imaged on both 1.5T and 3.0T MRI. Two independent readers scored for erosions, osteitis, synovitis (according to RAMRIS) and tenosynovitis (as described by Haavaardsholm et al.). Scores were also summed as total inflammation (osteitis, synovitis and tenosynovitis) and total RAMRIS (erosions, osteitis, synovitis and tenosynovitis) scores. Interreader reliability (comparing both readers) and field strength agreement (comparing 1.5T and 3.0T) was assessed with interclass correlation coefficients (ICCs). Next, field strength agreement was assessed after dichotomization into presence or absence of inflammation. Analyses were performed on patient- and location-level.Results:ICCs between readers were excellent (>0.90). Comparing 1.5 and 3.0T revealed excellent ICCs of 0.90 (95% confidence interval 0.78-0.95) for the total inflammation score and 0.90 (0.78-0.95) for the total RAMRIS score. ICCs for individual inflammation features were: tenosynovitis: 0.87 (0.74-0.94), synovitis 0.65 (0.24-0.84) and osteitis 0.96 (0.91-0.98). The field strength agreement on dichotomized scores was 83% for the total inflammation score and 89% for the total RAMRIS score. Of the individual features, agreement for tenosynovitis was the highest (89%). Analyses on location- level showed similar results.Conclusion:Agreement of subclinical inflammation scores on 1.5T and 3.0T were good to excellent, in particular for tenosynovitis. This suggests that scientific evidence on predictive power of MRI in arthralgia patients, obtained on 1.5T, can be generalized to 3.0T when this field strength would be used for diagnostic purposes in daily practice.Disclosure of Interests:None declared

Polymorphisms in genes encoding interleukin-10 and drug metabolizing enzymes GSTP1, GSTT1, GSTA1 and UGT1A1 influence risk and outcome in Hodgkin lymphoma

2012 ◽  
Vol 53 (10) ◽  
pp. 1934-1944 ◽  
Author(s):  
Olav E. Yri ◽  
Per O. Ekstrøm ◽  
Vera Hilden ◽  
Gustav Gaudernack ◽  
Knut Liestøl ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Interleukin 10 ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Genes Encoding

Group Psychotherapy in Private Practice

1970 ◽  
Vol 4 (1) ◽  
pp. 43-48 ◽  
Author(s):  
George L. Christie
Keyword(s):  
Clinical Practice ◽  
Group Psychotherapy ◽  
Patient Selection ◽  
Private Practice ◽  
Group Leader ◽  
Developmental History ◽  
Individual Form ◽  
Organization And Management ◽  
History Of ◽  
The Individual

Some tentative conclusions about the organization and management of relatively closed psychotherapeutic groups are illustrated by examples culled from private clinical practice. After reviewing the rationale of group psychotherapy and its advantages over the individual form, the paper deals mainly with patient selection, the developmental history of the group and group leader technique.

scholarly journals Recent Advances in the Discovery of Biomarkers for Canine Osteosarcoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Anita K. Luu ◽  
Geoffrey A. Wood ◽  
Alicia M. Viloria-Petit
Keyword(s):  
Clinical Practice ◽  
Standard Treatment ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Future Directions ◽  
Diagnostic Biomarkers ◽  
Canine Osteosarcoma ◽  
The Past ◽  
Biomarker Research

Canine osteosarcoma (OSA) is an aggressive malignancy that frequently metastasizes to the lung and bone. Not only has there been essentially no improvement in therapeutic outcome over the past 3 decades, but there is also a lack of reliable biomarkers in clinical practice. This makes it difficult to discriminate which patients will most benefit from the standard treatment of amputation and adjuvant chemotherapy. The development of reliable diagnostic biomarkers could aid in the clinical diagnosis of primary OSA and metastasis; while prognostic, and predictive biomarkers could allow clinicians to stratify patients to predict response to treatment and outcome. This review summarizes biomarkers that have been explored in canine OSA to date. The focus is on molecular biomarkers identified in tumor samples as well as emerging biomarkers that have been identified in blood-based (liquid) biopsies, including circulating tumor cells, microRNAs, and extracellular vesicles. Lastly, we propose future directions in biomarker research to ensure they can be incorporated into a clinical setting.

