Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data.

Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events.

MTHFR polymorphisms and capecitabine-induced toxicity in patients with metastatic colorectal cancer.

Objective: The availability of current chemotherapeutic options for metastatic colorectal cancer (mCRC) has increased survival, but it is also accompanied by considerable morbidity. Fluoropyrimidines are the mainstay of systemic therapy. Germline pharmacogenetic markers involved in 5-fluorouracil pharmacodynamics could provide individualized pretreatment tools for predicting toxicity.

Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using low-dose methotrexate.

Low-dose methotrexate (MTX) is part of the mainstay of rheumatoid arthritis treatment. Hepatotoxicity is among the most feared side effects of low-dose MTX and is associated with increased morbidity. At present, histological evaluation of liver biopsies is the gold standard to retrospectively diagnose MTX-induced liver damage.

Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis.

Background: Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment.

Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction.

Background: Antiplatelet drug resistance is a well-known problem, causing recurrent cardiovascular events. Multiple genetic polymorphisms have been related to antiplatelet resistance by several large trials, however data from common clinical practice is limited. We examined the influence of previously described polymorphisms, related to aspirin and clopidogrel resistance, on treatment outcome in a real life unselected population of patients presenting with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention.

Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure.

Background: The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied.

Methods: For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.

Population pharmacokinetics and pharmacogenetics of everolimus in renal transplant patients.

Background And Objective: Everolimus is a novel macrolide immunosuppressant used in the prevention of acute and chronic rejection of solid organ transplants. Everolimus is being actively investigated worldwide as a non-nephrotoxic alternative for calcineurin inhibitors. Its highly variable pharmacokinetics and narrow therapeutic window make it difficult to maintain an adequate exposure to prevent serious adverse effects.

Lapatinib for advanced or metastatic breast cancer.

Lapatinib is a potent reversible and selective inhibitor of the tyrosine kinase domains of epidermal growth factor receptor and human epidermal growth factor receptor (HER)-2 that exerts its action by competitive binding to the intracellular ATP-binding site of the receptor. It is registered for the treatment of advanced or metastatic HER-2+ breast cancer in combination with capecitabine and for hormone receptor-positive breast cancer in combination with an aromatase inhibitor. Lapatinib administered orally once daily is moderately to well tolerated, with rash and gastrointestinal adverse events as the main toxicities.

Efficiency and mechanism of antigen-specific CD8+ T-cell activation using synthetic long peptides.

Synthetic long peptides that contain immunogenic T-cell epitopes have been used to induce activation of antigen-specific CD8 T cells in vitro for immune monitoring or adoptive transfer, or in vivo after peptide vaccination. However, the efficiency and mechanisms of presentation of exogenous long peptides in human leukocyte antigen (HLA) class I remain to be elucidated. In this study, we demonstrated that the efficiency of antigen-specific CD8 T-cell activation using extended peptide variants of common viral epitopes is variable.

Phenotyping drug disposition in oncology.

Efficacy and toxicity of anticancer agents are highly variable between patients and variation in drug disposition is thought to be an important determinant. Genetics, physiology, and environment all are underlying factors contributing to this variation. Phenotyping drug metabolizing enzymes and drug transporters by using in vivo probes is a method that can be used to individualize drug therapy.

Differences in 5-hydroxytryptamine-3B haplotype frequencies between Asians and Caucasians.

Background: The 5-hydroxytryptamine (5-HT3) receptor is a ligand-operated ion channel with five different receptor subunits (5-HT3A, B, C, D, and E) found in humans. Activation of 5-HT3 receptors influences various effects such as drug-induced emesis and causes behavioral problems such as anxiety, depression and cognitive disorders. To explore interethnic differences in the response to 5-HT3 antagonists, we studied haplotype frequencies in the gene encoding the 5-HT3B receptor in Asians and Caucasians.

Impact of chemotherapy-induced nausea and vomiting on quality of life in indonesian patients with gynecologic cancer.

Background: Quality of life (QoL) has become a major outcome in the treatment of patients with cancer. This study is aimed at examining the impact of chemotherapy-induced nausea and vomiting on QoL of patients with gynecologic cancer in Indonesia.

Methods: Chemotherapy-naive patients with gynecologic cancer, who were treated with cisplatin at a dosage 50 mg/m or higher as monotherapy or as part of combination chemotherapy regimens, were recruited in the Oncology Department, Dr.

Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis.

Objective: The contribution of low-penetrance single nucleotide polymorphisms to methotrexate efficacy in rheumatoid arthritis (RA) is inconsistent between studies. We sought to elucidate architecture of methotrexate response in three cohorts of patients with RA treated with methotrexate.

Methods: Single nucleotide polymorphism frequencies in genes from folate, purine, and pyrimidine pathways were measured to develop a model of gene-gene interactions using multifactor dimensionality reduction in 439 patients who received methotrexate in the USA and The Netherlands.

Alternative methods to a TaqMan assay to detect a tri-allelic single nucleotide polymorphism rs757210 in the HNF1β gene.

Background: Several studies report difficulties in genotyping HNF1β rs757210 using TaqMan probes. This is possibly due to the tri-allelic nature of this single nucleotide polymorphism (SNP). The aim of the present research was to develop alternative methods for genotyping rs757210.

Liposomal drug formulations in cancer therapy: 15 years along the road.

Liposomes as pharmaceutical drug carriers were developed to increase antitumour efficacy and decrease drug toxicity. Doxorubicin HCl liposomal injection was the first liposomal encapsulated anticancer drug to receive clinical approval. To date, virtually all traditional anticancer drugs have been encapsulated in liposomes.

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Objective: Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Methods: We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m(2) as monotherapy or as combined chemotherapy.

A systematic review on pharmacogenetics in cardiovascular disease: is it ready for clinical application?

Pharmacogenetics is the search for heritable genetic polymorphisms that influence responses to drug therapy. The most important application of pharmacogenetics is to guide choosing agents with the greatest potential of efficacy and smallest risk of adverse drug reactions. Many studies focusing on drug-gene interactions have been published in recent years, some of which led to adaptation of FDA recommendations, indicating that we are on the verge of the clinical application of genetic information in drug therapy.

Activation of tumor-promoting type 2 macrophages by EGFR-targeting antibody cetuximab.

Purpose: In a recent randomized phase III clinical trial in metastatic colorectal cancer patients, the addition of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) cetuximab to bevacizumab and chemotherapy resulted in decreased progression-free survival, in particular for patients with the high-affinity FcγRIIIA.

Experimental Design: The presence of natural killer (NK) cells and type 2 (M2) macrophages in colorectal cancer was determined by immunohistochemistry, using antibodies to lineage-specific markers NKp46 and CD68 with CD163, respectively. Influence of tumor-bound cetuximab on M2 macrophages was carried out in vitro with EGFR-expressing tumor cells and short-term differentiated monocytes from blood donors, who were typed for the FcγRIIIA polymorphism (CD16).

Dopamine agonists and ischemic complications in Parkinson's disease: a nested case-control study.

Background: It has been suggested that ergoline dopamine agonists can cause ischemic complications. The effect of dopamine agonists in general on the prevalence of ischemic events in patients with Parkinson's disease (PD) has not been studied.

Objective: Our aim was to investigate the association between the use of dopamine agonists and hospitalization due to ischemic events in patients with PD.

Concordance of predictive markers for EGFR inhibitors in primary tumors and metastases in colorectal cancer: a review.

Background: Currently, only Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status is used as a decisional marker for epidermal growth factor receptor (EGFR) inhibitor therapy in colorectal cancer (CRC) patients. Concordance of KRAS status between primary tumors and metastases has always been considered to be close to perfect; however, cases of discordance have been reported. The actual rate of concordance of KRAS status remains unclear, as is the same for v-raf murine sarcoma viral oncogene homolog B1 (BRAF), phosphatidylinositol 3-kinase CA subunit (PIK3CA), and loss of phosphatase and tensin homologue deleted on chromosome ten (PTEN).

Genetic risk factors for type 2 diabetes mellitus and response to sulfonylurea treatment.

Objective: After the identification of type 2 diabetes mellitus (T2DM) risk alleles from genome-wide association studies, models have been developed to identify subjects at high risk to develop T2DM. We hypothesize that a panel of 20 repeatedly associated T2DM risk alleles influences response to sulfonylureas (SUs).

Methods: Two hundred and seven incident SU (tolbutamide, glibenclamide, glimepiride, gliclazide) users with T2DM were recruited from four primary care centers.