Aim: We studied the influence of coffee consumption on the therapeutic effect of methotrexate (MTX) in patients with rheumatoid arthritis (RA) sorted according to ADORA2A genotypes. Patients & methods: 82 RA patients were dichotomized according to caffeine intake with a threshold of 700 mg/week. Disease activity score 28 (DAS28) was applied (>3.2: high; <3.2: low or remission). Patients were genotyped using quantitative PCR allelic discrimination. Results: We found significantly higher risk of RA in patients with higher caffeine intake and the CT genotype of ADOARA2A rs2298383, rs3761422 and rs2267076 SNPs. The CC genotype of ADORA2A rs2236624 SNP in patients with lower caffeine intake treated with MTX is significantly protective. Conclusion:ADORA2A genotypes and coffee intake influence risk of RA and efficacy of it MTX treatment.
- MeSH
- adenosin genetika metabolismus MeSH
- antirevmatika metabolismus terapeutické užití MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus genetika MeSH
- káva škodlivé účinky metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- methotrexát metabolismus terapeutické užití MeSH
- průřezové studie MeSH
- receptor adenosinový A2A genetika MeSH
- revmatoidní artritida farmakoterapie genetika metabolismus MeSH
- signální transdukce účinky léků fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.
Pancreatic carcinoma is usually diagnosed late when treatment options are limited and is considered a chemo-resistant malignancy. However, early stage, good performance status and specific patient subgroup are thought to have a more favorable prognosis. Search for novel molecular biomarkers, which could predict treatment resistance, represents a major opportunity, but also a challenge in further research. This review summarizes most aspects of individualized therapy of pancreatic cancer including promising biomarkers, BRCA-deficient pancreatic cancer and its etiology. It may be estimated that nearly a third of metastatic pancreatic ductal adenocarcinoma patients could benefit from treatment other than gold standard chemotherapy. Thus, other aspects of an individualized approach concerning the main factors for the choice of the best therapy for individual pancreatic cancer patient (surgery and chemotherapy), as well as the future directions (target therapy and immunotherapy), are also addressed.
- MeSH
- adenokarcinom farmakoterapie genetika imunologie patologie MeSH
- chemorezistence genetika imunologie MeSH
- cílená molekulární terapie MeSH
- imunoterapie MeSH
- individualizovaná medicína * MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory slinivky břišní farmakoterapie genetika imunologie patologie MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- signální transdukce účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
DNA repair, a complex biological process, ensures genomic integrity. Alterations in DNA repair, occurring in many cancers, contribute to the accumulation of mutations in the genome, resulting in genomic instability and cancer progression. DNA repair also plays a substantial role in response to chemotherapeutics: rapidly dividing colon cancer cells, vulnerable to DNA-damaging agents and overcoming DNA repair, undergo cell death. DNA repair capacity represents a complex biomarker, integrating gene variants, gene expressions, the stability of gene products, the effect of inhibitors/stimulators, lifestyle and environmental factors. Here, we discuss DNA repair capacity in sporadic colon cancer, a frequent malignancy worldwide, in relation to tumor heterogeneity, prognosis and prediction, measurements in surrogate and target tissues and suggest important tasks to be addressed.
- MeSH
- buněčná smrt účinky léků MeSH
- epigeneze genetická genetika MeSH
- lidé MeSH
- mutace MeSH
- nádory tračníku farmakoterapie genetika patologie MeSH
- nestabilita genomu účinky léků genetika MeSH
- oprava DNA účinky léků MeSH
- poškození DNA účinky léků MeSH
- prognóza MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).
- MeSH
- haplotypy * MeSH
- individualizovaná medicína MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- methotrexát * MeSH
- revmatoidní artritida MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
Colorectal cancer is a common type of malignant disease with high rates of morbidity and mortality. Although treatment options have been expanded over the last years, the mainstay of curative treatment remains surgical removal of the tumor-bearing organ. Systemic treatment options include classic cytotoxic drugs as well as some biological agents. Noncoding RNAs are an evolving field in cancer diagnosis, prognosis and possible treatment. Noncoding miRNAs are small molecules with huge impact on gene expression. They have been a substantial part of cancer research for more than a decade. In this review article, the current knowledge of miRNAs and colorectal cancer diagnosis, prognosis and novel or evolving therapeutic concepts are discussed. Examples of how miRNAs might change the management of the disease will be described.