The Role of Genetic Data Analysis for Precision Therapy in Cancer

2021 ◽  
pp. 127-143
Author(s):  
Sunishtha Singh Yadav ◽  
Vandana Chauhan ◽  
Vijeta Singh ◽  
Svenja Kohler
Keyword(s):  
Personalized Medicine ◽  
Cancer Susceptibility ◽  
Metabolizing Enzymes ◽  
Specific Patient ◽  
Genome Wide ◽  
Radio Therapy ◽  
Precision Therapy ◽  
Drug Receptors ◽  
Genetic Data Analysis

Cancer has been known as a devastating disease that takes thousands of lives every year. And since this is a heterogenous disease, standard treatments, like chemotherapy, radiation, and chemo-radio therapy, are effective in specific patient population subset only. Genetic differences play a very crucial role in defining cancer susceptibility and also in determining the drug's efficacy by affecting regulation, expression, and activity of drug metabolizing enzymes, drug transporters, and drug receptors. This genetic variability of the disease lends itself to the emerging field of precision or personalized medicine. There are some specific ways of acquiring data for precision or personalized medicine approach like genome wide association scan (GWAS). This is basically identification and scanning of biomarkers throughout the complete DNA/genome of several individuals to study any type of genetic variations which are linked with any form of cancer.

scholarly journals Delivery of a nutritional prescription by enteral tube feeding in children with chronic kidney disease stages 2–5 and on dialysis—clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

2020 ◽  
Vol 36 (1) ◽  
pp. 187-204
Author(s):  
Lesley Rees ◽  
◽  
Vanessa Shaw ◽  
Leila Qizalbash ◽  
Caroline Anderson ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Growth Parameters ◽  
Tube Feeding ◽  
Low Grade ◽  
Enteral Tube Feeding ◽  
Practice Recommendations ◽  
The Individual ◽  
Disease Stages

AbstractThe nutritional prescription (whether in the form of food or liquid formulas) may be taken orally when a child has the capacity for spontaneous intake by mouth, but may need to be administered partially or completely by nasogastric tube or gastrostomy device (“enteral tube feeding”). The relative use of each of these methods varies both within and between countries. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPRs) based on evidence where available, or on the expert opinion of the Taskforce members, using a Delphi process to seek consensus from the wider community of experts in the field. We present CPRs for delivery of the nutritional prescription via enteral tube feeding to children with chronic kidney disease stages 2–5 and on dialysis. We address the types of enteral feeding tubes, when they should be used, placement techniques, recommendations and contraindications for their use, and evidence for their effects on growth parameters. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgement. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.

scholarly journals MULTICAGE CAD-4: Psychometric characteristics for the screening of addictive behaviors

2018 ◽  
Vol 35 (1) ◽  
pp. 41-46
Author(s):  
Mª Teresa Rodríguez Monje ◽  
Eduardo J. Pedrero Pérez ◽  
Mª Teresa Rodríguez Monje ◽  
Elías Rodríguez Alonso ◽  
Elías Rodríguez Alonso ◽  
...  
Keyword(s):  
Health Care ◽  
Primary Health Care ◽  
Health Care Services ◽  
Least Squares Method ◽  
Daily Practice ◽  
Addictive Behaviors ◽  
Care Services ◽  
Primary Health ◽  
Scale Levels ◽  
The Individual

Addictive behaviors are not limited to drugs use, but also include certain daily behaviors that can cause gratification. Their progression to more severe pathological patterns entails grave consequences for the individual, including multiple psychopathological manifestations. The early detection of this type of behavior is of concern to primary health care. Therefore, in order to detect risk at early stages, reliable and valid tools for daily practice are essential. The MULTICAGE CAD-4 questionnaire is a screening tool for simultaneously detecting addictive behaviors. This study includes a new scale for the detection of smartphone abuse. The objective is to evaluate the adequacy of its psychometric properties. A sample of 2,074 subjects that were recruited from primary care centers ofMadrid(Spain) completed the MULTICAGE CAD-4 questionnaire. A confirmatory factor analysis, using unweighted least squares method, was performed. The test showed good internal consistency both at item and scale levels. The questionnaire structure was consistent with theoretical expectations. The MULTICAGE CAD-4, including the new smartphone scale, is a robust, reliable tool with a valid structure for assessing the presence of dysfunctional or potentially addictive behaviors, and especially useful in primary health care services.

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