- MeSH
- antitumorózní látky aplikace a dávkování terapeutické užití MeSH
- cílená molekulární terapie MeSH
- kolorektální nádory farmakoterapie genetika MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádorové biomarkery genetika MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIM: To provide pharmacogenomics reporting guidelines, the information and tools required for reporting to public omic databases. MATERIAL & METHODS: For effective DMET data interpretation, sharing, interoperability, reproducibility and reporting, we propose the Minimum Information required for a DMET Experiment (MIDE) reporting. RESULTS: MIDE provides reporting guidelines and describes the information required for reporting, data storage and data sharing in the form of XML. CONCLUSION: The MIDE guidelines will benefit the scientific community with pharmacogenomics experiments, including reporting pharmacogenomics data from other technology platforms, with the tools that will ease and automate the generation of such reports using the standardized MIDE XML schema, facilitating the sharing, dissemination, reanalysis of datasets through accessible and transparent pharmacogenomics data reporting.
- MeSH
- farmakogenetika * MeSH
- interpretace statistických dat MeSH
- lidé MeSH
- šíření informací MeSH
- výzkumný projekt * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Genetic variants affecting statin uptake, metabolism or predisposing to muscular diseases may confer susceptibility to statin-induced myopathy. Besides the SLCO1B1 rs4149056 genotype, common genetic variants do not seem to determine statin-associated myopathy. Here we aimed to address the potential role of rare variants. METHODS: We performed whole exome sequencing in 88 individuals suffering from statin-associated myopathy and assessed the burden of rare variants using candidate-gene and exome-wide association analysis. RESULTS: In the novel candidate gene CLCN1, we identified a heterozygote truncating mutation p.R894* in four patients. In addition, we detected predictably pathogenic case-specific variants in MYOT, CYP3A5, SH3TC2, FBXO32 and RBM20. CONCLUSION: These findings support the role of rare variants and nominate loci for follow-up studies.
- MeSH
- celogenomová asociační studie MeSH
- chloridové kanály genetika MeSH
- dospělí MeSH
- exom genetika MeSH
- genetická variace MeSH
- genotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci svalů chemicky indukované epidemiologie genetika MeSH
- polypeptid C přenášející organické anionty genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- statiny škodlivé účinky MeSH
- vzácné nemoci genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population. METHODS: The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis. RESULTS: We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.4965C>T and g.4994G>T), one intronic variant (c.1899-20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared with wild-type. CONCLUSION: New POR variant identification indicates the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYP450s in the endoplasmic reticulum. Original submitted 15 September 2014; Revision submitted 17 November 2014.
- MeSH
- DNA genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická variace MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus * MeSH
- kinetika MeSH
- kohortové studie MeSH
- konformace proteinů MeSH
- lidé MeSH
- missense mutace MeSH
- molekulární modely MeSH
- novorozenec MeSH
- sekvence nukleotidů MeSH
- substituce aminokyselin MeSH
- systém (enzymů) cytochromů P-450 chemie genetika metabolismus MeSH
- vazebná nerovnováha MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
Nucleoside analogs such as gemcitabine and 5-fluorouracil are currently the cornerstone of chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Decreased drug transport into tumor cells that may be caused by low expression of membrane proteins, such as solute carrier transporters, represents one of the principal mechanisms of chemotherapy resistance. Individual diversity of multidrug resistance is the major challenge limiting the success of anticancer treatment. Novel biomarkers and pharmacogenomic approaches could further optimize treatment algorithms leading to better survival and lower treatment toxicity in PDAC patients. In this review, the most promising predictive biomarkers from the solute carrier transporter family of membrane transporters and the potential applications for PDAC therapy with nucleoside analogues are summarized.
- MeSH
- adenokarcinom farmakoterapie genetika patologie MeSH
- chemorezistence genetika MeSH
- deoxycytidin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- farmakogenetika * MeSH
- fluorouracil aplikace a dávkování škodlivé účinky MeSH
- lidé MeSH
- membránové transportní proteiny genetika MeSH
- nádory slinivky břišní farmakoterapie genetika patologie MeSH
- polymorfismus genetický MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
